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Sample records for phenylketonuria pku development

  1. Phenylketonuria (PKU): A problem solved?

    PubMed

    Brown, Christine S; Lichter-Konecki, Uta

    2016-03-01

    Phenylketonuria (PKU) is a rare metabolic disorder characterized by impaired conversion of phenylalanine (Phe) to tyrosine. If left untreated, the resultant accumulation of excess blood Phe can cause physiological, neurological, and intellectual disabilities. The National PKU Alliance (NPKUA) conducted a survey of its membership to assess current health status and interest in new treatments for PKU. Of the 625 survey respondents, less than half (46.7%) reported blood Phe within (120-360 μmol/L) - the range recommended by the American College of Medical Genetics and Genomics (ACMG). The survey results also showed that younger (≤ 18 years) individuals were about 3-times as successful in keeping their blood Phe concentrations within the recommended clinical range compared with adults. Blood Phe over 360 μmol/L was reported in one-quarter (25.5%) of ≤ 18 year old individuals and almost two-thirds (61.5%) of adults. A little more than half (51.7%) of respondents reported having difficulty in managing their PKU, including the maintenance of a Phe-restricted diet. Individuals with PKU desire new treatments that would allow them to increase their intake of natural protein, discontinue or reduce their intake of medical foods (medical formula and foods modified to be low in protein), improve their mental health (including a reduction in depression and anxiety), and a reduction of their blood Phe concentrations. Respondents preferred oral administration of any newly developed therapies and, in general, disliked therapeutic injections. Injections at home were preferred over injections at a clinic. Payers, government agencies, clinicians, and industry partners should consider patient input when developing and approving new therapies and treatments for PKU. PMID:27014571

  2. Phenylketonuria (PKU): A problem solved?

    PubMed Central

    Brown, Christine S.; Lichter-Konecki, Uta

    2015-01-01

    Phenylketonuria (PKU) is a rare metabolic disorder characterized by impaired conversion of phenylalanine (Phe) to tyrosine. If left untreated, the resultant accumulation of excess blood Phe can cause physiological, neurological, and intellectual disabilities. The National PKU Alliance (NPKUA) conducted a survey of its membership to assess current health status and interest in new treatments for PKU. Of the 625 survey respondents, less than half (46.7%) reported blood Phe within (120–360 μmol/L) — the range recommended by the American College of Medical Genetics and Genomics (ACMG). The survey results also showed that younger (≤ 18 years) individuals were about 3-times as successful in keeping their blood Phe concentrations within the recommended clinical range compared with adults. Blood Phe over 360 μmol/L was reported in one-quarter (25.5%) of ≤ 18 year old individuals and almost two-thirds (61.5%) of adults. A little more than half (51.7%) of respondents reported having difficulty in managing their PKU, including the maintenance of a Phe-restricted diet. Individuals with PKU desire new treatments that would allow them to increase their intake of natural protein, discontinue or reduce their intake of medical foods (medical formula and foods modified to be low in protein), improve their mental health (including a reduction in depression and anxiety), and a reduction of their blood Phe concentrations. Respondents preferred oral administration of any newly developed therapies and, in general, disliked therapeutic injections. Injections at home were preferred over injections at a clinic. Payers, government agencies, clinicians, and industry partners should consider patient input when developing and approving new therapies and treatments for PKU. PMID:27014571

  3. How Do Health Care Providers Diagnose Phenylketonuria (PKU)?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose phenylketonuria (PKU)? Skip sharing on social ... disabilities. 2 How are newborns tested for PKU? Health care providers conduct a PKU screening test using a ...

  4. Muscle-directed gene therapy for phenylketonuria (PKU): Development of transgenic mice with muscle-specific phenylalanine hydroxylase expression

    SciTech Connect

    Harding, C.O.; Messing, A.; Wolff, J.A.

    1994-09-01

    Phenylketonuria (PKU) is an attractive target for gene therapy because of shortcomings in current therapy including lifelong commitment to a difficult and expensive diet, persistent mild cognitive deficits in some children despite adequate dietary therapy, and maternal PKU syndrome. Phenylalanine hydroxylase (PAH) is normally expressed only in liver, but we propose to treat PKU by introducing the gene for PAH into muscle. In order to evaluate both the safety and efficacy of this approach, we have a developed a trangenic mouse which expresses PAH in both cardiac and skeletal muscle. The transgene includes promoter and enhancer sequences from the mouse muscle creatine kinase (MCK) gene fused to the mouse liver PAH cDNA. Mice which have inherited the transgene are healthy, active, and do not exhibit any signs of muscle weakness or wasting. Ectopic PAH expression in muscle is not detrimental to the health, neurologic function, or reproduction of the mice. Pah{sup enu2} hyperphenylalaninemic mice, a model of human PAH deficiency, bred to carry the transgene have substantial PAH expression in cardiac and skeletal muscle but none in liver. Muscle PAH expression alone does not complement the hyperphenylalaninemic phenotype of Pah{sup enu2} mice. However, administration of reduced tetrahydrobiopterin to transgenic Pah{sup enu2} mice is associated with a 25% mean decrease in serum phenylalanine levels. We predict that ectopic expression of PAH in muscle along with adequate muscle supplies of reduced biopterin cofactor will decrease hyperphenylalaninemia in PKU.

  5. Phenylketonuria (PKU). ARC Q&A #101-53.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This fact sheet uses a question-and-answer format to summarize what is known about phenylketonuria (PKU), an inherited metabolic disease that leads to mental retardation and other developmental disabilities if untreated in infancy. Questions and answers address the following topics: what PKU is; how PKU is inherited; the diagnosis of PKU; the…

  6. Pearl S. Buck and phenylketonuria (PKU).

    PubMed

    Finger, Stanley; Christ, Shawn E

    2004-03-01

    In 1921, Pearl S. Buck gave birth to a daughter, Carol, who became severely retarded and was eventually institutionalized at the Vineland Training School in New Jersey. To help pay for her daughter's care, Buck wrote The Good Earth in 1931, and then other novels and biographies about her life in China, for which she was awarded the Nobel and Pulitzer Prizes, and honored around the world. Years later, she published The Child Who Never Grew, a short piece about her daughter's retardation that also revealed her desperate search for answers and good clinical care. Asbjørn Følling distinguished phenylketonuria (PKU) from other forms of childhood retardation in the mid-1930s, and new assays and biochemical findings eventually led to ways to circumvent the devastating effects of PKU. But for Carol Buck, these advances came too late. It was not until the 1960s that physicians confirmed that her severe retardation was caused by PKU. PMID:15370336

  7. New Strategies for the Treatment of Phenylketonuria (PKU)

    PubMed Central

    Strisciuglio, Pietro; Concolino, Daniela

    2014-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the disease’s clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in the near future. PMID:25375236

  8. What Are Common Treatments for Phenylketonuria (PKU)?

    MedlinePlus

    ... better functioning and improved overall health. A PKU Formula People who follow the PKU diet will not ... from food. Therefore, they must drink a special formula. A newborn who is diagnosed with PKU should ...

  9. Parental strategies to help children with phenylketonuria (PKU) cope with feeling different.

    PubMed

    Zwiesele, Sheila; Bannick, Allison; Trepanier, Angela

    2015-08-01

    This study assessed feelings of differentness in children with phenylketonuria (PKU) and elicited parental coping strategies. A total of 22 parents of 7- to 12-year-old patients with PKU completed qualitative interviews, which assessed whether they think their children feel different from their peers and identified potential solution strategies. The results showed that most parents indicated their child feels different due to PKU, which is frequently triggered by situations surrounding food. PKU community involvement and educating others about PKU were perceived by parents as useful coping strategies. Talking to children about differences was frequently used but one of the least effective strategies. Extended family, clinicians, and teachers also attempted to help children cope with feeling different with varying degrees of success. We concluded that most parents perceive that their child with PKU feels different and have developed strategies to manage these feelings. However, a subset struggle with helping their child cope and may benefit from assistance from healthcare providers. PMID:25920535

  10. A Current Look at Phenylketonuria (PKU).

    ERIC Educational Resources Information Center

    Fischer, Margaret

    Research was reviewed on the current status of phenylketonuria, an hereditary amino acid metabolic disorder that can cause severe mental retardation, physical complications, and emotional difficulties if not detected and treated early in childhood. A majority of the research cited was published in the 1960's. Topics covered were: discovery of…

  11. Mental health and social functioning in early treated Phenylketonuria: the PKU-COBESO study.

    PubMed

    Jahja, Rianne; Huijbregts, Stephan C J; de Sonneville, Leo M J; van der Meere, Jaap J; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, M Estela; Brouwers, Martijn C G J; Hofstede, Floris C; de Vries, Maaike C; Janssen, Mirian C H; van der Ploeg, Ans T; Langendonk, Janneke G; van Spronsen, Francjan J

    2013-01-01

    This article presents a new Dutch multicenter study ("PKU-COBESO") into cognitive and behavioral sequelae of early and continuously treated Phenylketonuria (PKU) patients. Part of the study sample will consist of young adult PKU patients who have participated in a large neuropsychological study approximately 10 years ago, when they were 7-to-15-year-olds (Huijbregts et al., 2002 [1]). Their neurocognitive development will be mapped in association with their earlier and continued metabolic history, taking into account possible changes in, for instance, medication. A second part of the sample will consist of PKU patients between the ages of 7 and approximately 40 years (i.e., born in or after 1974, when neonatal screening was introduced in The Netherlands), who have not participated in the earlier neuropsychological study. Again, their cognitive functioning will be related to their metabolic history. With respect to aspects of cognition, there will be an emphasis on executive functioning. The concept of executive functioning will however be extended with further emphasis on the impact of cognitive deficits on the daily lives of PKU patients, aspects of social cognition, social functioning, and behavior/mental health (i.e., COgnition, BEhavior, SOcial functioning: COBESO). In addition to a description of the PKU-COBESO study, some preliminary results with respect to mental health and social functioning will be presented in this article. Thirty adult PKU patients (mean age 27.8, SD 6.4) and 23 PKU patients under the age of 18 years (mean age 11.0, SD 3.3) were compared to 14 (mean age 26.9 years, SD 5.9) and 7 matched controls (mean age 10.5, SD 2.6) respectively, with respect to their scores on the Adult Self-Report or Child Behavior Checklist (measuring mental health problems) and the Social Skills Checklist or Social Skills Rating System (measuring social skills). Whereas there were very few significant group differences (except for mental health problems in the

  12. Phenylketonuria

    MedlinePlus

    ... without the ability to properly break down an amino acid called phenylalanine. Causes Phenylketonuria (PKU) is inherited, which ... which is needed to break down the essential amino acid phenylalanine. Phenylalanine is found in foods that contain ...

  13. Education of Students with Phenylketonuria (PKU): Information for Teachers, Administrators and Other School Personnel.

    ERIC Educational Resources Information Center

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

    This booklet summarizes current knowledge about phenylketonuria (PKU), an inherited condition that results in severe mental retardation if untreated, and discusses the psychoeducational implications of the condition. The introduction stresses the importance of early diagnosis (during the first days of life) and the effectiveness of a diet that…

  14. Pharmacologic inhibition of L-tyrosine degradation ameliorates cerebral dopamine deficiency in murine phenylketonuria (PKU)

    PubMed Central

    Harding, Cary O.; Winn, Shelley R.; Gibson, K. Michael; Arning, Erland; Bottiglieri, Teodoro; Grompe, Markus

    2014-01-01

    Summary Monoamine neurotransmitter deficiency has been implicated in the etiology of neuropsychiatric symptoms associated with chronic hyperphenylalaninemia in phenylketonuria (PKU). Two proposed explanations for neurotransmitter deficiency in PKU include first, that chronically elevated blood L-phenylalanine (Phe) inhibits the transport of L-tyrosine (Tyr) and L-tryptophan (Trp), the substrates for dopamine and serotonin synthesis respectively, into brain. In the second hypothesis, elevated Phe competitively inhibits brain tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities, the rate limiting steps in dopamine and serotonin synthesis. Dietary supplementation with large neutral amino acids (LNAA) including Tyr and Trp has been recommended for individuals with chronically elevated blood Phe in an attempt to restore amino acid and monoamine homeostasis in brain. As a potential alternative treatment approach, we demonstrate that pharmacologic inhibition of Tyr degradation through oral administration of nitisinone (NTBC) yielded sustained increases in blood and brain Tyr, decreased blood and brain Phe, and consequently increased dopamine synthesis in a murine model of PKU. Our results suggest that Phe-mediated inhibition of TH activity is the likely mechanism of impaired dopamine synthesis in PKU. Pharmacologic inhibition of Tyr degradation may be a promising adjunct therapy for CNS monoamine neurotransmitter deficiency in hyperphenylalaninemic individuals with PKU. PMID:24487571

  15. Pharmacologic inhibition of L-tyrosine degradation ameliorates cerebral dopamine deficiency in murine phenylketonuria (PKU).

    PubMed

    Harding, Cary O; Winn, Shelley R; Gibson, K Michael; Arning, Erland; Bottiglieri, Teodoro; Grompe, Markus

    2014-09-01

    Monoamine neurotransmitter deficiency has been implicated in the etiology of neuropsychiatric symptoms associated with chronic hyperphenylalaninemia in phenylketonuria (PKU). Two proposed explanations for neurotransmitter deficiency in PKU include first, that chronically elevated blood L-phenylalanine (Phe) inhibits the transport of L-tyrosine (Tyr) and L-tryptophan (Trp), the substrates for dopamine and serotonin synthesis respectively, into brain. In the second hypothesis, elevated Phe competitively inhibits brain tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities, the rate limiting steps in dopamine and serotonin synthesis. Dietary supplementation with large neutral amino acids (LNAA) including Tyr and Trp has been recommended for individuals with chronically elevated blood Phe in an attempt to restore amino acid and monoamine homeostasis in brain. As a potential alternative treatment approach, we demonstrate that pharmacologic inhibition of Tyr degradation through oral administration of nitisinone (NTBC) yielded sustained increases in blood and brain Tyr, decreased blood and brain Phe, and consequently increased dopamine synthesis in a murine model of PKU. Our results suggest that Phe-mediated inhibition of TH activity is the likely mechanism of impaired dopamine synthesis in PKU. Pharmacologic inhibition of Tyr degradation may be a promising adjunct therapy for CNS monoamine neurotransmitter deficiency in hyperphenylalaninemic individuals with PKU. PMID:24487571

  16. Phenylketonuria (PKU)

    MedlinePlus

    ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Staff Contacts Clinical Trials Resources and Publications For Patients and Consumers For Researchers and Health ...

  17. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    PubMed

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. PMID:26653793

  18. Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an interim report of the PKU MOMS sub-registry.

    PubMed

    Grange, Dorothy K; Hillman, Richard E; Burton, Barbara K; Yano, Shoji; Vockley, Jerry; Fong, Chin-To; Hunt, Joellen; Mahoney, John J; Cohen-Pfeffer, Jessica L

    2014-05-01

    For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol/L is critical due to the toxicity of elevated Phe to the fetus. Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin (BH4) responsive patients with PKU, in conjunction with a Phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. As of June 3, 2013, the Maternal Phenylketonuria Observational Program (PKU MOMS) sub-registry contained data from 21 pregnancies - in women with PKU who were treated with sapropterin either before (N=5) or during (N=16) pregnancy. Excluding data for spontaneous abortions (N=4), the data show that the mean of median blood Phe [204.7±126.6μmol/L (n=14)] for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood Phe [267.4±300.7μmol/L (n=3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360μmol/L threshold. When median blood Phe concentration was <360μmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was >360μmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot

  19. Phenylketonuria variants in Ontario.

    PubMed Central

    1976-01-01

    Since mass screening of the newborn population for phenylketonuria (PKU) by the Guthrie test was begun in Ontario in July 1965 many variants of PKU have been recognized in the 96 to 97% screened. Seventy-one cases of classic PKU were detected (four were missed). Of 48 cases of persistent hyperphenylalaninemia discovered, 18 were classified as atypical PKU and 30 as persistent benign hyperphenylalaninemia. Numerous infants with transient hyperphenylalaninemia (initial values over 10 mg/dl in 12), in many instances the result of transient neonatal tyrosinemia, were discovered. There was a slight predominance of males. Serum phenylalanine values of up to 15 mg/dl seemed to be harmless to the developing brain. A survey of 67 247 adults in the general population revealed 1 person with PKU and 1 with persistent benign hyperphenylalaninemia; both had normal intelligence quotients. Of 1548 mothers of retarded children tested, none had hyperphenylalaninemia. PMID:953933

  20. Hepatitis virus protein X-Phenylalanine Hydroxylase fusion proteins identified in PKU mice treated with AAV-WPRE vectors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing the Pahenu2 mouse model for phenylketonuria (PKU), we developed an improved expression vector containing the Woodchuck Hepatitis Virus post-transcriptional regulatory element inserted into a rAAV-mPAH construct (rAAV-mPAH-WPRE) for treatment of PKU. Following portal vein delivery of these ...

  1. What Is Phenylketonuria (PKU)?

    MedlinePlus

    ... have it? For more information... Acknowledgments Concept 15 : DNA and proteins are key molecules of the cell nucleus. Learn the basic chemistry of DNA and proteins. Concept 27 : Mutations are changes in ...

  2. Learning about Phenylketonuria (PKU)

    MedlinePlus

    ... Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers Genomic ...

  3. Nutritional issues in treating phenylketonuria.

    PubMed

    Feillet, François; Agostoni, Carlo

    2010-12-01

    A phenylalanine (Phe)-restricted diet is the mainstay of phenylketonuria (PKU) treatment, and, in recent years, the nutritional management of PKU has become more complex in order to optimize patients' growth, development and diet compliance. Dietary restriction of Phe creates a diet similar to a vegan diet, and many of the nutritional concerns and questions applicable to vegans who wish to avoid animal products are also relevant to patients with PKU. Owing to their nutritional characteristics, breast milk and breastfeeding should be given greater consideration as a useful food in patients with PKU and in those with other inborn errors of metabolism. Further key issues for consideration include the quality of the available amino acid substitutes, the neurotrophic and neuroprotective effects of added long-chain polyunsaturated fatty acids (e.g. docosahexaenoic acid), micronutrient deficiencies, bone disease and antioxidant status. Long-term dietary guidance and monitoring of the nutritional status of patients with PKU should be part of a follow-up programme that continues for life. PMID:20151202

  4. Psychiatric symptoms and disorders in phenylketonuria.

    PubMed

    Brumm, V L; Bilder, D; Waisbren, S E

    2010-01-01

    Psychological and psychiatric problems are well documented across the lifespan of individuals with early-treated phenylketonuria (PKU). Early-treated children and adolescents tend to display attentional problems, school problems, lower achievement motivation, decreased social competence, decreased autonomy, and low-self-esteem. As they enter adulthood, early-treated individuals may carry forward low self-esteem and lack of autonomy but also tend to develop depressed mood, generalized anxiety, phobias, decreased positive emotions, social maturity deficits, and social isolation. The correlation between level of metabolic control and severity of symptoms suggests a biological basis of psychiatric dysfunction. Additionally, psychosocial factors such as the burden of living with a chronic illness may contribute to psychological and psychiatric outcomes in PKU. The lack of a PKU-specific psychiatric phenotype combined with the observation that not everyone with PKU is affected highlights the complexity of the problem. More research on psychiatric and psychological outcomes in PKU is required. Of particular importance is the routine monitoring of emotional, behavioral, and psychosocial symptoms in individuals with this metabolic disorder. Longitudinal studies are required to evaluate the impact of new and emerging therapies on psychiatric and psychosocial functioning in PKU. Unidentified or untreated emotional and behavioral symptoms may have a significant, lifelong impact on the quality of life and social status of patients. PMID:20123472

  5. Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

    PubMed Central

    Schuck, Patrícia Fernanda; Malgarin, Fernanda; Cararo, José Henrique; Cardoso, Fabiola; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition. PMID:26425393

  6. Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.

    PubMed

    Schuck, Patrícia Fernanda; Malgarin, Fernanda; Cararo, José Henrique; Cardoso, Fabiola; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-09-01

    Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition. PMID:26425393

  7. Progress toward cell-directed therapy for phenylketonuria.

    PubMed

    Harding, Co

    2008-08-01

    Phenylketonuria (PKU) is one of the most common inborn errors of metabolism with an annual incidence of approximately 1:16,000 live births in North America. Contemporary therapy relies upon lifelong dietary protein restriction and supplementation with phenylalanine-free medical foods. This therapy is expensive and unpalatable; dietary compliance is difficult to maintain throughout life. Non-adherence to the diet is associated with learning disabilities, adult-onset neurodegenerative disease, and maternal PKU syndrome. The fervent dream of many individuals with PKU is a more permanent cure for this disease. This paper will review ongoing efforts to develop viable cell-directed therapies, in particular cell transplantation and gene therapy, for the treatment of PKU. PMID:18498375

  8. Relationship between age and white matter integrity in children with phenylketonuria.

    PubMed

    Wesonga, Erika; Shimony, Joshua S; Rutlin, Jerrel; Grange, Dorothy K; White, Desiree A

    2016-06-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU. PMID:27114916

  9. Relationship between age and white matter integrity in children with phenylketonuria

    PubMed Central

    Wesonga, Erika; Shimony, Joshua S.; Rutlin, Jerrel; Grange, Dorothy K.; White, Desiree A.

    2016-01-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU. PMID:27114916

  10. Management of Newborn Infants with Phenylketonuria.

    ERIC Educational Resources Information Center

    Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

    The booklet covers the identification, diagnosis, and clinical treatment of newborns with Phenylketonuria (PKU), an inborn error of metabolism, which, if untreated, can lead to mental retardation. An initial section considers biochemical and genetic factors of PKU including a diagram of aromatic amino acid hydroxylation systems. Screening…

  11. ACOG Committee Opinion No. 449: Maternal phenylketonuria.

    PubMed

    2009-12-01

    Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine, and elevated levels of Phe and Phe metabolite. All women with PKU or hyperphenylalaninemia should be strongly encouraged to receive family planning and preconception counseling. Women with PKU or hyperphenylalaninemia should begin appropriate, medically directed dietary phenylalanine restriction before conception. PMID:20134300

  12. Developing and testing a programmed instruction unit on PKU.

    PubMed

    Marino, M A

    1980-01-01

    The methods used in developing and evaluating a programmed instruction unit on PKU and its dietary management are presented. The unit was shown to be a reliable, valid, effective, and enjoyable teaching aid for parents. All ten mothers using the text showed improvement in their post-test scores, and analysis by correlated sample student t-test demonstrated that the increases were highly significant (p of less than 0.0005). In addition, the mothers' responses to the learning experience were notably favorable. All enjoyed the text and strongly recommended its use for new families in the Clinic. The results indicate that programmed instruction may also be useful in other areas of patient nutrition education. Although not substitutes for the one-to-one counseling provided by nutritionists, such tools offer effective, self-paced, and individualized instruction which can be utilized by patients in their own homes. PMID:7391442

  13. PKU (Phenylketonuria) in Your Baby

    MedlinePlus

    ... which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in your body. Without treatment, ... which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in ...

  14. PHENYLKETONURIA, A COMPREHENSIVE BIBLIOGRAPHY, 1964.

    ERIC Educational Resources Information Center

    Children's Bureau (DHEW), Washington, DC.

    INTENDED AS AN AID TO PROFESSIONAL AND TECHNICAL PERSONS INTERESTED IN PHENYLKETONURIA (PKU), THE BIBLIOGRAPHY LISTS AND ANNOTATES 817 ITEMS. CONTENT DIVISIONS ARE (1) GENERAL--MONOGRAPHS AND ARTICLES, (2) BIOCHEMISTRY--METABOLISM, EXPERIMENTS, TESTS, AND CASES IN WHICH THE EMPHASIS IS ON BIOCHEMISTRY, (3) GENETICS--GENE STUDIES, HEREDITARY…

  15. Micronutrient status in phenylketonuria.

    PubMed

    Robert, M; Rocha, J C; van Rijn, M; Ahring, K; Bélanger-Quintana, A; MacDonald, A; Dokoupil, K; Gokmen Ozel, H; Lammardo, A M; Goyens, P; Feillet, F

    2013-01-01

    Patients with phenylketonuria (PKU) encompass an 'at risk' group for micronutrient imbalances. Optimal nutrient status is challenging particularly when a substantial proportion of nutrient intake is from non-natural sources. In PKU patients following dietary treatment, supplementation with micronutrients is a necessity and vitamins and minerals should either be added to supplement phenylalanine-free l-amino acids or given separately. In this literature review of papers published since 1990, the prevalence of vitamin and mineral deficiency is described, with reference to age of treatment commencement, type of treatment, dietary compliance, and dietary practices. Biological micronutrient inadequacies have been mainly reported for zinc, selenium, iron, vitamin B12 and folate. The aetiology of these results and possible clinical and biological implications are discussed. In PKU there is not a simple relationship between the dietary intake and nutritional status, and there are many independent and interrelated complex factors that should be considered other than quantitative nutritional intake. PMID:24113686

  16. Breastfeeding Infants with Phenylketonuria in the United States and Canada

    PubMed Central

    Press, Nancy; Knafl, Kathleen A.; Steiner, Robert D.; Houck, Gail M.

    2014-01-01

    Abstract Objective: This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Subjects and Methods: Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Results: Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ2=30.33, p<0.001; n=72 vs. n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one modal duration category (n=20, 22%) at less than 1 month. The timing of the addition of commercial infant formula to supplement breastfeeding or expressed mothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ2 (42, n=73)=88.13, p<0.001. Conclusions: PKU is treated with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is challenging in part because Phe intake is difficult to determine precisely. We studied breastfeeding duration in infants with PKU and factors associated with success. Further research should identify the unique needs of mothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU. PMID:24350704

  17. Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

    NASA Astrophysics Data System (ADS)

    Javanmard, M.; Davis, R. W.

    2014-02-01

    Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

  18. Newborn screening of phenylketonuria using direct analysis in real time (DART) mass spectrometry.

    PubMed

    Wang, Chunyan; Zhu, Hongbin; Cai, Zongwei; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-04-01

    Phenylketonuria (PKU) is commonly included in the newborn screening panel of most countries, with various techniques being used for quantification of L-phenylalanine (Phe). To diagnose PKU as early as possible in newborn screening, a rapid and simple method of analysis was developed. Using direct analysis in real time (DART) ionization coupled with triple-quadrupole tandem mass spectrometry (TQ-MS/MS) and with use of a 12 DIP-it tip scanner autosampler in positive ion mode, we analyzed dried blood spot (DBS) samples from PKU newborns. The concentration of Phe was determined using multiple reaction monitoring mode with the nondeuterated internal standard N,N-dimethylphenylalanine. The results of the analysis of DBS samples from newborns indicated that the DART-TQ-MS/MS method is fast, accurate, and reproducible. The results prove that this assay as a newborn screen for PKU can be performed in 18 s per sample for the quantification of Phe in DBS samples. DART-TQ-MS/MS analysis of the Phe concentration in DBS samples allowed us to screen newborns for PKU. This innovative protocol is rapid and can be effectively applied on a routine basis to analyze a large number of samples in PKU newborn screening and PKU patient monitoring. PMID:23397086

  19. Caring for children with phenylketonuria

    PubMed Central

    Casey, Linda

    2013-01-01

    Abstract Objective To provide an overview of the diagnosis and management of phenylketonuria (PKU) in childhood with an emphasis on aspects relevant to family physicians providing ongoing care. Sources of information The author’s experience as the clinic physician in a regional pediatric PKU clinic is supplemented with references providing evidence for key points. Main message While metabolic clinics typically provide guidance regarding the specific management of PKU, the family doctor has an essential role in providing ongoing medical care. Conclusion Children and families have much to gain from strong relationships with family doctors, and family doctors can confidently provide care with awareness of the very few potential special needs of patients with PKU. PMID:23946023

  20. Late-Treated Phenylketonuria and Partial Reversibility of Intellectual Impairment

    ERIC Educational Resources Information Center

    Grosse, Scott D.

    2010-01-01

    Individuals with late-treated phenylketonuria (PKU) not detected by newborn screening but who followed dietary treatment for at least 12 months before 7 years of age have intelligence quotient (IQ) scores that range from severe impairment to the low-normal range. Among adults with late-treated PKU in California, 85% of those who were born from…

  1. Phenylketonuria in adulthood: a collaborative study.

    PubMed

    Koch, R; Burton, B; Hoganson, G; Peterson, R; Rhead, W; Rouse, B; Scott, R; Wolff, J; Stern, A M; Guttler, F; Nelson, M; de la Cruz, F; Coldwell, J; Erbe, R; Geraghty, M T; Shear, C; Thomas, J; Azen, C

    2002-09-01

    During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural

  2. Future treatment strategies in phenylketonuria.

    PubMed

    van Spronsen, Francjan J; Enns, Gregory M

    2010-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy. During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU. PMID:20123478

  3. Maternal Phenylketonuria (MPKU)

    PubMed Central

    Schoonheyt, W.E.; Hanley, W.B.; Clarke, J.T.R.; Austin, V.; Howe, D.A.

    1986-01-01

    Untreated maternal phenylketonuria (MPKU) is a major cause of microcephaly, congenital heart disease, intrauterine growth retardation and mental retardation in the offspring of mothers who have the disease. There is evidence, however, that dietary restriction of phenylalanine in the mother before conception and throughout the pregnancy will reduce the risk of these congenital anomalies in the fetus. It is important to be alert to this preventable cause of developmental retardation and congenital abnormalities in all pregnancies until the stage is reached where every woman of child-bearing age has been through the neonatal PKU-screening program. Family physicians are advised to consider prenatal or premarital screening for PKU of all female patients of child-bearing age for the next generation. PMID:21267327

  4. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations. PMID:803884

  5. A GC/MS-based metabolomic approach for reliable diagnosis of phenylketonuria.

    PubMed

    Xiong, Xiyue; Sheng, Xiaoqi; Liu, Dan; Zeng, Ting; Peng, Ying; Wang, Yichao

    2015-11-01

    Although the phenylalanine/tyrosine ratio in blood has been the gold standard for diagnosis of phenylketonuria (PKU), the disadvantages of invasive sample collection and false positive error limited the application of this discriminator in the diagnosis of PKU to some extent. The aim of this study was to develop a new standard with high sensitivity and specificity in a less invasive manner for diagnosing PKU. In this study, an improved oximation-silylation method together with GC/MS was utilized to obtain the urinary metabolomic information in 47 PKU patients compared with 47 non-PKU controls. Compared with conventional oximation-silylation methods, the present approach possesses the advantages of shorter reaction time and higher reaction efficiency at a considerably lower temperature, which is beneficial to the derivatization of some thermally unstable compounds, such as phenylpyruvic acid. Ninety-seven peaks in the chromatograms were identified as endogenous metabolites by the National Institute of Standards and Technology (NIST) mass spectra library, including amino acids, organic acids, carbohydrates, amides, and fatty acids. After normalization of data using creatinine as internal standard, 19 differentially expressed compounds with p values of <0.05 were selected by independent-sample t test for the separation of the PKU group and the control group. A principal component analysis (PCA) model constructed by these differentially expressed compounds showed that the PKU group can be discriminated from the control group. Receiver-operating characteristic (ROC) analysis with area under the curve (AUC), specificity, and sensitivity of each PKU marker obtained from these differentially expressed compounds was used to evaluate the possibility of using these markers for diagnosing PKU. The largest value of AUC (0.987) with high specificity (0.936) and sensitivity (1.000) was obtained by the ROC curve of phenylacetic acid at its cutoff value (17.244 mmol/mol creatinine

  6. Intellectual, neurologic, and neuropsychologic outcome in untreated subjects with nonphenylketonuria hyperphenylalaninemia. German Collaborative Study on Phenylketonuria.

    PubMed

    Weglage, J; Ullrich, K; Pietsch, M; Fünders, B; Güttler, F; Harms, E

    1997-09-01

    Based on the serum phenylalanine levels under free diet patients with hyperphenylalaninemia are classified as "classical" (>1200 micromol/L), "mild" (600-1200 micromol/L), or "non-phenylketonuria (PKU)-hyperphenylalaninemia" (<600 micromol/L). Recent studies revealed intellectual, neurologic, and neuropsychologic deficits as well as abnormalities of cerebral white matter (magnetic resonance imaging, MRI) in patients with early and adequately treated PKU. In addition deficits in IQ were reported for a group of 4-y-old patients with untreated mild PKU and non-PKU hyperphenylalaninemia (serum phenylalanine levels below 900 micromol/L). As a consequence, a lifelong diet with serum phenylalanine levels below 400 micromol/L was recommended even for those patients with serum phenylalanine levels remaining consistently between 400 and 600 micromol/L. Generally patients with non-PKU hyperphenylalaninemia were not treated, as a normal outcome was suspected, but the clinical development of patients with non-PKU hyperphenylalaninemia was not so far studied systematically. We assessed 28 untreated patients with non-PKU hyperphenylalaninemia (age: mean = 21.8, SD = 4.2 y) for IQ, school and job career, clinical-neurologic development, fine motor performances, selective and sustained attention, as well as for frontal lobe-dependent "executive functions." In addition, cranial MRI was obtained in 10 of these patients. Compared with healthy control subjects, matched for age, sex, and socioeconomic status, the patients reached normal results in all clinical and psychometric tests. Cranial MRI revealed no abnormalities. Additionally, no significant correlations between serum phenylalanine levels and test results were obtained. In the absence of any demonstrative effect, treatment is unlikely to be of significant effect in patients with non-PKU hyperphenylalaninemia. PMID:9284280

  7. Intelligence and Phenylketonuria: Effects of Diet Termination.

    ERIC Educational Resources Information Center

    Koff, Elissa; And Others

    1979-01-01

    Trends in intellectual functioning before and after diet termination were examined in 30 children (5-11 years old) with PKU (Phenylketonuria, a metabolic disorder) treated before 6 weeks of age and on a liberal diet for a mean of 3 years since the mean age of 59 months. Journal availability: C.V. Mosby Company, 11830 Westline Industrial Drive, St.…

  8. Altered DNA methylation in PAH deficient phenylketonuria.

    PubMed

    Dobrowolski, Steven F; Lyons-Weiler, James; Spridik, Kayla; Biery, Amy; Breck, Jane; Vockley, Jerry; Yatsenko, Svetlana; Sultana, Tamanna

    2015-01-01

    While phenylalanine (PHE) is the toxic insult in phenylketonuria (PKU), mechanisms underlying PHE toxicity remain ill-defined. Altered DNA methylation in response to toxic exposures is well-recognized. DNA methylation patterns were assessed in blood and brain from PKU patients to determine if PHE toxicity impacts methylation. Methylome assessment, utilizing methylated DNA immunoprecipitation and paired-end sequencing, was performed in DNA obtained from brain tissue of classical PKU patients, leukocytes from poorly controlled PKU patients, leukocytes from well controlled PKU patients, and appropriate control tissues. In PKU brain tissue, expression analysis determined the impact of methylation on gene function. Differential methylation was observed in brain tissue of PKU patients and expression studies identified downstream impact on gene expression. Altered patterns of methylation were observed in leukocytes of well controlled and poorly controlled patients with more extensive methylation in patients with high PHE exposure. Differential methylation of noncoding RNA genes was extensive in patients with high PHE exposure but minimal in well controlled patients. Methylome repatterning leading to altered gene expression was present in brain tissue of PKU patients, suggesting a role in neuropathology. Aberrant methylation is observed in leukocytes of PKU patients and is influenced by PHE exposure. DNA methylation may provide a biomarker relating to historic PHE exposure. PMID:25990862

  9. Current situation and prospects of newborn screening and treatment for Phenylketonuria in China — compared with the current situation in the United States, UK and Japan

    PubMed Central

    Mei, Lin; Song, Peipei; Kokudo, Norihiro; Xu, Lingzhong; Tang, Wei

    2013-01-01

    Summary Phenylketonuria (PKU) is a treat-able and prevent-able inborn error of metabolism which leads to severe mental retardation and neurobehavioral abnormalities. A screening program, especially for early detection, combined with a Phe-restricted therapeutic diet can help to control the process of PKU of most patients. The China government has put more emphasis on newborn screening and treatment against PKU, yet by comparing the situation of newborn screening and treatment against PKU in China and the relatively developed countries — United States, United Kingdom and Japan, the newborn screening and treatment against PKU in China is relatively weak and many deficiencies are found. More studies concerning multi-stage target blood Phe concentration criteria, a policy that requires newborn screening has to be taken, better financial support for newborn screening, publicity for newborn screening, and national guidelines for treatment of PKU may be prospects in China and may provide some support for better development of newborn screening and treatment against PKU in China. PMID:25343113

  10. Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria.

    PubMed

    Sarkissian, Christineh N; Gámez, Alejandra; Wang, Lin; Charbonneau, Marilyse; Fitzpatrick, Paul; Lemontt, Jeffrey F; Zhao, Bin; Vellard, Michael; Bell, Sean M; Henschell, Carroll; Lambert, Amy; Tsuruda, Laurie; Stevens, Raymond C; Scriver, Charles R

    2008-12-30

    Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine hydroxylase activity results in neurotoxic levels of phenylalanine. We used the Pah(enu2/enu2) PKU mouse model in short- and long-term studies of enzyme substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL conjugates) from 4 different species. The most therapeutically effective PAL (Av, Anabaena variabilis) species was one without the highest specific activity, but with the highest stability; indicating the importance of protein stability in the development of effective protein therapeutics. A PEG-Av-p.C503S/p.C565S-PAL effectively lowered phenylalanine levels in both vascular space and brain tissue over a >90 day trial period, resulting in reduced manifestations associated with PKU, including reversal of PKU-associated hypopigmentation and enhanced animal health. Phenylalanine reduction occurred in a dose- and loading-dependent manner, and PEGylation reduced the neutralizing immune response to the enzyme. Human clinical trials with PEG-Av-p.C503S/p.C565S-PAL as a treatment for PKU are underway. PMID:19095795

  11. PKU and the Schools: Information for Teachers, Administrators and Other School Personnel.

    ERIC Educational Resources Information Center

    Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

    Designed to acquaint teachers, administrators and other school personnel with phenylketonuria (PKU - an inborn error of metabolism which requires dietary intervention), the booklet reviews school problems related to the condition. Introductory information concerns the nature, treatment, and screening and diagnosis of PKU. Diet management is…

  12. Phenylketonuria Scientific Review Conference: state of the science and future research needs.

    PubMed

    Camp, Kathryn M; Parisi, Melissa A; Acosta, Phyllis B; Berry, Gerard T; Bilder, Deborah A; Blau, Nenad; Bodamer, Olaf A; Brosco, Jeffrey P; Brown, Christine S; Burlina, Alberto B; Burton, Barbara K; Chang, Christine S; Coates, Paul M; Cunningham, Amy C; Dobrowolski, Steven F; Ferguson, John H; Franklin, Thomas D; Frazier, Dianne M; Grange, Dorothy K; Greene, Carol L; Groft, Stephen C; Harding, Cary O; Howell, R Rodney; Huntington, Kathleen L; Hyatt-Knorr, Henrietta D; Jevaji, Indira P; Levy, Harvey L; Lichter-Konecki, Uta; Lindegren, Mary Lou; Lloyd-Puryear, Michele A; Matalon, Kimberlee; MacDonald, Anita; McPheeters, Melissa L; Mitchell, John J; Mofidi, Shideh; Moseley, Kathryn D; Mueller, Christine M; Mulberg, Andrew E; Nerurkar, Lata S; Ogata, Beth N; Pariser, Anne R; Prasad, Suyash; Pridjian, Gabriella; Rasmussen, Sonja A; Reddy, Uma M; Rohr, Frances J; Singh, Rani H; Sirrs, Sandra M; Stremer, Stephanie E; Tagle, Danilo A; Thompson, Susan M; Urv, Tiina K; Utz, Jeanine R; van Spronsen, Francjan; Vockley, Jerry; Waisbren, Susan E; Weglicki, Linda S; White, Desirée A; Whitley, Chester B; Wilfond, Benjamin S; Yannicelli, Steven; Young, Justin M

    2014-06-01

    New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use

  13. Classroom Demonstration of a Spot Test for Pbenylpyruvic Acid and Its Relationship to Phenylketonuria

    ERIC Educational Resources Information Center

    Halkides, Christopher J.

    2004-01-01

    Classical phenylketonuria (PKU) is caused by a lack activity in the enzyme phenylalanine hydroxylase, leading to elevated concentrations of phenylalanine in the blood. A simple demonstration and three advanced demonstrations of a spot test for phenylpyruvic acid and its relationship to phenylketonuria are given.

  14. Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: A DTI study of the corpus callosum☆

    PubMed Central

    White, Desiree A.; Connor, Lisa Tabor; Nardos, Binyam; Shimony, Joshua S.; Archer, Rebecca; Snyder, Abraham Z.; Moinuddin, Asif; Grange, Dorothy K.; Steiner, Robert D.; McKinstry, Robert C.

    2013-01-01

    Structural, volumetric, and microstructural abnormalities have been reported in the white matter of the brain in individuals with phenylketonuria (PKU). Very little research, however, has been conducted to investigate the development of white matter in children with PKU, and the developmental trajectory of their white matter microstructure is unknown. In the current study, diffusion tensor imaging (DTI) was used to examine the development of the microstructural integrity of white matter across six regions of the corpus callosum in 34 children (7–18 years of age) with early- and continuously-treated PKU. Comparison was made with 61 demographically-matched healthy control children. Two DTI variables were examined: mean diffusivity (MD) and relative anisotropy (RA). RA was comparable to that of controls across all six regions of the corpus callosum. In contrast, MD was restricted for children with PKU in anterior (i.e., genu, rostral body, anterior midbody) but not posterior (posterior midbody, isthmus, splenium) regions of the corpus callosum. In addition, MD restriction became more pronounced with increasing age in children with PKU in the two most anterior regions of the corpus callosum (i.e., genu, rostral body). These findings point to an age-related decrement in the microstructural integrity of the anterior white matter of the corpus callosum in children with PKU. PMID:20123469

  15. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    PubMed

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging. PMID:26962957

  16. [Lists of food exchanges for use in phenylketonuria and maple-syrup urine disease].

    PubMed

    Jiménez Soto, Z

    1993-09-01

    Phenylketonuria (PKU) and maple syrup urine disease (MSUD) are disorders of the amino acid metabolism. Treatment of PKU and MSUD, is based on the restriction of the involved amino acids. Diet must begin very early in life in order to prevent neurological sequelae. A wrong dietary produce central nervous system damage. The first clinical manifestations are unexplained failure to thrive, vomiting, feeding difficulties, lethargy, coma, acidosis and irritability. The most severe consequence is impaired mental development. The standard exchange foods list (EFL) used in outpatient clinics, is designed for developed countries, and contains foods that are not available in our countries. Therefore, we provide in this article a EFL, based on food that are frequently used in Central America, with data of existing food composition tables. This list is currently being used by the Costa Rica national Children's Hospital Metabolic Disease Unit. PMID:8779622

  17. What Are Common Symptoms of Phenylketonuria (PKU)?

    MedlinePlus

    ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Staff Contacts Clinical Trials Resources and Publications For Patients and Consumers For Researchers and Health ...

  18. A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.

    PubMed

    Sarkissian, C N; Shao, Z; Blain, F; Peevers, R; Su, H; Heft, R; Chang, T M; Scriver, C R

    1999-03-01

    Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC 4.3.1.5) to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC 1.14.16.1), which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease. PMID:10051643

  19. Phenylketonuria. Experience at one center in the first year of screening in California.

    PubMed

    Peterson, R M; Koch, R; Schaeffler, G E; Wohlers, A; Acosta, P B; Boyle, D

    1968-05-01

    One year's experience with phenylketonuria during the calendar year 1966, the first year for compulsory newborn screening in California, was reviewed. The over-all prevalence rate from reported cases in California during this period was one case per 19,500 persons tested. Fifty-seven persons suspected of having pku were evaluated, and 25 of them were determined to be phenylketonuric. Eleven of the 25 were infants in whom the abnormality was detected through the newborn screening program or because it was detected in a sibling through a screening program. All the newborn phenylketonuric patients were developing normally at the time of last report (although the follow-up periods were short). In nine of the other children, pku was detected because they were retarded. Five retarded children who were diagnosed as phenylketonuric at another clinic were given dietary assistance. Five additional infants had elevated serum phenylalanines but did not have the classic biochemical findings of pku and are being evaluated further. Nine infants with positive screening tests exhibited biochemical and clinical findings consistent with transient tyrosinemia. Eighteen other children were evaluated and found to have no metabolic abnormality. The newborn screening program for pku is of decided benefit in early identification of a group of infants who have a high rate of potentially serious metabolic disease. Early identification permits treatment soon enough to prevent mental retardation. Newly identified patients should be evaluated in a medical setting capable of careful pediatric, biochemical and nutritional surveillance. PMID:5652755

  20. Sapropterin Hydrochloride: Enzyme Enhancement Therapy for Phenylketonuria

    PubMed Central

    Lachmann, Robin

    2011-01-01

    Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism caused by deficiency of the enzyme phenylalanine hydroxylase (PAH). Historically PKU was a common genetic cause of severe learning difficulties and developmental delay, but with the introduction of newborn screening and early dietary management, it has become a treatable disease and people born with PKU should now have IQs and achievements similar to their peers. Dietary treatment, however, involves lifestyle changes that pervade most aspects of daily life for an individual and their family. A simple pharmacological treatment for PKU would have a great appeal. Sapropterin hydrochloride is a synthetic form of tetrahydrobiopterin, the cofactor for PAH. A proportion of mutant PAH enzymes show enhanced activity in the presence of pharmacological doses of sapropterin and, for some patients with milder forms of PKU, sapropterin can effectively lower plasma phenylalanine levels. This article discusses the potential place for sapropterin in the management of PKU and how this expensive orphan drug is being integrated into patient care in different healthcare systems. PMID:23148178

  1. Congenital and Neurological Abnormalities in Infants with Phenylketonuria

    ERIC Educational Resources Information Center

    Johnson, Charles F.; And Others

    1978-01-01

    Examined was the occurrence of congenital and neurological abnormalities in 150 children with phenylketonuria (PKU--a metabolic disorder which may result in mental retardation) age 1 year or older, who have been treated with a restricted phenylalanine diet, according to the protocol used in a nation-wide longitudinal collaborative study.…

  2. Management of phenylketonuria in Europe: survey results from 19 countries.

    PubMed

    Blau, Nenad; Bélanger-Quintana, Amaya; Demirkol, Mübeccel; Feillet, François; Giovannini, Marcello; MacDonald, Anita; Trefz, Friedrich K; van Spronsen, Francjan

    2010-02-01

    To gain better insight in the most current diagnosis and treatment practices for phenylketonuria (PKU) from a broad group of experts, a European PKU survey was performed. The questionnaire, consisting of 33 questions, was sent to 243 PKU professionals in 165 PKU centers in 23 European countries. The responses were compiled and descriptive analyses were performed. One hundred and one questionnaires were returned by 93/165 centers (56%) from 19/23 European countries (83%). The majority of respondents (77%) managed patients of all age groups and more than 90% of PKU teams included physicians or dieticians/nutritionists. The greatest variability existed especially in the definition of PKU phenotypes, therapeutic blood phenylalanine (Phe) target concentrations, and follow-up practices for PKU patients. The tetrahydrobiopterin (BH4; sapropterin) loading test was performed by 54% of respondents, of which 61% applied a single dose test (20mg/kg over 24h). BH4 was reported as a treatment option by 34%. This survey documents differences in diagnostic and treatment practices for PKU patients in European centers. In particular, recommendations for the treatment decision varied greatly between different European countries. There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline. PMID:19800826

  3. The Long-Term Use of a Low-Phenylalanine Diet in Late-Treated Phenylketonuria: A Single Case Report

    ERIC Educational Resources Information Center

    Hewitt, Philippa; Cottle, Mandy; Coleman, Carol

    2006-01-01

    Background: When phenylketonuria (PKU) is not diagnosed and long-term treatment commenced within the first few weeks of life, permanent brain damage will occur. There is some evidence to show that late diagnosed or untreated people with PKU who have severe challenging behaviours may benefit from a low phenylalanine diet [Harper & Reid (1987)…

  4. Phenylketonuria: translating research into novel therapies

    PubMed Central

    Ho, Gladys

    2014-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. It is an autosomal recessive disorder with a rate of incidence of 1 in 10,000 in Caucasian populations. Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH. Newborn screening for PKU allows early intervention, avoiding irreparable neurological damage and intellectual disability that would arise from untreated PKU. The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. This treatment is not universally available, and is only effective for a proportion (estimated 30%) of PKU patients. Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents. It is hoped that continuing efforts into these studies will translate into a significant improvement in the physical outcome, as well as quality of life, for patients with PKU. PMID:26835324

  5. Genetics of Phenylketonuria: Then and Now.

    PubMed

    Blau, Nenad

    2016-06-01

    More than 950 phenylalanine hydroxylase (PAH) gene variants have been identified in people with phenylketonuria (PKU). These vary in their consequences for the residual level of PAH activity, from having little or no effect to abolishing PAH activity completely. Advances in genotyping technology and the availability of locus-specific and genotype databases have greatly expanded our understanding of the correlations between individual gene variant, residual PAH activity, tetrahydrobiopterin (BH4 ) responsiveness, and the clinical PKU phenotype. Most patients (∼76%) have compound heterozygous PAH gene variants and one mutated allele may markedly influence the activity of the second mutated allele, which in turn may influence either positively or negatively the activity of the biologically active heterotetrameric form of the PAH. While it is possible to predict the level of BH4 responsiveness (∼71%) and PKU severity (∼78%) from the nature of the underlying gene variants, these relationships remain complex and incompletely understood. A greater understanding of these relationships may increase the potential for individualized management of PKU in future. Inherited deficiencies in BH4 metabolism account for about 1%-2% of all hyperphenylalaninemias and are clinically more severe than PKU. Almost 90% of all patients are deficient in 6-pyruvoyl-tetrahydropterin synthase and dihydropteridine reductase. PMID:26919687

  6. Nutritional status of patients with phenylketonuria in Japan.

    PubMed

    Okano, Yoshiyuki; Hattori, Toshikazu; Fujimoto, Hiroki; Noi, Kaori; Okamoto, Miki; Watanabe, Toshiaki; Watanabe, Ryoko; Fujii, Rika; Tamaoki, Tomoko

    2016-09-01

    Accumulating evidence suggests that hyperphenylalaninemia in phenylketonuria (PKU) can cause neuropsychological and psychosocial problems in diet-off adult patients, and that such symptoms improve after resumption of phenylalanine-restricted diet, indicating the need for lifetime low-phenylalanine diet. While limiting protein intake, dietary therapy should provide adequate daily intake of energy, carbohydrates, fat, vitamins, and microelements. We evaluated nutrient balance in 14 patients with classical PKU aged 4-38 years. Approximately 80-85% of the recommended dietary allowance (RDA) of protein in Japanese was supplied through phenylalanine-free (Phe-free) milk and Phe-free amino acid substitutes. Nutritional evaluation showed that the calorie and protein intakes were equivalent to the RDA. Phenylalanine intake was 9.8 ± 2.2 mg/kg of body weight/day, which maintained normal blood phenylalanine concentration by the 80% Phe-free protein rule. The protein, fat, and carbohydrate ratio was 9.5:23.9:66.6% with relative carbohydrate excess. Phe-free milk and amino acid substitutes provided 33.7% of carbohydrate, 82.1% of protein, and 66.7% of fat intake in all. Selenium and biotin intakes were 25.0% and 18.1% of the RDA and adequate intake (AI) for Japanese, respectively; both were not included in Phe-free milk. PKU patients showed low serum selenium, low urinary biotin, and high urinary 3-hydroxyisovaleric acid in this study. The intakes of magnesium, zinc, and iodine were low (71.5%, 79.5%, and 71.0% of the RDA, respectively) and that of phosphorus was 79.7% of the AI, although they were supplemented in Phe-free milk. PKU patients depend on Phe-free milk and substitutes for daily requirement of microelements and vitamins as well as protein and fat. Development of low-protein food makes it possible to achieve the aimed phenylalanine blood level, but this lowers the intake of microelements and vitamins from natural foods. The dietary habits vary continuously with

  7. Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

    ERIC Educational Resources Information Center

    Guest, J. F.; Bai, J. J.; Taylor, R. R.; Sladkevicius, E.; Lee, P. J.; Lachmann, R. H.

    2013-01-01

    Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the…

  8. Advances in the nutritional and pharmacological management of phenylketonuria

    PubMed Central

    Ney, Denise M.; Blank, Robert D.; Hansen, Karen E.

    2014-01-01

    Structural Abstract Purpose of review The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). Recent findings Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phe intact protein that represents a new dietary alternative to synthetic amino acids (AAs) for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an AA diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin (BH4), acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral AAs (LNAA) inhibit phe transport across the intestinal mucosa and blood brain barrier; LNAA are most effective for individuals unable to comply with the low-phe diet. Summary Although a low-phe synthetic AA diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to AA formula that may improve bone health, and BH4 permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management. PMID:24136088

  9. Executive function in adolescents with PKU and their siblings: Associations with biochemistry.

    PubMed

    Sharman, R; Sullivan, K; Young, R; McGill, J

    2015-09-01

    Previous research shows consistent and marked executive function impairment in children with early and continuously treated phenylketonuria. This between groups analysis (phenylketonuria group vs sibling controls) found no significant differences in executive function (although adolescents with phenylketonuria performed slightly worse than their siblings). Biochemical relationships with executive function were confined to long-term measures of high phenylalanine:tyrosine ratio exposure, as well as tyrosine exposure independent of phenylalanine. This study suggests that early and continuously treated PKU results in non-significant EF differences (compared to siblings), although the influence of long-term exposure to poorer metabolic control is still evident. PMID:26937416

  10. Executive function in adolescents with PKU and their siblings: Associations with biochemistry

    PubMed Central

    Sharman, R.; Sullivan, K.; Young, R.; McGill, J.

    2015-01-01

    Previous research shows consistent and marked executive function impairment in children with early and continuously treated phenylketonuria. This between groups analysis (phenylketonuria group vs sibling controls) found no significant differences in executive function (although adolescents with phenylketonuria performed slightly worse than their siblings). Biochemical relationships with executive function were confined to long-term measures of high phenylalanine:tyrosine ratio exposure, as well as tyrosine exposure independent of phenylalanine. This study suggests that early and continuously treated PKU results in non-significant EF differences (compared to siblings), although the influence of long-term exposure to poorer metabolic control is still evident. PMID:26937416

  11. National PKU News

    MedlinePlus

    ... and History Staff & Board How Much Phe Guthrie-Koch Scholarship Books Resources Support Us Contact Us Donors ... new Amino Acid Analysis Results This Year’s Guthrie-Koch PKU Scholarship Winners © 2016 National PKU News

  12. The molecular basis of phenylketonuria in Lithuania.

    PubMed

    Kasnauskiene, J; Giannattasio, S; Lattanzio, P; Cimbalistiene, L; Kucinskas, V

    2003-04-01

    We report the spectrum of phenylalanine hydroxylase (PAH) gene mutations in patients with phenylketonuria (PKU) residing in Lithuania. A total of 184 independent chromosomes was investigated. R408W mutation was first analysed through restriction enzyme digestion of exon 12. The remaining uncharacterised PKU chromosomes were analysed by scanning the whole coding sequence of PAH gene by multiplex 'broad range' denaturing gradient gel electrophoresis. Mutations were identified by fluorescent automated sequencing or by restriction enzyme digestion analysis if an abnormal DGGE pattern was recognised. 21 different mutations were identified for 175 PKU chromosomes, with a mutation detection rate of 95%. The most common ones were R408W (73.5% chromosomes) and R158Q (7.0% chromosomes) whereas the remaining mutations appeared to be rare (relative frequencies 0.5%-2%). The high mutation detection rate obtained is an evidence of the efficiency of PAH genetic testing achieved in Lithuania. Moreover, the definition of the PKU mutation profile in the Lithuanian population will allow to perform a genotype-phenotype correlation study thus making feasible genotyped-based prediction of the biochemical phenotype in newborns with hyperphenylalaninemia. This may be useful for refining diagnosis and anticipating dietary requirements. PMID:12655550

  13. Multiple origins for phenylketonuria in Europe

    PubMed Central

    Eisensmith, R. C.; Okano, Y.; Dasovich, M.; Wang, T.; Güttler, F.; Lou, H.; Guldberg, P.; Lichter-Konecki, U.; Konecki, D. S.; Svensson, E.; Hagenfeldt, L.; Rey, F.; Munnich, A.; Lyonnet, S.; Cockburn, F.; Connor, J. M.; Pembrey, M. E.; Smith, I.; Gitzelmann, R.; Steinmann, B.; Apold, J.; Eiken, H. G.; Giovannini, M.; Riva, E.; Longhi, R.; Romano, C.; Cerone, R.; Naughten, E. R.; Mullins, C.; Cahalane, S.; Özalp, I.; Fekete, G.; Schuler, D.; Berencsi, G. Y.; Nász, I.; Brdicka, R.; Kamaryt, J.; Pijackova, A.; Cabalska, B.; Boszkowa, K.; Schwartz, E.; Kalinin, V. N.; Jin, L.; Chakraborty, R.; Woo, S. L. C.

    1992-01-01

    Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12nt1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population. PMID:1361100

  14. White Matter Integrity and Executive Abilities in Individuals with Phenylketonuria

    PubMed Central

    Antenor-Dorsey, Jo Ann V.; Hershey, Tamara; Rutlin, Jerrel; Shimony, Joshua S.; McKinstry, Robert C.; Grange, Dorothy K.; Christ, Shawn E.; White, Desirée A.

    2013-01-01

    Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes is poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU. PMID:23608077

  15. PHENYLKETONURIA, DETECTION IN THE NEWBORN INFANT AS A ROUTINE HOSPITAL PROCEDURE.

    ERIC Educational Resources Information Center

    GUTHRIE, ROBERT; WHITNEY, STEWART

    A FIELD TRIAL OF AN INHIBITION ASSAY METHOD FOR SCREENING FOR PHENYLKETONURIA (PKU) TESTED MORE THAN 400,000 NEWBORN INFANTS PRIOR TO DISCHARGE FROM THE HOSPTIAL. IN ALL, 39 CASES WERE FOUND, A HIGHER INCIDENCE THAN HAD PREVIOUSLY BEEN EXPECTED. THE PRACTICALITY OF THE INHIBITION ASSAY METHOD WAS ALSO DEMONSTRATED. THE REPORT DETAILS THE TRIAL'S…

  16. Loss of Intellectual Function in Children with Phenylketonuria after Relaxation of Dietary Phenylalanine Restriction.

    ERIC Educational Resources Information Center

    Seashore, Margretta R.; And Others

    1985-01-01

    Discontinuation at ages five to six of dietary restriction in 14 children with classic phenylketonuria (PKU--a metabolic disorder which, if untreated, is associated with mental retardation) resulted in deterioration in intellectual function for some of the Ss. Deficits included visual motor integration and cognitive problem solving. (CL)

  17. Phenylketonuria and the peoples of Northern Ireland.

    PubMed

    Zschocke, J; Mallory, J P; Eiken, H G; Nevin, N C

    1997-08-01

    The comparison of regional patterns of recessive disease mutations is a new source of information for studies of population genetics. The analysis of phenylketonuria (PKU) mutations in Northern Ireland shows that most major episodes of immigration have left a record in the modern genepool. The mutation 165T can be traced to the Palaeolithic people of western Europe who, in the Mesolithic period, first colonised Ireland. R408W (on haplotype 1) in contrast, the most common Irish PKU mutation, may have been prevalent in the Neolithic farmers who settled in Ireland after 4500 BC. No mutation was identified that could represent European Celtic populations, supporting the view that the adoption of Celtic culture and language in Ireland did not involve major migration from the continent. Several less common mutations can be traced to the Norwegian Atlantic coast and were probably introduced into Ireland by Vikings. This indicates that PKU has not been brought to Norway from the British Isles, as was previously argued. The rarity in Northern Ireland of IVS12nt1, the most common mutation in Denmark and England, indicates that the English colonialization of Ireland did not alter the local genepool in a direction that could be described as Anglo-Saxon. Our results show that the culture and language of a population can be independent of its genetic heritage, and give some insight into the history of the peoples of Northern Ireland. PMID:9254847

  18. Nutritional management of PKU with glycomacropeptide from cheese whey.

    PubMed

    Ney, D M; Gleason, S T; van Calcar, S C; MacLeod, E L; Nelson, K L; Etzel, M R; Rice, G M; Wolff, J A

    2009-02-01

    Individuals with phenylketonuria (PKU) must follow a lifelong low-phenylalanine (Phe) diet to prevent neurological impairment. Compliance with the low-Phe diet is often poor owing to restriction in natural foods and the requirement for consumption of a Phe-free amino acid formula or medical food. Glycomacropeptide (GMP), a natural protein produced during cheese-making, is uniquely suited to a low-Phe diet because when isolated from cheese whey it contains minimal Phe (2.5-5 mg Phe/g protein). This paper reviews progress in evaluating the safety, acceptability and efficacy of GMP in the nutritional management of PKU. A variety of foods and beverages can be made with GMP to improve the taste, variety and convenience of the PKU diet. Sensory studies in individuals with PKU demonstrate that GMP foods are acceptable alternatives to amino acid medical foods. Studies in the PKU mouse model demonstrate that GMP supplemented with limiting indispensable amino acids provides a nutritionally adequate source of protein and improves the metabolic phenotype by reducing concentrations of Phe in plasma and brain. A case report in an adult with classical PKU who followed the GMP diet for 10 weeks at home indicates safety, acceptability of GMP food products, a 13-14% reduction in blood Phe levels (p<0.05) and improved distribution of dietary protein throughout the day compared with the amino acid diet. In summary, food products made with GMP that is supplemented with limiting indispensable amino acids provide a palatable alternative source of protein that may improve dietary compliance and metabolic control of PKU. PMID:18956251

  19. An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

    ERIC Educational Resources Information Center

    Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

    2011-01-01

    Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

  20. Mutation Spectrum of Six Genes in Chinese Phenylketonuria Patients Obtained through Next-Generation Sequencing

    PubMed Central

    Cen, Zhong; Yu, Li; Lin, Lin; Hao, Jing; Yang, Zhigang; Peng, Jiabao; Cui, Shujian; Huang, Jian

    2014-01-01

    Background The identification of gene variants plays an important role in the diagnosis of genetic diseases. Methodology/Principal Findings To develop a rapid method for the diagnosis of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency, we designed a multiplex, PCR-based primer panel to amplify all the exons and flanking regions (50 bp average) of six PKU-associated genes (PAH, PTS, GCH1, QDPR, PCBD1 and GFRP). The Ion Torrent Personal Genome Machine (PGM) System was used to detect mutations in all the exons of these six genes. We tested 93 DNA samples from blood specimens from 35 patients and their parents (32 families) and 26 healthy adults. Using strict bioinformatic criteria, this sequencing data provided, on average, 99.14% coverage of the 39 exons at more than 70-fold mean depth of coverage. We found 23 previously documented variants in the PAH gene and six novel mutations in the PAH and PTS genes. A detailed analysis of the mutation spectrum of these patients is described in this study. Conclusions/Significance These results were confirmed by Sanger sequencing. In conclusion, benchtop next-generation sequencing technology can be used to detect mutations in monogenic diseases and can detect both point mutations and indels with high sensitivity, fidelity and throughput at a lower cost than conventional methods in clinical applications. PMID:24705691

  1. Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria.

    PubMed

    Sarkissian, Christineh N; Kang, Tse Siang; Gámez, Alejandra; Scriver, Charles R; Stevens, Raymond C

    2011-11-01

    Phenylketonuria (PKU), a Mendelian autosomal recessive phenotype (OMIM 261600), is an inborn error of metabolism causing impaired postnatal cognitive development in the absence of treatment. We used the Pah(enu2/enu2) PKU mouse model to study oral enzyme substitution therapy with various chemically modified formulations of phenylalanine ammonia lyase (Av-p.C503S/p.C565S/p.F18A PAL). In vivo studies with the most therapeutically effective formulation (5kDa PEG-Av-p.C503S/p.C565S/p.F18A PAL) revealed that this conjugate, given orally, yielded statistically significant (p=0.0029) and therapeutically relevant reduction (~40%) in plasma phenylalanine (Phe) levels. Phe reduction occurred in a dose- and loading-dependent manner; sustained clinically and statistically significant reduction of plasma Phe levels was observed with treatment ranging between 0.3 IU and 9 IU and with more frequent and smaller dosings. Oral PAL therapy could potentially serve as an adjunct therapy, perhaps with dietary treatment, and will work independently of phenylalanine hydroxylase (PAH), correcting such forms of hyperphenylalaninemias regardless of the PAH mutations carried by the patient. PMID:21803624

  2. Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria.

    PubMed

    Leuzzi, V; Bianchi, M C; Tosetti, M; Carducci, C L; Carducci, C A; Antonozzi, I

    2000-09-01

    Recent studies using in vivo proton magnetic resonance spectroscopy (1H MRS) have suggested that plasma phenylalanine (Phe) may not be a reliable indicator of brain Phe level in subjects with phenylketonuria (PKU). Interindividual variation in cerebral Phe can contribute to the phenotypic variability of the disease. We report the results of the direct assessment of brain Phe by 1H MRS in 10 off-diet PKU patients (aged 15.5-30.5 years), 4 detected and treated early, 6 late. In a single patient, brain Phe was evaluated before and 15 days after diet discontinuation. FLAIR MRI and 1H MRS were performed in the same setting by a 1.5 T clinical MR scanner. MR images were scored according to the extent of the lobar white-matter hyperintensity. Brain 1H MRS Phe signal (resonating at 7.36 ppm) was evaluated as a ratio to the creatine+phosphocreatine signal. Brain Phe was correlated with clinical, biochemical and MRI findings. Results were as follows. (1) An abnormal concentration of brain Phe was detected in all 10 PKU subjects (ranging from 0.030 to 0.074), associated with a wide interindividual variability of concurrent plasma Phe (ranging from 724 to 2800 micromol/L). (2) In late-detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. The discrepancy between brain and plasma Phe was relevant from a clinical point of view in two cases: in one, a late-detected patient with normal mental development, a high level of plasma Phe was associated with a relatively low concentration of brain Phe; in the other, a late-detected subject with severe neurological impairment, a very high level of brain Phe was associated with plasma Phe compatible with the diagnosis of mild PKU. (3) White-matter alterations were detected in all patients. FLAIR MRI sequences disclosed an involvement of optic chiasma and tracts in 7 subjects. No correlation was found between white-matter alterations and concurrent brain Phe concentrations. (4) In the only

  3. The Adolescent Adjustment Profile (AAP) in comparisons of patients with obesity, phenylketonuria or neurobehavioural disorders.

    PubMed

    Olsson, Gunilla Maria; Mårild, Staffan; Alm, Jan; Brodin, Ulf; Rydelius, Per-Anders; Marcus, Claude

    2008-01-01

    Psychosocial development in children with chronic disease is a key issue in paediatrics. This study investigated whether psychosocial adjustment could be reliably assessed with the 42-item Adolescent Adjustment Profile (AAP) instrument. The study mainly focused on adjustment-to-obesity measurement, although it compared three patient groups with chronic conditions. All phenylketonuria (PKU) patients in Sweden between ages 9 and 18 and their parents and teachers were invited to participate. Patients with neurobehavioural syndromes and obesity were age- and gender-matched with PKU patients. Healthy children constituted a reference group. Psychosocial adjustment was measured using the AAP, which is a multi-informant questionnaire that contains four domains. Information concerning parents' socio-economic and civil status was requested separately. Respondents to the three questionnaires judged the PKU patients to be normal in all four domains. Patients with neurobehavioural syndromes demonstrated less competence and the most problems compared with the other three groups. According to the self-rating, the parent rating and the teacher rating questionnaires, obese patients had internalizing problems. The parent rating and the teacher rating questionnaire scored obese patients as having a lower work capacity than the reference group. Compared with the reference group, not only families with obese children but also families with children with neurobehavioural syndromes had significantly higher divorce rates. Obese patients were also investigated with the Strength and Difficulties Questionnaire (SDQ), another instrument that enables comparison between two measures of adjustment. The AAP had good psychometric properties; it was judged a useful instrument in research on adolescents with chronic diseases. PMID:18389428

  4. How Is PKU Monitored?

    MedlinePlus

    ... people with PKU. The visit should include a blood draw, a short exam by a pediatrician, and a chance to discuss ways to manage the low-phe food pattern. The nutrition education activity for children and parent ...

  5. [Blood somatomedin levels in neonates with congenital hypothyroidism and phenylketonuria].

    PubMed

    Hníková, O; Hejcmanová, L; Marek, J; Schreiberová, O

    1991-12-01

    A biological method was employed for assessing the somatomedin activity (SM)-IGF I-somatomedin C: 1) in 13 10 to 23-day old children with congenital hypothyroidism (CH) before starting substitution therapy with L-thyroxine and after one month lasting therapy. SM levels were significantly lower prior to the onset of therapy than in a control group (for p less than 0.01 on 1% level). The SM levels in treated children did not differ from controls. 2) 16 children with classic phenylketonuria (PKU) were also examined of the age of 12-23 days before starting dietary treatment with restricted phenylalanine (Phe). When compared with a control group SM levels were significantly lower in the PKU group (p = 0.01 on 5% level). When stable serum Phe concentrations had been obtained, following restricted Phe intake, SM levels no longer differed from the control. However statistical correlation of Phe and SM levels was not attained. PMID:1806267

  6. Age-Related Psychophysiological Vulnerability to Phenylalanine in Phenylketonuria

    PubMed Central

    Leuzzi, Vincenzo; Mannarelli, Daniela; Manti, Filippo; Pauletti, Caterina; Locuratolo, Nicoletta; Carducci, Carla; Carducci, Claudia; Vanacore, Nicola; Fattapposta, Francesco

    2014-01-01

    Background: Phenylketonuria (PKU) is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). Neonatal screening programs and early treatment have radically changed the natural history of PKU. Nevertheless, an increased risk of neurocognitive and psychiatric problems in adulthood remains a challenging aspect of the disease. In order to assess the vulnerability of complex skills to Phe, we explored: (a) the effect of a rapid increase in blood Phe levels on event-related potentials (ERP) in PKU subjects during their second decade of life; (b) the association (if existing) between psychophysiological and neurocognitive features. Methods: Seventeen early-treated PKU subjects, aged 10–20, underwent ERP [mismatch negativity, auditory P300, contingent negative variation (CNV), and Intensity Dependence of Auditory Evoked Potentials] recording before and 2 h after an oral loading of Phe. Neurocognitive functioning, historical and concurrent biochemical values of blood Phe, Tyr, and Phe/Tyr ratio, were all included in the statistical analysis. Results: Event-related potential components were normally detected in all the subjects. In subjects younger than 13 CNV amplitude, W2-CNV area, P3b latency, and reaction times in motor responses were negatively influenced by Phe-loading. Independently from the psychophysiological vulnerability, some neurocognitive skills were more impaired in younger patients. No correlation was found between biochemical alterations and neurocognitive and psychophysiological findings. Conclusion: The vulnerability of the emerging neurocognitive functions to Phe suggests a strict metabolic control in adolescents affected by PKU and a neurodevelopmental approach in the study of neurocognitive outcome in PKU. PMID:25003100

  7. Phenylketonuria: Direct and indirect effects of phenylalanine.

    PubMed

    Schlegel, Gudrun; Scholz, Ralf; Ullrich, Kurt; Santer, René; Rune, Gabriele M

    2016-07-01

    High phenylalanine concentrations in the brain due to dysfunctional phenylalanine hydroxylase (Pah) are considered to account for mental retardation in phenylketonuria (PKU). In this study, we treated hippocampal cultures with the amino acid in order to determine the role of elevated levels of phenylalanine in PKU-related mental retardation. Synapse density and dendritic length were dramatically reduced in hippocampal cultures treated with phenylalanine. Changes in cofilin expression and phosphorylation status, which were restored by NMDA, as well as reduced activation of the small GTPase Rac1, likely underlie these structural alterations. In the Pah(enu2) mouse, which carries a mutated Pah gene, we previously found higher synaptic density due to delayed synaptic pruning in response to insufficient microglia function. Microglia activity and C3 complement expression, both of which were reduced in the Pah(enu2) mouse, however, were unaffected in hippocampal cultures treated with phenylalanine. The lack of a direct effect of phenylalanine on microglia is the key to the opposite effects regarding synapse stability in vitro and in the Pah(enu2) mouse. Judging from our data, it appears that another player is required for the inactivation of microglia in the Pah(enu2) mouse, rather than high concentrations of phenylalanine alone. Altogether, the data underscore the necessity of a lifelong phenylalanine-restricted diet. PMID:27091224

  8. Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino Acid-based medical foods for nutrition management of phenylketonuria.

    PubMed

    van Calcar, Sandra C; Ney, Denise M

    2012-08-01

    Phenylketonuria (PKU), an inborn error in phenylalanine metabolism, requires lifelong nutrition management with a low-phenylalanine diet, which includes a phenylalanine-free amino acid-based medical formula to provide the majority of an individual's protein needs. Compliance with this diet is often difficult for older children, adolescents, and adults with PKU. The whey protein glycomacropeptide (GMP) is ideally suited for the PKU diet because it is naturally low in phenylalanine. Nutritionally complete, acceptable medical foods and beverages can be made with GMP to increase the variety of protein sources for the PKU diet. As an intact protein, GMP improves protein use and increases satiety compared with amino acids. Thus, GMP provides a new, more physiologic source of low-phenylalanine dietary protein for people with PKU. PMID:22818728

  9. Alternative therapies to address the unmet medical needs of patients with phenylketonuria.

    PubMed

    Blau, Nenad; Longo, Nicola

    2015-04-01

    Standard therapy for phenylketonuria (PKU), the most common inherited disorder in amino acid metabolism, is an onerous phenylalanine-restricted diet. Adherence to this stringent diet regimen decreases as patients get older, and this lack of adherence is directly associated with cognitive and executive dysfunction and psychiatric issues. These factors emphasize the need for alternative pharmacological therapies to help treat patients with PKU. Sapropterin dihydrochloride is a synthetic form of tetrahydrobiopterin, the cofactor of phenylalanine hydroxylase that in pharmacological doses can stabilize and increase residual enzyme activity in some patients with PKU. About one-third of all patients with PKU respond to oral sapropterin. Phenylalanine ammonia lyase (PAL) is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Phase I and II trials have shown that injectable recombinant Anabaena variabilis PAL produced in Escherichia coli conjugated with PEG can reduce phenylalanine levels in subjects with PKU. The most frequently reported adverse events were injection-site reactions, dizziness and immune reactions. Additionally, oral administration of PAL and delivery of enzyme substitution therapies by encapsulation in erythrocytes are being investigated. Novel therapies for patients with PKU appear to be options to reduce phenylalanine levels, and may reduce the deleterious effects of this disorder. PMID:25660215

  10. Barriers to dietary control among pregnant women with phenylketonuria--United States, 1998-2000.

    PubMed

    2002-02-15

    Newborns in the United States are screened for phenylketonuria (PKU), a metabolic disorder that when left untreated is characterized by elevated blood phenylalanine (phe) levels and severe mental retardation (MR). An estimated 3,000-4,000 U.S.-born women of reproductive age with PKU have not gotten severe MR because as newborns their diets were severely restricted in the intake of protein-containing foods and were supplemented with medical foods (e.g., amino acid-modified formula and modified low-protein foods). When women with PKU do not adhere to their diet before and during pregnancy, infants born to them have a 93% risk for MR and a 72% risk for microcephaly. These risks result from the toxic effects of high maternal blood phe levels during pregnancy, not because the infant has PKU. The restricted diet, which should be maintained for life, often is discontinued during adolescence. This report describes the pregnancies of three women with PKU and underscores the importance of overcoming the barriers to maintaining the recommended dietary control of blood phe levels before and during pregnancy. For maternal PKU-associated MR to be prevented, studies are needed to determine effective approaches to overcoming barriers to dietary control. PMID:11898925

  11. A Systematic Review of Bone Mineral Density and Fractures in Phenylketonuria

    PubMed Central

    Hansen, Karen E.; Ney, Denise

    2014-01-01

    Introduction Our objective was to systematically review and analyze published data on bone mineral density (BMD) and fracture rates in patients with phenylketonuria (PKU), and relationships between BMD and phenylalanine levels. Methodology We searched PubMed, CINAHL and Cochrane databases from January 1966 to November 2013 for studies of spine BMD or fracture in PKU and control subjects. We excluded studies assessing skeletal health by ultrasound or peripheral quantitative computer tomography. Both authors reviewed abstracts for inclusion, and read full text papers to extract data. Results Sixteen studies met eligibility criteria. Meta-analysis of 3 studies found that spine BMD was 0.100 g/cm2 lower (95% CI, −0.110, −0.090 g/cm2) in 67 subjects with PKU, compared to 161 controls. Among 6 studies, 20% (53 of 263) of PKU subjects experienced clinical fractures. In the single study with controls, the fracture rate was 2.6 fold higher (95% CI, 1.1–6.1) after age 8 in PKU subjects, compared to healthy sibling controls. When considering a total of 12 studies in 412 subjects, 9 or 75% of studies representing 71% of studied subjects reported no association between phenylalanine levels and BMD. Summary Spine BMD is lower in PKU than control subjects, but only one study controlled for smaller body size. Existing studies suggest a clinical fracture rate of 20% among PKU subjects, but fracture rates in controls are lacking. Finally, existing data shows no consistent relationship between phenylalanine levels and BMD. Future studies are needed to clarify the etiology and health consequences of low BMD in PKU. PMID:25005329

  12. The Use of Glycomacropeptide in Dietary Management of Phenylketonuria

    PubMed Central

    Zaki, Osama K.; El-Wakeel, Lamia; Ebeid, Yasmin; Ez Elarab, Hanan S.; Moustafa, Aisha; Abdulazim, Nayera; Karara, Hala; Elghawaby, Ahmed

    2016-01-01

    Dietary therapy is the most common therapy applied in treatment of Phenylketonuria (PKU) with restriction of intake of most natural proteins that are rich in Phenylalanine (Phe). Recently, it has been claimed that caseinoglycomacropeptide (GMP), derived of whey, may be used to replace the amino acid formulae (AAF). The Aim of Work. To study the feasibility of use of GMP for partial replacement of artificial formula in treatment of children with PKU. Methods. Ten patients with PKU were included in the study. They received the recommended daily allowances of protein in the form of AAF or a combination of AAF and GMP. The percent of intake of GMP in phases 1 and 2 was 50% and zero%, respectively. Results. The median and interquartiles of phenyl alanine Phe levels phase were not significantly different in phases I and II, 376 (167–551) μmol/L versus 490 (289–597) μmol/L, respectively. Phenylalanine/tyrosine ratio, amino acids, and other laboratory data showed no significant difference between the two phases. Conclusion. GMP may be used to replace 50% of the protein intake to improve the nutritive value and palatability of diet and to provide a more satisfactory diet. No toxicity or side effects were reported in patients on that regimen. PMID:27313877

  13. Phenylketonuria: a review of current and future treatments

    PubMed Central

    Al Hafid, Naz

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  14. Phenylketonuria: a review of current and future treatments.

    PubMed

    Al Hafid, Naz; Christodoulou, John

    2015-10-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  15. Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing

    PubMed Central

    Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Schwartz, Ida Vanessa Doederlein

    2016-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

  16. Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.

    PubMed

    Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Roesch, Luiz Fernando Würdig; Schwartz, Ida Vanessa Doederlein

    2016-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

  17. Large Neutral Amino Acid Supplementation Exerts Its Effect through Three Synergistic Mechanisms: Proof of Principle in Phenylketonuria Mice

    PubMed Central

    van Vliet, Danique; Bruinenberg, Vibeke M.; Mazzola, Priscila N.; van Faassen, Martijn H. J. R.; de Blaauw, Pim; Kema, Ido P.; Heiner-Fokkema, M. Rebecca; van Anholt, Rogier D.; van der Zee, Eddy A.; van Spronsen, Francjan J.

    2015-01-01

    Background Phenylketonuria (PKU) was the first disorder in which severe neurocognitive dysfunction could be prevented by dietary treatment. However, despite this effect, neuropsychological outcome in PKU still remains suboptimal and the phenylalanine-restricted diet is very demanding. To improve neuropsychological outcome and relieve the dietary restrictions for PKU patients, supplementation of large neutral amino acids (LNAA) is suggested as alternative treatment strategy that might correct all brain biochemical disturbances caused by high blood phenylalanine, and thereby improve neurocognitive functioning. Objective As a proof-of-principle, this study aimed to investigate all hypothesized biochemical treatment objectives of LNAA supplementation (normalizing brain phenylalanine, non-phenylalanine LNAA, and monoaminergic neurotransmitter concentrations) in PKU mice. Methods C57Bl/6 Pah-enu2 (PKU) mice and wild-type mice received a LNAA supplemented diet, an isonitrogenic/isocaloric high-protein control diet, or normal chow. After six weeks of dietary treatment, blood and brain amino acid and monoaminergic neurotransmitter concentrations were assessed. Results In PKU mice, the investigated LNAA supplementation regimen significantly reduced blood and brain phenylalanine concentrations by 33% and 26%, respectively, compared to normal chow (p<0.01), while alleviating brain deficiencies of some but not all supplemented LNAA. Moreover, LNAA supplementation in PKU mice significantly increased brain serotonin and norepinephrine concentrations from 35% to 71% and from 57% to 86% of wild-type concentrations (p<0.01), respectively, but not brain dopamine concentrations (p = 0.307). Conclusions This study shows that LNAA supplementation without dietary phenylalanine restriction in PKU mice improves brain biochemistry through all three hypothesized biochemical mechanisms. Thereby, these data provide proof-of-concept for LNAA supplementation as a valuable alternative dietary

  18. A comparison of phenylketonuria with attention deficit hyperactivity disorder: do markedly different aetiologies deliver common phenotypes?

    PubMed

    Stevenson, M; McNaughton, N

    2013-10-01

    Phenylketonuria (PKU) is a well-defined metabolic disorder arising from a mutation that disrupts phenylalanine metabolism and so produces a variety of neural changes indirectly. Severe cognitive impairment can be prevented by dietary treatment; however, residual symptoms may be reported. These residual symptoms appear to overlap a more prevalent childhood disorder: Attention Deficit/Hyperactivity Disorder (ADHD). However, the aetiology of ADHD is a vast contrast to PKU: it seems to arise from a complex combination of genes; and it has a substantial environmental component. We ask whether these two disorders result from two vastly different genotypes that converge on a specific core phenotype that includes similar dysfunctions of Gray's (Gray, 1982) Behavioural Inhibition System (BIS), coupled with other disorder-specific dysfunctions. If so, we believe comparison of the commonalities will allow greater understanding of the neuropsychology of both disorders. We review in detail the aetiology, treatment, neural pathology, cognitive deficits and electrophysiological abnormalities of PKU; and compare this with selected directly matching aspects of ADHD. The biochemical and neural pathologies of PKU and ADHD are quite distinct in their causes and detail; but they result in the disorder in the brain of large amino acid levels, dopamine and white matter that are very similar and could explain the overlap of symptoms within and between the PKU and ADHD spectra. The common deficits affect visual function, motor function, attention, working memory, planning, and inhibition. For each of PKU and ADHD separately, a subset of deficits has been attributed to a primary dysfunction of behavioural inhibition. In the case of ADHD (excluding the inattentive subtype) this has been proposed to involve a specific failure of the BIS; and we suggest that this is also true of PKU. This accounts for a substantial proportion of the parallels in the superficial symptoms of both disorders and

  19. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation

    PubMed Central

    Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

    2015-01-01

    Background and Purpose Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. Methods In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMT mean was defined as the mean value of the sum of CIMT left and CIMT right. Results Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Conclusions Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients. PMID:26291823

  20. The rehabilitation programme of an adult phenylketonuria with upper motor neuron involvement.

    PubMed

    Soyupek, Feray; Koyuncuoglu, Hasan; Cindas, Abdullah; Ilgun, Erdem; Tak, Rukiye

    2009-01-01

    Phenylketonuria (PKU) is a disorder characterized by several biochemical mechanisms which may impair the brain functions in PKU, leading to neurological problems. Our case report concerns a 19 year-old man with phenylketonuria who was evaluated with the onset of stiffness following the abandonment of the phenylalanine-restricted diet. He was assessed with grade-4 spasticity according to Modified Aschworth scale. The deep tendon reflexes had increased and the plantar reflexes were positive. Knee extensions were limited due to the shortening of the hamstring muscles. Serum phenylalanine concentration was elevated and plasma vitamin B12 level was low. Cranial magnetic resonance imaging scan revealed demyelinization area in periventricular deep white matter. We administered a phenylalanine-restricted diet and a rehabilitation program. Following the treatment, spasticity was reduced to grade-1 and patient could walk without aid. This case shows that, the combination of diet, medication and a rehabilitation program is an effective treatment model on adult PKU with upper motor neuron involvement. PMID:20023364

  1. The discovery of phenylketonuria: the story of a young couple, two retarded children, and a scientist.

    PubMed

    Centerwall, S A; Centerwall, W R

    2000-01-01

    In the 1920s, a little girl 3 years of age was brought from China to the United States by her American mother. Although the child was beautiful, her mind was not developing. The grief-stricken mother had consulted doctors in China, but they could neither diagnose the problem nor provide treatment. Morning and night the same questions occupied her mind: "What is the matter with my little girl? What is causing it? Is there any doctor, anywhere, who can cure her?" In the United States, she also went from doctors to psychologists to clinics looking for someone who could help. Finally, she went to the Mayo Clinic in Rochester, Minnesota. When she had answered all of the doctor's questions, and all the tests were finished, they still could not tell her what was wrong. There was nothing they could do. The disease from which the little girl suffered was unknown at that time. The mother was Pearl Buck. In her book, The Child Who Never Grew,(1) she described her first infant: "I remember when she was only 3 months old she lay in her basket on the sun deck of a ship. I had taken her there for the morning air. The people who promenaded on deck often stopped to look at her, and my pride grew as they spoke of her unusual beauty and of the intelligent look of her deep, blue eyes. I do not know at what moment the growth of her intelligence stopped, nor to this day why it did." This is a classical description of the disease, phenylketonuria (PKU). A perfect infant seems to develop normally for several months, then the development slows and at some point seems to stop. "Look at Mommy-look at Daddy!" the parents say as they try to coax the treasured smiles. Instead, the child drifts into a dream world and into irreversible mental retardation. All Pearl Buck's devotion and determination was of no avail in finding the cause of her child's retardation. It was to be another mother with the same commitment to her beautiful but retarded children, who approximately 10 years later followed

  2. Intra-familiar discordant PKU phenotype explained by mutation analysis in three pedigrees.

    PubMed

    Trunzo, Roberta; Santacroce, Rosa; D'Andrea, Giovanna; Longo, Vittoria; De Girolamo, Giuseppe; Dimatteo, Claudia; Leccese, Angelica; Lillo, Vincenza; Papadia, Francesco; Margaglione, Maurizio

    2014-02-01

    Classical phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are two phenotypes of phenylalanine hydroxylase (PAH) deficiency with different degrees of severity. We have analyzed three families in which classical PKU, MHP and a normal phenotype occurred within each family due to the different combinations of three mutations segregating within the family. Indeed, sequence PAH analysis revealed three different alleles segregating in each family. This report suggests that when discordant phenotypes occur in a family, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counseling and patient management. We further support the marked heterogeneity of hyperphenylalaninemia primarily due to allelic heterogeneity at the PAH locus. PMID:24296287

  3. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

    PubMed

    Diamond, A; Prevor, M B; Callender, G; Druin, D P

    1997-01-01

    To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed. PMID:9421921

  4. PKU Self-Management Timeline

    MedlinePlus

    ... language skills and becomes more interested in his environment, it will be time for him to have a role in his own PKU management. Thankfully, this process can be quite natural. One of the parents in our clinic has ...

  5. Methylome repatterning in a mouse model of Maternal PKU Syndrome.

    PubMed

    Dobrowolski, S F; Lyons-Weiler, J; Biery, A; Spridik, K; Vockley, G; Kranik, E; Skvorak, K; Sultana, T

    2014-11-01

    Maternal PKU Syndrome (MPKU) is an embryopathy resulting from in utero phenylalanine (PHE) toxicity secondary to maternal phenylalanine hydroxylase deficient phenylketonuria (PKU). Clinical phenotypes in MPKU include mental retardation, microcephaly, in utero growth restriction, and congenital heart defects. Numerous in utero toxic exposures alter DNA methylation in the fetus. The PAH(enu2) mouse is a model of classical PKU while offspring born of hyperphenylalaninemic dams model MPKU. We investigated offspring of PAH(enu2) dams to determine if altered patterns of DNA methylation occurred in response to in utero PHE exposure. As neurologic deficit is the most prominent MPKU phenotype, methylome patterns were assessed in brain tissue using methylated DNA immunoprecipitation and paired-end sequencing. Brain tissues were assessed in E18.5-19 fetuses of PHE unrestricted PAH(enu2) dams, PHE restricted PAH(enu2) dams, and heterozygous(wt/enu2) control dams. Extensive methylome repatterning was observed in offspring of hyperphenylalaninemic dams while the offspring of PHE restricted dams displayed attenuated methylome repatterning. Methylation within coding regions was dominated by noncoding RNA genes. Differential methylation of promoters targeted protein coding genes. To assess the impact of methylome repatterning on gene expression, brain tissue in experimental and control animals were queried with microarrays assessing expression of microRNAs and protein coding genes. Altered expression of methylome-modified microRNAs and protein coding genes was extensive in offspring of hyperphenylalaninemic dams while minimal changes were observed in offspring of PHE restricted dams. Several genes displaying significantly reduced expression have roles in neurological function or genetic disease with neurological phenotypes. These data indicate in utero PHE toxicity alters DNA methylation in the brain which has downstream impact upon gene expression. Altered gene expression may

  6. Phenylketonuria: dietary and therapeutic challenges.

    PubMed

    Giovannini, M; Verduci, E; Salvatici, E; Fiori, L; Riva, E

    2007-04-01

    PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC-PUFAs, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and 'modulated' amino acid preparations might help in preventing nutritional deficiencies and imbalances, with the ultimate aim of improving growth. New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes. PMID:17347911

  7. Characterization of phenylalanine hydroxylase gene mutations in phenylketonuria in Xinjiang of China

    PubMed Central

    Yu, Wuzhong; He, Jiang; Yang, Xi; Zou, Hongyun; Gui, Junhao; Wang, Rui; Yang, Liu; Wang, Zheng; Lei, Quan

    2014-01-01

    To investigate the spectrum and frequency of phenylalanine hydroxylase (PAH) gene mutations in phenylketonuria (PKU) patients in Xinjiang, China. Polymerase chain reaction (PCR), in combination with single-strand conformation polymorphism (SSCP) and DNA sequencing analyses were performed, to screen potential mutations in the PAH gene in 46 individual PKU patients. Direct DNA sequencing was used to analyze the all of the exons in the PAH gene, including the promoter and flanking intron regions, in another 15 PKU patients. Our results indicated that, 30 different mutation types were identified in all 122 PAH alleles, with the mutation detection rate of 78.7% (96/122). Four novel mutations, i.e., 5’-Flanking -626G>A, 5’-Flanking -480DelACT, S196fsX4, and IVS8+1G>C, were identified for the first time. Similar to other regions in North China, R243Q, EX6-96A>G, IVS4-1A>G, R111X, and Y356X were the most prevalent PAH mutations in PKU patients from Xinjiang. Additionally, common mutations showed different frequencies in Xinjiang, when compared to other areas. Furthermore, sixteen different PAH gene mutation types were identified for the first time in the minorities in Xinjiang. Distinctive mutation spectrum of PAH gene in PKU patients from Xinjiang were characterized, which may promote the construction of PAH gene mutation database and serve as valuable tools for genetic diagnosis and counseling, and prognostic evaluation for PKU cases in the local area. PMID:25550961

  8. Phone-based motivational interviewing to increase self-efficacy in individuals with phenylketonuria

    PubMed Central

    Viau, Krista S.; Jones, Jessica L.; Murtaugh, Maureen A.; Gren, Lisa H.; Stanford, Joseph B.; Bilder, Deborah A.

    2016-01-01

    Objective To measure change in patient activation and self-efficacy in individuals with phenylketonuria (PKU) before and after a 6-month phone-based motivational interviewing (MI) intervention and determine the feasibility of implementing dietary counseling for PKU using an MI approach. Methods Participants (n = 31) included preadolescents (7–12 years), adolescents (13–17 years), and adults (18–35 years) with early-treated PKU. Participants completed online questionnaires assessing self-reported stage of change (SOC), patient activation, and self-efficacy for PKU self-management behaviors. The intervention included monthly phone-based dietary counseling using MI during which participants set monthly goals. Results Patient activation and self-efficacy were significantly different by age group (both p < 0.01) with higher scores in older participants. Self-efficacy significantly increased from baseline to month 6 among adolescents and adults (7.4 ± 1.9 and 8.6 ± 1.3, respectively, p = 0.002). Preadolescents did not have a significant change in self-efficacy (p = 0.79). There was no increase in patient activation for preadolescents or adolescents/adults (p = 0.19 and p = 0.24, respectively). Indicators of learning problems were not significantly associated with self-efficacy (p = 0.33) or patient activation (p = 0.83). Conclusion These results demonstrate the feasibility of implementing phone-based dietary counseling for PKU using MI. This study also supports further investigation of MI as an intervention approach to improving self-efficacy and self-management behaviors in adolescents and adults with PKU. PMID:27014576

  9. Predictive equations underestimate resting energy expenditure in female adolescents with phenylketonuria

    PubMed Central

    Quirk, Meghan E.; Schmotzer, Brian J.; Schmotzer, Brian J.; Singh, Rani H.

    2010-01-01

    Resting energy expenditure (REE) is often used to estimate total energy needs. The Schofield equation based on weight and height has been reported to underestimate REE in female children with phenylketonuria (PKU). The objective of this observational, cross-sectional study was to evaluate the agreement of measured REE with predicted REE for female adolescents with PKU. A total of 36 females (aged 11.5-18.7 years) with PKU attending Emory University’s Metabolic Camp (June 2002 – June 2008) underwent indirect calorimetry. Measured REE was compared to six predictive equations using paired Student’s t-tests, regression-based analysis, and assessment of clinical accuracy. The differences between measured and predicted REE were modeled against clinical parameters to determine to if a relationship existed. All six selected equations significantly under predicted measured REE (P< 0.005). The Schofield equation based on weight had the greatest level of agreement, with the lowest mean prediction bias (144 kcal) and highest concordance correlation coefficient (0.626). However, the Schofield equation based on weight lacked clinical accuracy, predicting measured REE within ±10% in only 14 of 36 participants. Clinical parameters were not associated with bias for any of the equations. Predictive equations underestimated measured REE in this group of female adolescents with PKU. Currently, there is no accurate and precise alternative for indirect calorimetry in this population. PMID:20497783

  10. Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing

    PubMed Central

    Li, Nana; Jia, Haitao; Liu, Zhen; Tao, Jing; Chen, Song; Li, Xiaohong; Deng, Ying; Jin, Xi; Song, Jiaping; Zhang, Liangtao; Liang, Yu; Wang, Wei; Zhu, Jun

    2015-01-01

    Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism, mainly caused by a deficiency of phenylalanine hydroxylase (PAH). The incidence of various PAH mutations differs among race and ethnicity. Here we report a spectrum of PAH mutations complied from 796 PKU patients from mainland China. The all 13 exons and adjacent intronic regions of the PAH gene were determined by next-generation sequencing. We identified 194 different mutations, of which 41 are not reported before. Several mutations reoccurred with high frequency including p.R243Q, p.EX6-96A > G, p.V399V, p.R241C, p.R111*, p.Y356*, p.R413P, and IVS4-1G > A. 76.33% of mutations were localized in exons 3, 6, 7, 11, 12. We further compared the frequency of each mutation between populations in northern and southern China, and found significant differences in 19 mutations. Furthermore, we identified 101 mutations that are not reported before in Chinese population, our study thus broadens the mutational spectrum of Chinese PKU patients. Additionally, 41 novel mutations will expand and improve PAH mutation database. Finally, our study offers proof that NGS is effective, reduces screening times and costs, and facilitates the provision of appropriate genetic counseling for PKU patients. PMID:26503515

  11. Psychosocial issues and outcomes in maternal PKU.

    PubMed

    Koch, Richard; Trefz, Friedrich; Waisbren, Susan

    2010-01-01

    Elevated phenylalanine (Phe) levels in pregnant women with PKU are teratogenic. Fetal damage due to elevated maternal Phe levels during pregnancy is known as maternal phenylketonuria (MPKU). The risk of birth defects in MPKU, including global developmental delays, microcephaly, congenital heart disease, and low birth weight, can be dramatically reduced by controlling Phe levels during pregnancy (metabolic control). Phe levels should be maintained in the range of 120-360 micromol/L, ideally starting before pregnancy begins (i.e., when planning a pregnancy). If control is not achieved before pregnancy (e.g., if the pregnancy was unplanned), good outcomes are still possible if metabolic control is established by 8 weeks of pregnancy. Unfortunately, metabolic control before and during pregnancy can be poor. As well, many mothers stop treatment after pregnancy, which can decrease the mother's ability to focus on her child and increase her risk of behavioral and psychological problems. This can have a negative effect on the home environment. Many factors affect adherence to the strict diet used to control Phe levels, including poor access to medical care, lack of reimbursement for medical foods (in some regions, such as parts of the United States), practical difficulties with implementing the diet, financial constraints, demographics, and psychosocial issues. A comprehensive treatment approach that begins prior to pregnancy and continues after the infant is born may help to improve the management of MPKU. This approach should include education of girls about MPKU at an early age, interventions to prevent unplanned pregnancies, psychosocial support, improved treatment access and reimbursement for medical foods, and treatment guidelines. Treatments such as sapropterin may also have a role in improving metabolic control during pregnancy. PMID:20123474

  12. Genetic background of clinical homogeneity of phenylketonuria in Poland.

    PubMed Central

    Jaruzelska, J; Matuszak, R; Lyonnet, S; Rey, F; Rey, J; Filipowicz, J; Borski, K; Munnich, A

    1993-01-01

    In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (< 1%), and G272ter (< 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene. PMID:8097262

  13. Depression and anxiety among parents of phenylketonuria children

    PubMed Central

    Gunduz, Mehmet; Arslan, Nur; Unal, Ozlem; Cakar, Sevim; Kuyum, Pınar; Bulbul, Selda F.

    2015-01-01

    Objective: To investigate the existence of depression and/or anxiety with underlying risk factors among parents of children with classical phenylketonuria (PKU). Methods: This cross-sectional study was conducted in the Division of Pediatric Metabolism, Ankara Children’s Hospital, Dokuz Eylul University, Kırıkkale University, and Erzurum Local Research Hospital, Turkey, between January and July 2014. Parents of 61 patients and 36 healthy controls completed the self-report questionnaires. We used Beck Depression Inventory (BDI) to assess the parental depression and State-Trait Anxiety Inventory S-T (STAI S-T) to assess parental anxiety. Results: Depression and anxiety scores were significantly higher in the case group (BDI 12.3±9.1; STAI-S: 38.2±9.6; STAI-T: 43.2±6.9) than controls (BDI: 5.4±4.1 p=0.000; STAI-S: 31.8±7.6 p=0.001; STAI-T: 37.0±7.2 p=0.000). Mothers of the patients had higher scores than the other parental groups (BDI: p=0.000, STAI-S: p=0.001 and STAI-T: p=0.000). Logistic regression analysis showed that low educational level of the parent was the only independent factor for depression (OR 9.96, 95% CI: 1.89-52.35, p=0.007) and state anxiety (OR: 6.99, 95% CI: 1.22-40.48, p=0.030) in the case group. Conclusion: A subset of parents with PKU patients have an anxiety or depressive disorder. Supportive services dealing with the parents of chronically ill children such as PKU are needed in order to reduce the level of anxiety. PMID:26492114

  14. 5-Hydroxytryptophan during critical postnatal period improves cognitive performances and promotes dendritic spine maturation in genetic mouse model of phenylketonuria

    PubMed Central

    Andolina, Diego; Conversi, David; Cabib, Simona; Trabalza, Antonio; Ventura, Rossella; Puglisi-Allegra, Stefano; Pascucci, Tiziana

    2011-01-01

    Although phenylketonuria (PKU) is the most common genetic cause of mental retardation, the cellular mechanisms underlying impaired brain function are still unclear. Using PAHenu2 mice (ENU2), the genetic mouse model of PKU, we previously demonstrated that high phenylalanine levels interfere with brain tryptophan hydroxylase activity by reducing the availability of serotonin (5-hydroxytryptamine, 5-HT), crucial for maturation of neuronal connectivity in the prefrontal cortex (PFC), around the third postnatal week, a critical period for cortical maturation. 5-Hydroxytryptophan (5-HTP), the product of tryptophan hydroxylation, is known to be a better treatment to increase brain 5-HT levels. In this study we investigated the role of 5-HT during the early postnatal period in cognitive disturbances and in cortical dendritic alterations of PKU subjects by restoring temporarily (postnatal days 14–21) physiological brain levels of 5-HT in ENU2 through 5-HTP treatment. In adult ENU2 mice early 5-HTP treatment reverses cognitive deficits in spatial and object recognition tests accompanied by an increase in spine maturation of pyramidal neurons in layer V of the prelimbic/infralimbic area of the PFC, although locomotor deficits are not recovered by treatment. Taken together, our results support the hypothesis that mental retardation in PKU depends on reduced availability of brain 5-HT during critical developmental periods that interferes with cortical maturation and point to 5-HTP supplementation as a highly promising additional tool to heal PKU patients. PMID:21040618

  15. Low Bone Strength Is a Manifestation of Phenylketonuria in Mice and Is Attenuated by a Glycomacropeptide Diet

    PubMed Central

    Solverson, Patrick; Murali, Sangita G.; Litscher, Suzanne J.; Blank, Robert D.; Ney, Denise M.

    2012-01-01

    Purpose Phenylketonuria (PKU), caused by phenylalanine (phe) hydroxylase loss of function mutations, requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP), a low-phe whey protein, provides a palatable alternative to AA formula. Skeletal fragility is a poorly understood chronic complication of PKU. We sought to characterize the impact of the PKU genotype and dietary protein source on bone biomechanics. Procedures Wild type (WT; Pah+/+) and PKU (Pahenu2/enu2) mice on a C57BL/6J background were fed high-phe casein, low-phe AA, and low-phe GMP diets between 3 to 23 weeks of age. Following euthanasia, femur biomechanics were assessed by 3-point bending and femoral diaphyseal structure was determined. Femoral ex vivo bone mineral density (BMD) was assessed by dual-enengy x-ray absorptiometry. Whole bone parameters were used in prinicipal component analysis. Data were analyzed by 3-way ANCOVA with genotype, sex, and diet as the main factors. Findings Regardless of diet and sex, PKU femora were more brittle, as manifested by lower post-yield displacement, weaker, as manifested by lower energy and yield and maximal loads, and showed reduced BMD compared with WT femora. Four principal components accounted for 87% of the variance and all differed significantly by genotype. Regardless of genotype and sex, the AA diet reduced femoral cross-sectional area and consequent maximal load compared with the GMP diet. Conclusions Skeletal fragility, as reflected in brittle and weak femora, is an inherent feature of PKU. This PKU bone phenotype is attenuated by a GMP diet compared with an AA diet. PMID:23028819

  16. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria.

    PubMed

    Bruinenberg, Vibeke M; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C; Kuhn, Mirjam; van Spronsen, Francjan J; van der Zee, Eddy A

    2016-01-01

    The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice. PMID:27102170

  17. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria

    PubMed Central

    Bruinenberg, Vibeke M.; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C.; Kuhn, Mirjam; van Spronsen, Francjan J.; van der Zee, Eddy A.

    2016-01-01

    The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice. PMID:27102170

  18. A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria.

    PubMed

    Burton, B; Grant, M; Feigenbaum, A; Singh, R; Hendren, R; Siriwardena, K; Phillips, J; Sanchez-Valle, A; Waisbren, S; Gillis, J; Prasad, S; Merilainen, M; Lang, W; Zhang, C; Yu, S; Stahl, S

    2015-03-01

    Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced. PMID:25533024

  19. PKU and Maternal PKU: The Cure and the Problem.

    ERIC Educational Resources Information Center

    Henderson, Robert A.

    1989-01-01

    A longitudinal study is evaluating the efficacy of a phenylalanine-restricted diet in reducing disabling conditions associated with maternal hyperphenylalaninemia. Titled the Maternal PKU Collaborative Study, it is studying 162 American and Canadian women and involves diet therapy, prenatal examinations, laboratory tests, nutritional evaluation,…

  20. Predicting a clinical/biochemical phenotype for PKU/MHP patients with PAH gene mutations.

    PubMed

    Kasnauskiene, J; Cimbalistiene, L; Kucinskas, V

    2008-10-01

    Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). In this study, a total of 218 independent PAH chromosomes (109 unrelated patients with PKU residing in Lithuania) were investigated. All 13 exons of the PAH gene of all PKU probands were scanned for DNA alterations by denaturing gradient gel electrophoresis (DGGE). In the cases of a specific DGGE pattern recognised, mutations were identified by direct fluorescent automated sequencing or by restriction enzyme digestion analysis of a relevant exons. 25 different PAH gene mutations were identified in Lithuania. We estimated a connection between individual PAH locus mutations and biochemical and metabolic phenotypes in patients in whom the mutant allele acts on its own, i.e., in functionally hemizygous patients and using the assigned value (AV) method to determine the severity of both common and rare mutant alleles, as well as to check a model to predict the combined phenotypic effect of two mutant PAH alleles. PMID:19062537

  1. Utility of phenylalanine hydroxylase genotype for tetrahydrobiopterin responsiveness classification in patients with phenylketonuria

    PubMed Central

    Quirk, Meghan E.; Dobrowolski, Steven F.; Nelson, Benjamin E.; Coffee, Bradford; Singh, Rani H.

    2014-01-01

    Background A need exists to expand the characterization of tetrahydrobiopterin (BH4) responsiveness in patients with phenylketonuria (PKU), beyond simply evaluating change in blood phenylalanine concentrations. The clinical interpretation of BH4 responsiveness should be evaluated within the context of phenylalanine hydroxylase (PAH) genotype. Aim This investigation seeks to use a modified version of a previously developed PAH genotype severity tool, the assigned value (AV) sum, to assess the molecular basis of responsiveness in a clinical cohort and to explore the tool’s ability to differentiate BH4 responsive groups. Methods BH4 response was previously clinically classified in 58 patients with PKU, with three response groups emerging: definitive responders, provisional responders, and non-responders. Provisional responders represented a clinically ambiguous group, with an initial decrease in plasma phenylalanine concentrations, but limited ability to improve dietary phenylalanine tolerance. In this retrospective analysis, mutations in the PAH gene were identified in each patient. PAH genotype was characterized through the AV sum approach, in which each mutation is given an AV of 1, 2, 4, or 8; the sum of both mutations’ AV corresponds to genotype severity, with a lower number representing a more severe phenotype. An AV sum cutoff of 2 (indicative of the most severe genotypes) was used to dichotomize patients and predict BH4 responsiveness. Provisional responders were classified with the definitive responders then the non-responders to see with which group they best aligned. Results In 17/19 definitive responders, at least one mutation was mild or moderate in severity (AV sum>2). In contrast, 7/9 provisional responders carried two severe or null mutations (AV sum=2), suggesting little molecular basis for responsiveness. Non-responders represent a heterogeneous group with 15/25 patients carrying two severe mutations (AV sum=2), 5/25 patients carrying one

  2. Variability in phenylalanine control predicts IQ and executive abilities in children with phenylketonuria.

    PubMed

    Hood, Anna; Grange, Dorothy K; Christ, Shawn E; Steiner, Robert; White, Desirée A

    2014-04-01

    A number of studies have revealed significant relationships between cognitive performance and average phenylalanine (Phe) levels in children with phenylketonuria (PKU), but only a few studies have been conducted to examine the relationships between cognitive performance and variability (fluctuations) in Phe levels. In the current study, we examined a variety of indices of Phe control to determine which index best predicted IQ and executive abilities in 47 school-age children with early- and continuously-treated PKU. Indices of Phe control were mean Phe, the index of dietary control, change in Phe with age, and several indices of variability in Phe (standard deviation, standard error of estimate, and percentage of spikes). These indices were computed over the lifetime and during 3 developmental epochs (<5, 5.0-9.9, and ≥10 years of age). Results indicated that variability in Phe was generally a stronger predictor of cognitive performance than other indices of Phe control. In addition, executive performance was better predicted by variability in Phe during older than younger developmental epochs. These results indicate that variability in Phe should be carefully controlled to maximize cognitive outcomes and that Phe control should not be liberalized as children with PKU age. PMID:24568837

  3. Variability in Phenylalanine Control Predicts IQ and Executive Abilities in Children with Phenylketonuria

    PubMed Central

    Hood, Anna; Grange, Dorothy K.; Christ, Shawn E.; Steiner, Robert; White, Desirée A.

    2014-01-01

    A number of studies have revealed significant relationships between cognitive performance and average phenylalanine (Phe) levels in children with phenylketonuria (PKU), but only a few studies have been conducted to examine relationships between cognitive performance and variability (fluctuations) in Phe levels. In the current study, we examined a variety of indices of Phe control to determine which index best predicted IQ and executive abilities in 47 school-age children with early- and continuously-treated PKU. Indices of Phe control were mean Phe, the index of dietary control, change in Phe with age, and several indices of variability in Phe (standard deviation, standard error of estimate, and percentage of spikes). These indices were computed over the lifetime and during 3 developmental epochs (< 5, 5.0 – 9.9, and ≥ 10 yrs. of age). Results indicated that variability in Phe was generally a stronger predictor of cognitive performance than other indices of Phe control. In addition, executive performance was better predicted by variability in Phe during older than younger developmental epochs. These results indicate that variability in Phe should be carefully controlled to maximize cognitive outcomes, and that Phe control should not be liberalized as children with PKU age. PMID:24568837

  4. Nutrition studies in treated infants and children with phenylketonuria: vitamins, minerals, trace elements.

    PubMed

    Acosta, P B

    1996-07-01

    Chemically defined or elemental medical foods provide the majority of protein equivalent in the diets of children treated for phenylketonuria (PKU). Because of the restricted intake of high biologic value protein, children with PKU often have lower than normal plasma concentrations of ferritin and zinc. Few reported studies are available on vitamin status of children with PKU undergoing treatment. This report addresses intakes of iron, zinc and vitamin A and their plasma concentrations in children ingesting either a low phenyl-alanine (Phe) casein hydrolysate or a Phe-free L-amino acid mix. With significantly greater than recommended mean intakes of iron and low to recommended mean intakes of zinc, individual plasma ferritin concentrations were often in the deficient (< 12 ng/ml) or marginal (12 < 20 ng/ml) range; plasma zinc concentrations were usually normal when patients received an L-amino acid mix. When L-amino acids were the source of protein equivalent for infants, 48% of plasma retinol concentrations were in the marginal (20 < 30 micrograms/dl) or deficient range (< 20 micrograms/dl) in spite of most vitamin A intakes being greater than Recommended Dietary Allowance for age. Some hypothetical reasons for low concentrations of plasma ferritin and retinol are discussed. PMID:8828630

  5. Erythrocyte-mediated delivery of phenylalanine ammonia lyase for the treatment of phenylketonuria in BTBR-Pah(enu2) mice.

    PubMed

    Rossi, Luigia; Pierigè, Francesca; Carducci, Claudia; Gabucci, Claudia; Pascucci, Tiziana; Canonico, Barbara; Bell, Sean M; Fitzpatrick, Paul A; Leuzzi, Vincenzo; Magnani, Mauro

    2014-11-28

    Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by defects in the phenylalanine hydroxylase gene. Preclinical and clinical investigations suggest that phenylalanine ammonia lyase (PAL) could be an effective alternative for the treatment of PKU. The aim of this study is to investigate if erythrocytes loaded with PAL may act as a safe delivery system able to overcome bioavailability issues and to provide, in vivo, a therapeutically relevant concentration of enzyme. Murine erythrocytes were loaded with recombinant PAL from Anabaena variabilis (rAvPAL) and their ability to perform as bioreactors was assessed in vivo in adult BTBR-Pah(enu2) mice, the genetic murine model of PKU. Three groups of mice were treated with a single i.v. injection of rAvPAL-RBCs at three different doses to select the most appropriate one for assessment of efficacy. Repeated administrations at 9-10 day-intervals of the selected dose for 10 weeks showed that the therapeutic effect was persistent and not affected by the generation of antibodies induced by the recombinant enzyme. This therapeutic approach deserves further in vivo evaluation either as a potential option for the treatment of PKU patients or as a possible model for the substitutive enzymatic treatment of other inherited metabolic disorders. PMID:25151978

  6. What Is the Diet for PKU?

    MedlinePlus

    ... range helps to prevent problems with thinking and problem solving. In the past, people with PKU were advised to stop their low phe diet when they were children. Most young people with PKU ... with paying attention, concentrating, and remembering. Recently, many ...

  7. Phenylalanine hydroxylase gene mutations in the United States: report from the Maternal PKU Collaborative Study.

    PubMed Central

    Guldberg, P.; Levy, H. L.; Hanley, W. B.; Koch, R.; Matalon, R.; Rouse, B. M.; Trefz, F.; de la Cruz, F.; Henriksen, K. F.; Güttler, F.

    1996-01-01

    The major cause of hyperphenylalaninemia is mutations in the gene encoding phenylalanine hydroxylase (PAH). The known mutations have been identified primarily in European patients. The purpose of this study was to determine the spectrum of mutations responsible for PAH deficiency in the United States. One hundred forty-nine patients enrolled in the Maternal PKU Collaborative Study were subjects for clinical and molecular investigations. PAH gene mutations associated with phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) were identified on 279 of 294 independent mutant chromosomes, a diagnostic efficiency of 95%. The spectrum is composed of 71 different mutations, including 47 missense mutations, 11 splice mutations, 5 nonsense mutations, and 8 microdeletions. Sixteen previously unreported mutations were identified. Among the novel mutations, five were found in patients with MHP, and the remainder were found in patients with PKU. The most common mutations were R408W, IVS12nt1g-->a, and Y414C, accounting for 18.7%, 7.8%, and 5.4% of the mutant chromosomes, respectively. Thirteen mutations had relative frequencies of 1%-5%, and 55 mutations each had frequencies < or = 1%. The mutational spectrum corresponded to that observed for the European ancestry of the U.S. population. To evaluate the extent of allelic variation at the PAH locus within the United States in comparison with other populations, we used allele frequencies to calculate the homozygosity for 11 populations where >90% ascertainment of mutations has been obtained. The United States was shown to contain one of the most heterogeneous populations, with homozygosity values similar to Sicily and ethnically mixed sample populations in Europe. The extent of allelic heterogeneity must be a major determining factor in the choice of mutation-detection methodology for molecular diagnosis in PAH deficiency. Images Figure 1 PMID:8659548

  8. A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement.

    PubMed

    Guldberg, P; Zschocke, J; Dagbjartsson, A; Henriksen, K F; Güttler, F

    1997-01-01

    Iceland was settled during the late 9th and early 10th centuries AD by Vikings who arrived from Norway and the British Isles. Although it is generally acknowledged that the Vikings brought with them Celtic slaves, the relative contribution of these peoples to the modern Icelandic gene pool has been a matter of considerable discussion. Most population genetic studies using classical markers have indicated a large Irish genetic contribution. We have investigated the molecular basis of phenylketonuria (PKU) in 17 Icelandic patients and found 9 different mutations in the phenylalanine hydroxylase gene. One novel mutation, Y377fsdelT, accounts for more than 40% of the mutant chromosomes. Haplotype data support a common ancestral origin of the mutation, and genealogical examination extending back more than 5 generations shows that this mutation has probably arisen in an isolated part of southern Iceland and was enriched by a founder effect. At least 7 PKU mutations have originated outside iceland. The almost exclusively Scandinavian background of these mutations and the complete absence of common Irish PKU mutations strongly support historical and linguistic evidence of a predominant Scandinavian heritage of the Icelandic people. PMID:9450182

  9. Time and space clusters of the French-Canadian MIV phenylketonuria mutation in France

    PubMed Central

    Lyonnet, Stanislas; Melle, Dominique; de Braekeleer, Marc; Laframboise, Rachel; Rey, Françoise; John, Simon W. M.; Berthelon, Monique; Berthelot, Jacques; Journel, Hubert; Le Marec, Bernard; Parent, Philippe; de Parscau, Loïc; Saudubray, Jean-Marie; Rozen, Rima; Rey, Jean; Munnich, Arnold; Scriver, Charles R.

    1992-01-01

    We performed mutation analysis and RFLP haplotype analysis of chromosomes associated with classical phenylketonuria (PKU) in contemporary French families. We also did genealogical reconstructions for seven obligate carriers in five contemporary French-Canadian families living in eastern Quebec, who carry the M1V mutation causing PKU. The M1V mutation, heretofore considered to be associated exclusively with French-Canadians, was found on 4 of 152 independent French chromosomes. The French and Quebec M1V mutations all occurred on RFLP haplotype 2. The contemporary mutant French chromosomes clustered in southern Brittany (Finistère Sud). Genealogical reconstructions of the Quebec families identified 53 shared ancestors and a center of diffusion in the Perche region in 17th century France. The two clusters in France, one historical and the other contemporary, are not incompatible, if one assumes the possibilities that settlers returned from Nouvelle France or moved from Perche to southern Brittany. The M1V mutation is serving as a useful marker for historical demography. ImagesFigure 1Figure 3 PMID:1609797

  10. Reassessment of Phenylalanine Tolerance in Adults with Phenylketonuria is Needed as Body Mass Changes

    PubMed Central

    MacLeod, Erin L.; Gleason, Sally T.; van Calcar, Sandra C.; Ney, Denise M.

    2009-01-01

    Lifelong treatment of phenylketonuria (PKU) includes a phenylalanine (phe) restricted diet that provides sufficient phe for growth and maintenance plus phe-free amino acid formula to meet requirements for protein, energy and micronutrients. Phe tolerance (mg phe/kg body weight/day) is the amount of phe those with PKU can consume and maintain acceptable blood phe levels; it requires individual assessment because of varying phenylalanine hydroxylase activity. The objective was to reassess phe tolerance in 8 adults with PKU considering phe requirements, blood phe levels, genotype and phe tolerance at 5 years of age. Subjects had not received a personalized assessment of phe tolerance in several years, and 5 subjects were overweight, body mass index (BMI) 25–28. With the guidance of a metabolic dietitian, 7 subjects increased phe tolerance (by 15–173%) without significantly increasing blood phe concentration. Increased phe tolerance was associated with both improved dietary compliance and inadequate phe intake at the onset of the protocol compared with current requirements. Improved dietary compliance reflected increased consumption of protein equivalents from amino acid formula and increased frequency of formula intake, from 2.2 to 3 times per day. Predictors of higher final phe tolerance following reassessment included being male and having a lower BMI (R2=0.588). This suggests that the rising trend of overweight and obesity may affect assessment of phe tolerance in adults. Therefore, interaction with the metabolic dietitian to reassess phe tolerance in relation to body mass is essential throughout adulthood to insure adequate intake of phe to support protein synthesis and prevent catabolism. PMID:19747868

  11. Mutations of the phenylalanine hydroxylase gene in Iranian patients with phenylketonuria.

    PubMed

    Biglari, Alireza; Saffari, Fatemeh; Rashvand, Zahra; Alizadeh, Safarali; Najafipour, Reza; Sahmani, Mehdi

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene. The aim of this study was the identification of sixteen different mutations in Iranian patients with hyperphenylalaninemia. The mutations were detected during the characterization of PAH genotypes of 39 PKU patients from Qazvin and Zanjan provinces of Iran. PAH mutations have been analyzed by PCR and direct sequencing of PCR products of the promoter region and all 13 exons of PAH gene, including the splicing sites. A mutation detection rate of 74.3 % was realized. Two mutations were found at high frequencies: R176X (10.25 %) and p.P281L (10.25 %). The frequencies of the other mutations were: IVS2+5G>A (2.56 %), IVS2+5G>C (2.56 %), p.L48S (2.56 %), p.R243Q (2.56 %), p.R252Q (5.12 %), p.R261Q (7.69 %), p.R261X (5.12 %), p.E280K (2.56 %), p.I283N (2.56 %), IVS9+5G>A (2.56 %), IVS9+1G>A (1.28 %), IVS11+1G>C (1.28 %), p.C357R (1.28 %), c.632delC (2.56 %). The present results confirm the high heterogeneity of the PAH locus and contribute to information about the distribution and frequency of PKU mutations in the Iranian population. PMID:26413448

  12. Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes.

    PubMed

    MacLeod, Erin L; Gleason, Sally T; van Calcar, Sandra C; Ney, Denise M

    2009-12-01

    Lifelong treatment of phenylketonuria (PKU) includes a phenylalanine (phe) restricted diet that provides sufficient phe for growth and maintenance plus phe-free amino acid formula to meet requirements for protein, energy and micronutrients. Phe tolerance (mg phe/kg body weight/day) is the amount of phe those with PKU can consume and maintain acceptable blood phe levels; it requires individual assessment because of varying phenylalanine hydroxylase activity. The objective was to reassess phe tolerance in eight adults with PKU considering phe requirements, blood phe levels, genotype and phe tolerance at 5 years of age. Subjects had not received a personalized assessment of phe tolerance in several years, and five subjects were overweight, body mass index (BMI) 25-28. With the guidance of a metabolic dietitian, seven subjects increased phe tolerance (by 15-173%) without significantly increasing blood phe concentration. Increased phe tolerance was associated with both improved dietary compliance and inadequate phe intake at the onset of the protocol compared with current requirements. Improved dietary compliance reflected increased consumption of protein equivalents from amino acid formula and increased frequency of formula intake, from 2.2 to 3 times per day. Predictors of higher final phe tolerance following reassessment included being male and having a lower BMI (R(2)=0.588). This suggests that the rising trend of overweight and obesity may affect assessment of phe tolerance in adults. Therefore, interaction with the metabolic dietitian to reassess phe tolerance in relation to body mass is essential throughout adulthood to insure adequate intake of phe to support protein synthesis and prevent catabolism. PMID:19747868

  13. Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria.

    PubMed

    Lee, Phillip; Treacy, Eileen P; Crombez, Eric; Wasserstein, Melissa; Waber, Lewis; Wolff, Jon; Wendel, Udo; Dorenbaum, Alex; Bebchuk, Judith; Christ-Schmidt, Heidi; Seashore, Margretta; Giovannini, Marcello; Burton, Barbara K; Morris, Andrew A

    2008-11-15

    Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation, which can lead to neurocognitive and neuromotor impairment. Sapropterin dihydrochloride, an FDA-approved synthetic formulation of tetrahydrobiopterin (6R-BH4, herein referred to as sapropterin) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)-responsive PKU, offering potential for improved metabolic control. Eighty patients, > or =8 years old, who had participated in a 6-week, randomized, placebo-controlled study of sapropterin, were enrolled in this 22-week, multicenter, open-label extension study comprising a 6-week forced dose-titration phase (5, 20, and 10 mg/kg/day of study drug consecutively for 2 weeks each), a 4-week dose-analysis phase (10 mg/kg/day), and a 12-week fixed-dose phase (patients received doses of 5, 10, or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration). Dose-dependent reductions in plasma Phe concentrations were observed in the forced dose-titration phase. Mean (SD) plasma Phe concentration decreased from 844.0 (398.0) micromol/L (week 0) to 645.2 (393.4) micromol/L (week 10); the mean was maintained at this level during the study's final 12 weeks (652.2 [382.5] micromol/L at week 22). Sixty-eight (85%) patients had at least one adverse event (AE). All AEs, except one, were mild or moderate in severity. Neither the severe AE nor any of the three serious AEs was considered related to sapropterin. No AE led to treatment discontinuation. Sapropterin is effective in reducing plasma Phe concentrations in a dose-dependent manner and is well tolerated at doses of 5-20 mg/kg/day over 22 weeks in BH4-responsive patients with PKU. PMID:18932221

  14. The Electro-Encephalogram in Phenylketonuria

    ERIC Educational Resources Information Center

    Todd, Peter G.; Pitt, D. B.

    1973-01-01

    Evaluated were electroencephalographic findings in 24 untreated (ages from 4 to 38 years) patients suffereing from phenylketonuria (a metabolic disorder producing severe mental retardation if not treated with proper diet during the early years). (DB)

  15. Child and Parent Attributions in Chronic Pediatric Conditions: Phenylketonuria (PKU) as an Exemplar

    ERIC Educational Resources Information Center

    Antshel, Kevin M.; Brewster, Scott; Waisbren, Susan E.

    2004-01-01

    Background: Attribution theory, self-regulation, self-handicapping and sick role theories all suggest that children with chronic disease may be held to different standards. This study assesses child and parent attributions in pediatric chronic health conditions and addresses how attributional style may be related to treatment adherence. Methods:…

  16. Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters

    PubMed Central

    Yano, Shoji; Moseley, Kathryn; Fu, Xiaowei; Azen, Colleen

    2016-01-01

    Background Phenylketonuria (PKU) is due to a defective hepatic enzyme, phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU. Objective (1) To evaluate the effects of sapropterin (BH4) and concurrent use of large neutral amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2) To evaluate synergistic effects with BH4 and LNAA. (3) To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations. Methods Nine adults with PKU completed our study consisting of four 4-week phases: (1) LNAA supplementation, (2) Washout, (3) BH4 therapy, and (4) LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase. Results (1) Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2) Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3) The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005) with a trend toward differing slopes among individual subjects (p = 0.066). There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047). Conclusion Blood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring

  17. Phenylketonuria

    MedlinePlus

    ... without the ability to properly break down an amino acid called phenylalanine. ... which is needed to break down the essential amino acid phenylalanine. Phenylalanine is found in foods that contain ...

  18. Complete correction of hyperphenylalaninemia following liver-directed, recombinant AAV2/8 vector-mediated gene therapy in murine phenylketonuria

    PubMed Central

    Harding, CO; Gillingham, MB; Hamman, K; Clark, H; Goebel-Daghighi, E; Bird, A; Koeberl, DD

    2009-01-01

    Novel recombinant adeno-associated virus vectors pseudo-typed with serotype 8 capsid (rAAV2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. We have produced a novel liver-specific rAAV2/8 vector expressing the mouse phenylalanine hydroxylase (Pah) cDNA and have administered this vector to hyperphenylalaninemic PAH-deficient Pahenu2 mice, a model of human phenylketonuria (PKU). Our hypothesis was that this vector would produce sufficient hepatocyte transduction frequency and PAH activity to correct blood phenylalanine levels in murine PKU. Portal vein injection of recombinant AAV2/8 vector into five adult Pahenu2 mice yielded complete and stable (up to 17 weeks) correction of serum phenylalanine levels. Liver PAH activity was corrected to 11.5±2.4% of wild type liver activity and was associated with a significant increase in phenylalanine clearance following parenteral phenylalanine challenge. Although questions of long-term safety and stability of expression remain, recombinant AAV2/8-mediated, liver-directed gene therapy is a promising novel treatment approach for PKU and allied inborn errors of metabolism. PMID:16319949

  19. Complete correction of hyperphenylalaninemia following liver-directed, recombinant AAV2/8 vector-mediated gene therapy in murine phenylketonuria.

    PubMed

    Harding, C O; Gillingham, M B; Hamman, K; Clark, H; Goebel-Daghighi, E; Bird, A; Koeberl, D D

    2006-03-01

    Novel recombinant adeno-associated virus vectors pseudotyped with serotype 8 capsid (rAAV2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. We have produced a novel liver-specific rAAV2/8 vector expressing the mouse phenylalanine hydroxylase (Pah) cDNA and have administered this vector to hyperphenylalaninemic PAH-deficient Pah(enu2) mice, a model of human phenylketonuria (PKU). Our hypothesis was that this vector would produce sufficient hepatocyte transduction frequency and PAH activity to correct blood phenylalanine levels in murine PKU. Portal vein injection of recombinant AAV2/8 vector into five adult Pah(enu2) mice yielded complete and stable (up to 17 weeks) correction of serum phenylalanine levels. Liver PAH activity was corrected to 11.5+/-2.4% of wild type liver activity and was associated with a significant increase in phenylalanine clearance following parenteral phenylalanine challenge. Although questions of long-term safety and stability of expression remain, recombinant AAV2/8-mediated, liver-directed gene therapy is a promising novel treatment approach for PKU and allied inborn errors of metabolism. PMID:16319949

  20. In vitro read-through of phenylalanine hydroxylase (PAH) nonsense mutations using aminoglycosides: a potential therapy for phenylketonuria.

    PubMed

    Ho, Gladys; Reichardt, Juergen; Christodoulou, John

    2013-11-01

    Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of phenylalanine metabolism, predominantly caused by mutations in the phenylalanine hydroxylase (PAH) gene. Approximately 10% of patients carry a nonsense mutation, which results in an inactive or unstable truncated protein. In some genetic disorders, including cystic fibrosis and Duchenne muscular dystrophy, restoration of full-length protein has been achieved by aminoglycoside antibiotics, such as gentamicin and G-418 (Geneticin). More recently, nonsense read-through has been induced at greater rates using a non-aminoglycoside drug, PTC124 (Ataluren), which has the advantage of being non-toxic in contrast to the antibiotics. The efficacy of read-through induced by three compounds, aminoglycosides G418 and gentamicin, and PTC124 were evaluated for four nonsense mutations of PAH in an in vitro expression system in two mammalian cell lines (COS-7 and HEK293). The production of full-length PAH was investigated using western blotting and the functionality confirmed by enzyme activity. Gentamicin and G-418 induced read-through of nonsense PAH mutations in HEK293 cells. The read-through product partially restored enzymatic activity, which was significantly less than that of wild-type, but comparable to a missense mutation of PAH associated with less severe forms of PKU. Treatment with PTC124 up to 100 μM did not result in full-length PAH polypeptide. Nonsense read-through drugs are a potential form of treatment for PKU, although the high dosage of aminoglycosides used is not appropriate in a clinical setting. In vitro studies with new non-toxic read-through agents as well as in vivo studies would also be essential to determine the extent of read-through required to restore normal phenylalanine levels. PMID:23532445

  1. Reinstitution of diet therapy in PKU patients from twenty-two US clinics.

    PubMed

    Schuett, V E; Brown, E S; Michals, K

    1985-01-01

    In a nationwide survey we found 72 PKU (phenylketonuria) patients who had terminated diet but later returned to diet. Sixty-one patients resumed diet due to clinical problems. Age at initial diet discontinuation ranged from three to 20 years. The most prevalent problems reported were poor school performance, and mood and/or behavior changes. Following diet reinstitution, only positive changes were noted for 42 patients, no changes for 19 patients, and 11 had one or more negative changes. Improvements and blood phenylalanine levels were not significantly correlated, but only 11 patients maintained levels less than 10 mg/dl. The number of improvements was significantly correlated with length of time on diet (p less than 0.001). After a median of 10 months on diet, 22 patients had again discontinued due to poor diet control, lack of motivation, poor formula tolerance, lack of apparent benefits and/or changes for the worse. Median time on diet for the 50 second-time continuers was two years nine months. PMID:3966596

  2. Molecular screening of genetic defects with RNA-SSCP analysis: the PKU and cystinuria model.

    PubMed

    Giannattasio, S; Bisceglia, L; Lattanzio, P; Grifa, A; Dianzani, I; Gasparini, P; Marra, E

    1995-06-01

    RNA single-strand conformation polymorphism (rSSCP) is a recently developed method for detecting genetic defects. This technique requires DNA amplification with a polymerase chain reaction making use of one T7 promoter-containing primer. Amplification products are subsequently transcribed in vitro and the labelled transcripts are analysed for single-strand conformation changes. rSSCP has been applied to mutation screening of the phenylalanine hydroxylase gene and rBAT cDNA, from PKU and cystinuric patients, respectively. Experimental evidence shows that 83% and 86% of screened PKU and cystinuric mutations, respectively, give rise to detectable rSSCP signals. Thus, results obtained show that RNA single-strand conformation polymorphism analysis is generally applicable and is a suitable technique for detecting genetic disease causing mutations, both in basic research and in clinical practice. PMID:7477014

  3. Study on urinary metabolic profile of phenylketonuria by micellar electrokinetic capillary chromatography with dual electrochemical detection--potential clinical application in fast diagnosis of phenylketonuria.

    PubMed

    Zhang, Dongli; Li, Wenli; Zhang, Junbo; Tang, Wanrong; Qian, Chenxu; Feng, Minghao; Chu, Qingcui; Ye, Jiannong

    2011-05-23

    The urinary metabolic marker compounds, namely phenylpyruvic acid (PPA), 2-hydroxyphenylacetic acid (oOPAA), 4-hydroxyphenylacetic acid (pOPAA), phenyllactic acid (PLA) and phenylacetic acid (PAA) of phenylketonuric individuals were detected by a novel method of micellar electrokinetic capillary chromatography with capacitively coupled contactless conductivity detection and amperometric detection (MECC-C(4)D/AD). Electrophoretic runs were performed in a 35 mmol L(-1) SDS/60 mmol L(-1) H(3)BO(3)-Na(2)B(4)O(7) running buffer (pH 8.2) at a separation voltage of 16 kV, and five marker compounds and the major coexisting compound uric acid (UA) could be well separated within 23 min. Highly linear response was obtained for five marker compounds over three orders of magnitude with detection limits ranging from 6.6×10(-6) to 6.4×10(-8) g mL(-1) (S/N=3). The proposed method has been used to detect the marker compounds simultaneously in urine samples with the advantages of obtaining more information about target analytes and avoiding redundant measurements and high assay cost. Urinary patterns in phenylketonuric babies were distinct and easily distinguished from those of healthy newborns. The proposed MECC-C(4)D/AD method could find clinical application in early noninvasive diagnosis of phenylketonuria (PKU), as significant differences could be found in the urinary content of five marker compounds among the phenylketonuric babies without or with dietotherapy and the healthy babies. PMID:21565303

  4. Diurnal variation of phenylalanine and tyrosine concentrations in adult patients with phenylketonuria: subcutaneous microdialysis is no adequate tool for the determination of amino acid concentrations

    PubMed Central

    2013-01-01

    Background Metabolic control and dietary management of patients with phenylketonuria (PKU) are based on single blood samples obtained at variable intervals. Sampling conditions are often not well-specified and intermittent variation of phenylalanine concentrations between two measurements remains unknown. We determined phenylalanine and tyrosine concentrations in blood over 24 hours. Additionally, the impact of food intake and physical exercise on phenylalanine and tyrosine concentrations was examined. Subcutaneous microdialysis was evaluated as a tool for monitoring phenylalanine and tyrosine concentrations in PKU patients. Methods Phenylalanine and tyrosine concentrations of eight adult patients with PKU were determined at 60 minute intervals in serum, dried blood and subcutaneous microdialysate and additionally every 30 minutes postprandially in subcutaneous microdialysate. During the study period of 24 hours individually tailored meals with defined phenylalanine and tyrosine contents were served at fixed times and 20 min bicycle-ergometry was performed. Results Serum phenylalanine concentrations showed only minor variations while tyrosine concentrations varied significantly more over the 24-hour period. Food intake within the patients’ individual diet had no consistent effect on the mean phenylalanine concentration but the tyrosine concentration increased up to 300% individually. Mean phenylalanine concentration remained stable after short-term bicycle-exercise whereas mean tyrosine concentration declined significantly. Phenylalanine and tyrosine concentrations in dried blood were significantly lower than serum concentrations. No close correlation has been found between serum and microdialysis fluid for phenylalanine and tyrosine concentrations. Conclusions Slight diurnal variation of phenylalanine concentrations in serum implicates that a single blood sample does reliably reflect the metabolic control in this group of adult patients. Phenylalanine

  5. Mutation analysis of PAH gene in patients with PKU in western Iran and its association with polymorphisms: identification of four novel mutations.

    PubMed

    Alibakhshi, Reza; Moradi, Keyvan; Mohebbi, Zahra; Ghadiri, Keyghobad

    2014-03-01

    Phenylketonuria (PKU) is an autosomal recessive disorder characterized by a mutation in the phenylalanine hydroxylase (PAH) gene. Untreated PKU can lead to mental retardation, seizures, and other serious medical problems. This study was designed to investigate the status of molecular defects in the PAH gene and their association with polymorphisms in Kurdish patients with PKU in the Kermanshah province, western Iran. The study was conducted on 27 unrelated patients with PKU over a 2-year period (from 2010 to 2012). All 13 exons plus exon-intron boundaries of the PAH gene were analyzed and we identified 15 different mutations, including two novel mutations, in 51 of the 54 mutant alleles (diagnostic efficiency of 94.4 %). IVS4 + 1G > C (c.441 + 1G > C) and IVS7 - 5 T > C (c.843 - 5 T > C) are novel mutations that have not been reported in the academic literature or the PAH locus database ( http://www.pahdb.mcgill.ca ); therefore, they may be specific to the Kurdish population. IVS2 + 5G > C and IVS9 + 5G > A were the two most prevalent mutations in our sample, with frequencies of 26 % and 17 %, respectively. The second most common mutations were p.R261X, IVS10 - 11G > A, p.K363 > Nfs and IVS7 - 5 T > C, with each showing a relative frequency of 7.4 %. All other detected mutations, including p.F55 > Lfs, p.R176X, p.R243Q, p.V230I, p.R243X, p.R261Q, IVS8 - 7A > G and p.E390G had frequencies of less than 4 %. The present study showed that there is a distinct difference in the characteristics of PAH mutations between the Kermanshah province and other parts of Iran, suggesting that Kermanshah may have a unique population distribution of PAH gene mutations. Iran lies on the route of major ancient movements of the Caucasian people toward the Mediterranean basin, and Kermanshah has previously been called the gateway to Asia. Most of the mutations identified in this study are common in the Mediterranean region. Therefore, our findings are consistent with the historical and

  6. Psychosocial factors in maternal phenylketonuria: women's adherence to medical recommendations.

    PubMed Central

    Waisbren, S E; Hamilton, B D; St James, P J; Shiloh, S; Levy, H L

    1995-01-01

    OBJECTIVES. This study identified factors predicting adherence to medical recommendations in maternal phenylketonuria, which can result in severe fetal damage. METHODS. Sixty-nine women with phenylketonuria, 68 of their acquaintances, and 69 women with diabetes mellitus were interviewed annually for 5 years. A model in which each stage in the maternal phenylketonuria life cycle represented a treatment-related goal provided a means to assess adherence. RESULTS. At the stages of prevention of unplanned pregnancy, treatment initiation, and diet continuation throughout pregnancy, attitudes and social support were associated with adherence to medical recommendations. No specific variables were associated with outcome at reproductive decision making, but women with phenylketonuria were more likely to delay making a decision, resulting in unplanned and, hence, untreated or late-treated pregnancy. CONCLUSIONS. Women with phenylketonuria differed from their acquaintances and diabetic women in many respects, suggesting that special programs are needed. Greater emphasis on reproductive decision making is especially needed. Interventions that focus on improving social support networks and attitudes about treatment may increase adherence to recommendations. PMID:7503337

  7. Clinical relevance of the discrepancy in phenylalanine concentrations analyzed using tandem mass spectrometry compared with ion-exchange chromatography in phenylketonuria

    PubMed Central

    Stroup, Bridget M.; Held, Patrice K.; Williams, Phillip; Clayton, Murray K.; Murali, Sangita G.; Rice, Gregory M.; Ney, Denise M.

    2016-01-01

    Introduction Metabolic control of phenylketonuria (PKU) and compliance with the low-phenylalanine (phe) diet are frequently assessed by measuring blood phe concentrations in dried blood spots (DBS) collected by patients instead of plasma phe concentrations. Objective Our objective was to investigate the difference in blood phe concentrations in DBS collected by subjects and analyzed using either a validated newborn screening tandem mass spectrometry (MS/MS) protocol or ion-exchange chromatography (IEC) compared to plasma phe concentrations obtained simultaneously and analyzed using IEC. Design Three to four fasting blood samples were obtained from 29 subjects with PKU, ages 15–49 years. Capillary blood was spotted on filter paper by each subject and the DBS analyzed using both MS/MS and IEC. Plasma was isolated from venous blood and analyzed using IEC. Results Blood phe concentrations in DBS analyzed using MS/MS are 28% ± 1% (n = 110, p < 0.0001) lower than plasma phe concentrations analyzed using IEC resulting in a blood phe concentration of 514 ± 23 μmol/L and a plasma phe concentration of 731 ± 32 μmol/L (mean ± SEM). This discrepancy is larger when plasma phe is > 600 μmol/L. Due to the large variability across subjects of 13.2%, a calibration factor to adjust blood phe concentrations is not recommended. Analysis of DBS using IEC reduced the discrepancy to 15 ± 2% lower phe concentrations compared to plasma analyzed using IEC (n = 38, p = 0.0001). This suggests that a major contributor to the discrepancy in phe concentrations is the analytical method. Conclusion Use of DBS analyzed using MS/MS to monitor blood phe concentrations in individuals with PKU yields significantly lower phe levels compared to plasma phe levels analyzed using IEC. Optimization of current testing methodologies for measuring phe in DBS, along with patient education regarding the appropriate technique for spotting blood on filter paper is needed to improve

  8. Intense beams from gases generated by a permanent magnet ECR ion source at PKU.

    PubMed

    Ren, H T; Peng, S X; Lu, P N; Yan, S; Zhou, Q F; Zhao, J; Yuan, Z X; Guo, Z Y; Chen, J E

    2012-02-01

    An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about 120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and 65 mA of He(+) extracted at 50 kV through a φ 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 π mm mrad. Tungsten samples were irradiated by H(+) or He(+) beam extracted from this ion source and H∕He holes and bubbles have been observed on the samples. A method to produce a high intensity H∕He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He(+) beam injector for coupled radio frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He(+) beam. PMID:22380337

  9. Collaborative Study of Children Treated for Phenylketonuria: Study Design

    ERIC Educational Resources Information Center

    Williamson, Malcolm; And Others

    1977-01-01

    Available from: Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. Described is a study in which a large sample of children (n=444) with phenylketonuria (an inborn metabolic error usually related to impaired cognitive ability) were treated under controlled conditions from near birth to 6 years of age.…

  10. PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

    ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

  11. A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: A pilot study☆, ☆☆

    PubMed Central

    Yi, S.H.L.; Kable, J.A.; Evatt, M.L.; Singh, R.H.

    2014-01-01

    Low blood docosahexaenoic acid (DHA) is reported in patients with phenylketonuria (PKU); however, the functional implications in adolescents and adults are unknown. This pilot study investigated the effect of supplemental DHA on cognitive performance in 33 females with PKU ages 12–47 years. Participants were randomly assigned to receive DHA (10 mg/kg/day) or placebo for 4.5 months. Performance on cognitive processing speed and executive functioning tasks was evaluated at baseline and follow up. Intention-to-treat and per protocol analyses were performed. At follow up, biomarkers of DHA status were significantly higher in the DHA-supplemented group. Performance on the cognitive tasks and reported treatment-related adverse events did not differ. While no evidence of cognitive effect was seen, a larger sample size is needed to be conclusive, which may not be feasible in this population. Supplementation was a safe and effective way to increase biomarkers of DHA status (www.clinicaltrials.gov; Identifier: NCT00892554). PMID:22000478

  12. Incidence of phenylketonuria in British Columbia, 1950-1971

    PubMed Central

    Lowry, R. B.; Tischler, B.; Cockcroft, W. H.; Renwick, D. H. G.

    1972-01-01

    The incidence of PKU in British Columbia in the 1950-1971 period is 1/18,750 which corresponds to that found in two other Canadian studies.2, 3 Evidence is presented which shows a trend toward a decline in incidence; however, this is not statistically significant. There is a preponderance of male cases in all age groups. PMID:5035136

  13. PKU in Minas Gerais State, Brazil: mutation analysis.

    PubMed

    Santos, L L; Castro-Magalhães, M; Fonseca, C G; Starling, A L P; Januário, J N; Aguiar, M J B; Carvalho, M R S

    2008-11-01

    This work was undertaken in order to ascertain the PKU mutational spectrum in Minas Gerais, Brazil, the relative frequency of the mutations in the State and the origin of these mutations by haplotype determination. Minas Gerais is a trihybrid population formed by miscegenation from Europeans, Africans and Amerindians. All 13 exons of the PAH gene from 78 PKU patients were analyzed, including splicing sites and the promoter region. We identified 30 different mutations and 98% of the PAH alleles were established. A new mutation (Q267X) was identified as well. The most common mutations found were V388M (21.2), R261Q (16.0%), IVS10-11G>A (15.3%), I65T (5.8%), IVS2+5G>C (5.8%), R252W (5.1%), IVS2+5G>A (4.5%), P281L (3.8%) and L348V (3.2%). These nine mutations correspond to 80% of the PKU alleles in the state. Haplotypes were determined to characterize the origin of the PAH alleles. The majority of the mutations found, with respective haplotypes, are frequent in the Iberian Peninsula. However, there were some mutations that are rare in Europe and four previously unreported mutation-haplotype associations. I65T and Q267X were found in association with haplotype 38 and may be African in origin or the result of miscegenation in the Brazilian population. PMID:18798839

  14. Breastfeeding experience in inborn errors of metabolism other than phenylketonuria.

    PubMed

    Huner, G; Baykal, T; Demir, F; Demirkol, M

    2005-01-01

    Breastfeeding has been recommended for the dietary treatment of infants with phenylketonuria, but studies documenting clinical experience in other inborn errors of metabolism are very few. Seven infants diagnosed with methylmalonyl-CoA mutase deficiency (n=2), ornithine carbamoyltransferase deficiency (n=1), propionic acidaemia (n=1), isovaleric acidaemia (n=1), maple syrup urine disease (n=1) and glutaric acidemia type I (n=1) were tried with breastfeeding over two years. After the control of acute metabolic problems, an initial feeding period with a measured volume of expressed breast milk plus a special essential amino acid mixture was continued with breastfeeding on demand and with the addition of a special essential amino acid mixture. Two patients with methylmalonic acidaemia and one patient with glutaric acidaemia type I tolerated breastfeeding on demand very well, with good growth and metabolic control for periods of 18, 8 and 5 months, respectively. In the patient with propionic acidaemia, on-demand breastfeeding continued for 3 months but was terminated after two acute metabolic episodes. The patient with isovaleric acidaemia had insufficiency of breast milk and formula supplementation ended with breast milk cessation. In the patient with severe ornithine carbamoyltransferase deficiency, breastfeeding was stopped owing to poor metabolic control. The patient with maple syrup urine disease also experienced problems, both in metabolic control and in insufficiency of breast milk, resulting in termination of breastfeeding. Breastfeeding of infants with inborn errors of protein catabolism is feasible, but it needs close monitoring with attention to such clinical parameters as growth, development and biochemistry, including amino acids, organic acids and ammonia. PMID:15902548

  15. Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria

    PubMed Central

    De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

    2015-01-01

    A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies. PMID:26510963

  16. Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria.

    PubMed

    De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

    2015-01-01

    A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies. PMID:26510963

  17. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  18. OMEGA-3 LONG-CHAIN POLYUNSATURATED FATTY ACIDS IN OLDER CHILDREN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenylketonuria (PKU), the most prevalent inborn error of metabolism, is usually secondary to low hepatic activity of phenylalanine hydroxylase, the enzyme that catalyzes conversion of phenylalanine to tyrosine. Growth and development of infants and children with PKU who are managed by mandatory n...

  19. Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects.

    PubMed

    Khemir, Sameh; Halayem, Soumeyya; Azzouz, Hatem; Siala, Hajer; Ferchichi, Maherzia; Guedria, Asma; Bedoui, Amel; Abdelhak, Sonia; Messaoud, Taieb; Tebib, Neji; Belhaj, Ahlem; Kaabachi, Naziha

    2016-06-01

    Autism has been reported in untreated patients with phenylketonuria. The authors aimed to explore autism in 15 Tunisian and 4 Algerian phenylketonuria patients, and report their clinical, biochemical and molecular peculiarities. The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised were used for the diagnosis of autism. Five exons of phenylalanine hydroxylase gene (7, 6, 10, 11, and 5) were amplified by polymerase chain reaction and directly sequenced. Among these patients, 15 were suffering from autism at the time of evaluation. Six mutations were identified: p.E280K, p.G352Vfs, IVS10nt11, p.I224T, p.R261Q, and p.R252W. There was no correlation between autism and mutations affecting the phenylalanine hydroxylase gene, but the age of diet onset was the determining factor in autistic symptoms' evolution. PMID:26759449

  20. Treating phenylketonuria by a phenylalanine-free diet.

    PubMed

    Start, K

    1998-01-01

    The phenylalanine-free diet is needed for the treatment of phenylketonuria. Phenylketonuria is an inherited metabolic condition in which there is a deficiency of the enzyme phenylalanine hydroxylase. Lack of this enzyme means the body cannot metabolise the essential amino acid phenylalanine, which then builds up in the blood and causes mental retardation and other abnormalities. Retardation can be prevented if phenylketonuria is diagnosed in the first three weeks of infancy and dietary treatment started straightaway. There is a universal screening test in the UK (the Guthrie test). Heel-prick blood samples are taken from all babies between 6-14 days old and analysed at a regional screening centre. For infants, a phenylalanine-free formula is needed, either as a supplement before breast feeds or following a formula feed. The diet must continue during weaning and childhood, with a low protein diet. Foods such as meat, fish, eggs, milk, cheese, nuts and pulses are excluded as they contain high levels of phenylalanine. Vegetables and fruit are allowed in measured amounts only! Special low protein bread, pasta, biscuits and flour are used to supplement the diet and ensure adequate calorie intake. Whether the diet can be stopped at the end of adolescence is debatable. If stopped, it should be re-started at conception and maintained during pregnancy, as high levels of phenylalanine in the mother can affect the fetus. PMID:9814366

  1. PKU-3: An HCl-Inclusive Aluminoborate for Strecker Reaction Solved by Combining RED and PXRD.

    PubMed

    Chen, Hong; Ju, Jing; Meng, Qingpeng; Su, Jie; Lin, Cong; Zhou, Zhengyang; Li, Guobao; Wang, Weilu; Gao, Wenliang; Zeng, Chunmei; Tang, Chiu; Lin, Jianhua; Yang, Tao; Sun, Junliang

    2015-06-10

    A novel microporous aluminoborate, denoted as PKU-3, was prepared by the boric acid flux method. The structure of PKU-3 was determined by combining the rotation electron diffraction and synchrotron powder X-ray diffraction data with well resolved ordered Cl(-) ions in the channel. Composition and crystal structure analysis showed that there are both proton and chlorine ions in the channels. Part of these protons and chlorine ions can be washed away by basic solutions to activate the open pores. The washed PKU-3 can be used as an efficient catalyst in the Strecker reaction with yields higher than 90%. PMID:26001409

  2. PKU-RBRC Workshop on Transverse Spin

    SciTech Connect

    Avakian,H.; Bunce, G.; Yuan, F.

    2008-06-30

    Understanding the structure of the nucleon is a fundamental question in subatomic physics, and it has been under intensive investigation for the last several years. Modern research focuses in particular on the spin structure of the nucleon. Experimental and theoretical investigations worldwide over the last few decades have established that, contrary to nave quark model expectations, quarks carry only about 30% of the totd spin of the proton. The origin of the remaining spin is the key question in current hadronic physics and also the major driving forces for the current and future experiments, such as RHIC and CEBAF in US, JPARC in Japan, COMPASS at CERN in Europe, FAIR at GSI in Germany. Among these studies, the transverse-spin physics develops actively and rapidly in the last few years. Recent studies reveal that transverse-spin physics is closely related to many fundamental properties of the QCD dynamics such as the factorization, the non-trivial universality of the parton distribution and fragmentation functions. It was very timely to bring together the theorists and experimentalists in this field at this workshop to review and discuss the latest developments and future perspective in hadronic spin physics. This workshop was very success iu many aspects. First of all, it attracted almost every expert working in this field. We had more than eighty participants in total, among them 27 came from the US institutes, 13 from Europe, 3 from Korea, and 2 from Japan. The rest participants came from local institutes in China. Second, we arranged plenty physics presentations, and the program covers all recent progresses made in the last few years. In total, we had 47 physics presentations, and two round table discussions. The discussion sessions were especially very useful and very much appreciated by all participants. In addition, we also scheduled plenty time for discussion in each presentation, and the living discussions impressed and benefited all participants.

  3. Psychological adjustment of children with congenital hypothyroidism and phenylketonuria as related to parental psychological adjustment.

    PubMed

    Jusiene, Roma; Kucinskas, Vaidutis

    2004-01-01

    Phenylketonuria and congenital hypothyroidism are the inherited metabolic diseases that can be diagnosed and successfully treated early from birth. Nevertheless, children with phenylketonuria and congenital hypothyroidism are found to be in the risk for psychological maladjustment. Parental adjustment - as significant condition for child's psychological adjustment--and related factors are explored in this study. Parents of 63 children with congenital hypothyroidism and phenylketonuria (age 2 to 14 years) answered the Child Behavior Checklist, Coping Strategies Questionnaire and the questionnaire on reactions to child's disease, relations with a sick child, with the spouse and other people. Severity of the disease and child's age are considered as well. Results of the study show that parental emotional (maladaptive) coping and indulgence of a sick child account for the higher rates of internalizing problems of children with phenylketonuria and congenital hypothyroidism. In addition, the higher rates of children's psychological problems are related to parental feelings of guilt as a reaction to child's disease. PMID:15252232

  4. Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H- sources

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Zhang, T.; Ren, H. T.; Zhang, A. L.; Xu, Y.; Zhang, J. F.; Guo, Z. Y.; Chen, J. E.

    2016-02-01

    Microwave driven cesium-free volume H- sources, that have the ability to deliver tens of mA H- at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3-8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms, 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H- sources can deliver tens of mA H- at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H- current increases with RF power linearly. Details will be presented in the paper.

  5. Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H⁻ sources.

    PubMed

    Peng, S X; Zhang, T; Ren, H T; Zhang, A L; Xu, Y; Zhang, J F; Guo, Z Y; Chen, J E

    2016-02-01

    Microwave driven cesium-free volume H(-) sources, that have the ability to deliver tens of mA H(-) at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3-8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms, 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H(-) sources can deliver tens of mA H(-) at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H(-) current increases with RF power linearly. Details will be presented in the paper. PMID:26932007

  6. The enigma of the old poet: did the child Wienke in Theodor Storm's novella "Der Schimmelreiter" (1888) have phenylketonuria?

    PubMed

    Urban, M; Nieschlag, A

    2001-11-22

    We report a probable case of phenylketonuria in a figure from "Der Schimmelreiter", a novella by German author Theodor Storm (1817-1888), published in 1888. The child Wienke, daughter of the story's protagonist, Hauke Haien, displays symptoms of phenylketonuria. Storm's description of this child, its physiognomy, and increasing mental retardation, lead us to believe that Storm in fact described a case of phenylketonuria, a condition not reported until Følling's description in 1934. PMID:11746051

  7. Use of an Amino Acid Mixture in Treatment of Phenylketonuria

    PubMed Central

    Bentovim, A.; Clayton, Barbara E.; Francis, Dorothy E. M.; Shepherd, Jean; Wolff, O. H.

    1970-01-01

    Twelve children with phenylketonuria diagnosed and treated from the first few weeks of life were grouped into pairs. Before the trial all of them were receiving a commercial preparation containing a protein hydrolysate low in phenylalanine (Cymogran, Allen and Hanburys Ltd.) as a substitute for natural protein. One of each pair was given an amino acid mixture instead of Cymogran for about 6 months. Use of the mixture involved considerable modification of the diet, and in particular the inclusion of greater amounts of phenylalanine-free foods. All six accepted the new mixture without difficulty, food problems were greatly reduced, parents welcomed the new preparation, and the quality of family life improved. Normal growth was maintained and with a mixture of l amino acids the plasma and urinary amino acid levels were normal. Further studies are needed before the mixture can be recommended for children under 20 months of age. PMID:5477678

  8. Methods of dietary inception in infants with PKU.

    PubMed

    Acosta, P B; Wenz, E; Williamson, M

    1978-02-01

    Information on methods of initiating the phenylalanine-restricted diet was obtained from the medical personnel of sixteen clinics in the Collaborative Study of Children Treated for Phenylketonuria. The four dietary methods used initially to lower serum phenylalanine were: Normal dilution Lofenalac, Lofenalac, with phenylalanine added as milk, Lofenalac with milk added to provide 200 mg. phenylalanine per day, and alternating bottles of normal dilution Lofenalac and cow's milk during the first four days of therapy. During the first week of treatment, eight clinics obtained serum phenylalanine determinations daily or every other day. The nutritionist prescribed the phenylalanine-restricted diet following diagnosis in nine of the clinics. In most clinics, the nutritionist was responsible for obtaining information relating to dietary management and follow-up contacts during the first month of treatment. The initial dietary instruction was accomplished in most clinics by a combination of lecture/discussion/demonstration methods. Both parents attended the initial dietary instruction in thirteen clinics. Neither the professional person(s) nor the method of initial dietary instruction, if detailed and comprehensive, made any difference in control of serum phenylalanine during the first year of life. PMID:624812

  9. Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

    ERIC Educational Resources Information Center

    Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

    1997-01-01

    Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

  10. Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis

    PubMed Central

    de Groot, Martijn J; Sijens, Paul E; Reijngoud, Dirk-Jan; Paans, Anne M; van Spronsen, Francjan J

    2015-01-01

    In phenylketonuria, elevated plasma phenylalanine concentrations may disturb blood-to-brain large neutral amino acid (LNAA) transport and cerebral protein synthesis (CPS). We investigated the associations between these processes, using data obtained by positron emission tomography with l-[1-11C]-tyrosine (11C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for 11C-Tyr transport from arterial plasma to brain tissue (K1), while CPS was modeled by the rate constant for 11C-Tyr incorporation into cerebral protein (k3). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOIs): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k3 and each predictor variable were analyzed by multiple linear regression. The rate constant k3 was inversely associated with brain phenylalanine concentrations in VOIs 2 and 3 (adjusted R2=0.826, F=19.936, P=0.021). Since brain phenylalanine concentrations in these VOIs highly correlated with each other, the specific associations of each predictor with k3 could not be determined. The associations between k3 and plasma phenylalanine concentration, K1, and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k3 and increased brain phenylalanine concentrations. PMID:25352046

  11. An exceptional Albanian family with seven children presenting with dysmorphic features and mental retardation: maternal phenylketonuria

    PubMed Central

    Knerr, Ina; Zschocke, Johannes; Schellmoser, Stefan; Topf, Hans G; Weigel, Corina; Dötsch, Jörg; Rascher, Wolfgang

    2005-01-01

    Background Phenylketonuria is an inborn error of amino acid metabolism which can cause severe damage to the patient or, in the case of maternal phenylketonuria, to the foetus. The maternal phenylketonuria syndrome is caused by high blood phenylalanine concentrations during pregnancy and presents with serious foetal anomalies, especially congenital heart disease, microcephaly and mental retardation. Case presentation We report on an affected Albanian woman and her seven children. The mother is affected by phenylketonuria and is a compound heterozygote for two pathogenetic mutations, L48S and P281L. The diagnosis was only made in the context of her children, all of whom have at least one severe organic malformation. The first child, 17 years old, has a double-chambered right ventricle, vertebral malformations and epilepsy. She is also mentally retarded, microcephalic, exhibits facial dysmorphies and small stature. The second child, a girl 15 years of age, has severe mental retardation with microcephaly, small stature and various dysmorphic features. The next sibling, a boy, died of tetralogy of Fallot at the age of three months. He also had multiple vertebral and rib malformations. The subsequent girl, now eleven years old, has mental retardation, microcephaly and epilepsy along with facial dysmorphy, partial deafness and short stature. The eight-year-old child is slightly mentally retarded and microcephalic. A five-year-old boy was a premature, dystrophic baby and exhibits mental retardation, dysmorphic facial features, brachydactyly and clinodactyly of the fifth finger on both hands. Following a miscarriage, our index case, the youngest child at two years of age, is microcephalic and mentally retarded and shows minor facial anomalies. All children exhibit features of phenylalanine embryopathy caused by maternal phenylketonuria because the mother had not been diagnosed earlier and, therefore, never received any diet. Conclusion This is the largest family suffering

  12. Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation.

    PubMed

    Peng, S X; Zhang, A L; Ren, H T; Zhang, T; Zhang, J F; Xu, Y; Guo, Z Y; Chen, J E

    2016-02-01

    In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observed during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment. PMID:26931924

  13. Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Zhang, A. L.; Ren, H. T.; Zhang, T.; Zhang, J. F.; Xu, Y.; Guo, Z. Y.; Chen, J. E.

    2016-02-01

    In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observed during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment.

  14. Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU Who Were Screened in a National Program

    PubMed Central

    Aghasi, Parisa; Setoodeh, Arya; Sayarifard, Azadeh; Rashidiyan, Maryam; Sayarifard, Fatemeh; Rabbani, Ali; Mahmoudi-Gharaei, Javad

    2015-01-01

    Background: Hyperphenylalaninemia (HPA) and Phenylkeonuria (PKU) are metabolic errors caused by deficiency of phenylalanine hydroxylase enzyme, which results in increased level of phenylalanine. This increase is toxic to the growing brain. Objectives: The purpose of this study was to compare the intellectual and developmental status in HPA and PKU children with normal population in national screening program. Patients and Methods: In a historical cohort study, 41 PKU patients who had the inclusion criteria and 41 healthy children were evaluated. Wechsler preschool and primary scale of intelligence-3rd edition (WPPI-3) was used in order to assess the intellectual status of children 4 years and older and Ages and stages questionnaire (ASQ) was used to assess the developmental status of children 5 years and younger. Results: In intellectual test comparison, the two groups showed significant difference in Wechsler’s performance intelligence score and some performance subscales (P-value < 0.01). In comparison of developmental status, no significant difference was observed between the two groups (P-value > 0.05). Conclusions: Even with early diagnosis and treatment of PKU patients, these children show some deficiencies intellectually compared to normal children. This study emphasizes on necessity for screening intellectual and developmental status of PKU patients so that effective medical or educational measures can taken in case of deficiencies. PMID:26635939

  15. Neuroradiological findings of an adolescent with early treated phenylketonuria: is phenylalanine restriction enough?

    PubMed Central

    Beckhauser, Mayara Thays; Peruchi, Mirella Maccarini; Rozone de Luca, Gizele; Lin, Katia; Esteves, Sofia; Vilarinho, Laura; Lin, Jaime

    2011-01-01

    Phenylketonuria is caused by mutations in the enzyme phenylalanine hydroxylase gene, that can result in abnormal concentrations of phenylalanine on blood, resulting in metabolites that can cause brain damage. The treatment is based on dietary restriction of phenylalanine, and noncompliance with treatment may result in damage of the brain function. Brain abnormalities can be seen on magnetic resonance imaging of these individuals. Studies indicate that the appearance of abnormalities in white matter reflects high levels of phenylalanine on the blood. This case will show the clinical and neuroradiological aspects of a teenager with constant control of phenylalanine levels. Despite the continuous monitoring and early treatment, the magnetic resonance imaging identified impressive abnormalities in the white matter. This leads us to one question: is the restriction of phenylalanine sufficient to prevent changes in the white matter in patients with phenylketonuria? PMID:24765287

  16. Silent mutations in the phenylalanine hydroxylase gene as an aid to the diagnosis of phenylketonuria.

    PubMed Central

    Kalaydjieva, L; Dworniczak, B; Aulehla-Scholz, C; Devoto, M; Romeo, G; Sturhmann, M; Kucinskas, V; Yurgelyavicius, V; Horst, J

    1991-01-01

    Direct sequencing of the phenylalanine hydroxylase (PAH) gene indicated the existence of silent mutations in codons 232, 245, and 385, linked to specific RFLP haplotypes in several Caucasian populations, namely Germans, Bulgarians, Italians, Turks, and Lithuanians. All three mutations create a new restriction site and can be easily detected on PCR amplified DNA. The usefulness of the silent mutations for diagnostic purposes depends on the haplotype distribution in the target population. The combined analysis of these markers and one or two PKU mutations forms a simple panel of diagnostic tests with full informativeness in a large proportion of PKU families, which helps to avoid the problems of genetic heterogeneity and of prenatal genomic Southern blot analysis. Images PMID:1682495

  17. Neonatal Screening Tests.

    ERIC Educational Resources Information Center

    Vigue, Charles L.

    1986-01-01

    Describes several laboratory experiments that are adaptations of clinical tests for certain genetic diseases in babies. Information and procedures are provided for tests for phenylketonuria (PKU), galactosemia, tyrosinemia, cystinuria, and mucopolysaccharidosis. Discusses the effects of each disease on the infants' development. (TW)

  18. Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis.

    PubMed

    Meberg, A; Johansen, K B

    1998-12-01

    In a population-based study including 2463 infants, serum bilirubin measurements were added to the neonatal screening programme for phenylketonuria and congenital hypothyreosis. This screening programme detected 11/17 (65%) of infants with serum bilirubin levels >350 micromol 1(-1), of whom 7 (3 per 1000) were readmitted from home (6 treated with phototherapy). A total of 139 infants (5.6%) received phototherapy. Maternal blood type O occurred significantly more often in term infants treated (30/54; 55.6%) compared with preterm infants treated (32/85; 37.6%) and with blood type O occurrence in the total population of mothers (906/2426; 37.3%) (p < 0.05). The blood type constellations mother O/infant A or B showed a sensitivity of 64%, specificity 65%, positive predictive value 12% and a negative predictive value of 96% for the requirement of phototherapy for the whole material. Exchange transfusion was not required in any of the infants. No infant developed bilirubin encephalopathy (kemicterus). Adding bilirubin to a neonatal screening programme detects some cases with unexpectedly high bilirubin levels in need of intervention. Routine ABO blood typing of pregnant women, ABO cord blood typing and Coombs' test in infants of mothers with blood type O cannot be recommended because of low positive predictive value for the requirement of intervention (phototherapy) by these tests. PMID:9894828

  19. Application of Stacking Technique in ANA: Method and Practice with PKU Seismological Array

    NASA Astrophysics Data System (ADS)

    Liu, J.; Tang, Y.; Ning, J.; Chen, Y. J.

    2010-12-01

    Cross correlation of ambient noise records is now routinely used to get dispersion curve and then do seismic tomography; however little attention has been paid to array techniques. We will present a spacial-stacking method to get high resolution dispersion curves and show practices with the observation data of PKU seismological array. Experiential Green Functions are generally obtained by correlation between two stations, and then the dispersion curves are obtained from the analysis of FTAN. Popular method to get high resolution dispersion curves is using long time records. At the same time, if we want to get effectual signal, the distance between the two stations must be at least 3 times of the longest wavelength. So we need both long time records and appropriate spaced stations. Now we use a new method, special-stacking, which allows shorter observation period and utilizes observations of a group of closely distributed stations to get fine dispersion curves. We correlate observations of every station in the station group with those of a far station, and then stack them together. However we cannot just simply stack them unless the stations in the station group at a circle, of which the center is the far station owing to dispersion characteristics of the Rayleigh waves. Thus we do antidispersion on the observation data of every station in the array, then do stacking. We test the method using the theoretical seismic surface wave records which obtained by qseis06 compiled by Rongjiang Wang both with and without noise. For the cases of three imaginary stations (distance is 1 degree) have the same underground structure and without noise, result is that the center station had the same dispersion with and without spacial-stacking. Then we add noise to the theoretical records. The center station's dispersion curves obtained by our method are much closer to the dispersion curve without noise than contaminated ones. We can see that our method has improved the resolution of

  20. Transcultural pediatrics: compliance and outcome of phenylketonuria patients from families with an immigration background.

    PubMed

    Ipsiroglu, Osman S; Herle, Marion; Spoula, Elisabeth; Möslinger, Dorothea; Wimmer, Banu; Burgard, Peter; Bode, Harald; Stöckler-Ipsiroglu, Sylvia

    2005-08-01

    Living in a foreign country with a different lifestyle and a different orientation is a many-faceted challenge for immigrants. A considerable percentage (30-50%) of patients with metabolic disease come from immigrant families from Turkey and the Middle East. Phenylketonuria is one example of metabolic disease in which severe mental retardation can be entirely prevented by early detection via newborn screening and consistent dietary treatment. We report 7 phenylketonuria patients from 3 Turkish families who had considerable difficulty in coping with the diagnosis and adherence to the diet. Blood phenylalanine levels beyond recommended limits and IQ values below average, clearly demonstrate the risks arising from language as well as psychological and cultural communication barriers, despite standardized follow-up care structures and the observance of continuity by medical caregivers. To propose a basis for systematic improvement in the care of patients from immigrant families we suggest that a) the services of professional interpreters be used in case of language barriers; b) social workers with appropriate sociocultural and language competence should accompany the family in a professional manner; c) it would be meaningful to introduce treatment contracts that clearly establish the limits of the client's rights and duties as well as those of the care-givers. From the viewpoint of legislation, providing medical information is duty of the hospital and the use of translator is mandatory with patients from foreign countries and with foreign languages. PMID:16158204

  1. Converting an injectable protein therapeutic into an oral form: phenylalanine ammonia lyase for phenylketonuria.

    PubMed

    Kang, Tse Siang; Wang, Lin; Sarkissian, Christineh N; Gámez, Alejandra; Scriver, Charles R; Stevens, Raymond C

    2010-01-01

    Phenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; second, we used silica sol-gel material as a matrix to demonstrate that a silica matrix can provide protection to entrapped PAL proteins against intestinal proteases, as well as a low pH of 3.5; finally, we demonstrated that PEGylation of AvPAL surface lysines can reduce the inactivation of the enzyme by trypsin. PMID:19793667

  2. Unusual presentation of two Chinese phenylketonuria sisters who were misdiagnosed for years

    PubMed Central

    Liu, Xiaomei; Guo, Hui; Dahal, Mahesh; Shi, Bingyin

    2013-01-01

    Significant developmental delay was first noticed when both sisters were in their third year of life. However, no biochemical disorders were found through the routine biochemical tests, including liver and kidney function, lipoprotein, urine and blood cell count analysis. Progressively, both sisters exhibited odd behaviour, accompanied by personality changes and altered sleep rhythm and then were diagnosed as attention deficit hyperactivity disorder. In the eighth year, the younger sister began to take risperidone due to a presumed psychiatric disorder. Four months before attending our hospital, both sisters were diagnosed by MRI as having hereditary leukodystrophy. Nerve-nurturing treatment was tried, but without good outcome. They were then referred to our hospital for further consultation. After systematic examinations, it was confirmed that both the sisters were suffering from phenylketonuria. The symptoms were alleviated after dietary restriction of phenylalanine and symptomatic treatment. PMID:24068375

  3. Preparation of a Selective L-Phenylalanine Imprinted Polymer Implicated in Patients with Phenylketonuria

    PubMed Central

    Najafizadeh, Parvaneh; Ebrahimi, Soltan Ahmad; Panjehshahin, Mohammad Reza; Rezayat Sorkhabadi, Seyed Mahdi

    2014-01-01

    Background: Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer (MIP) against l-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid (ESIF). Methods: The MIP for l-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid (MAA), as a functional monomer, and ethylene glycol dimethacrylate (EGDMA), as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran (THF), chloroform, toluene and dimethyl sulfoxide (DMSO). The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM. Results: The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MIP was significantly more than the former binding to NIP in EISF (P≤0.05). Moreover, in comparison with NIP and control group, MIP showed a better selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria. Conclusion: Our findings suggest that the MIP against Phe prepared with acetonitrile, showed a good selectivity and binding, which caused a reduction of blood Phe concentration in enzymatic simulated intestinal fluid and human serum sample of Phenylketonuria. PMID:25429178

  4. Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

    PubMed Central

    Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

    2014-01-01

    Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria. PMID:24464217

  5. White Matter Integrity and Executive Abilities Following Treatment with Tetrahydrobiopterin (BH4) in Individuals with Phenylketonuria

    PubMed Central

    White, Desirée A.; Antenor-Dorsey, Jo Ann V.; Grange, Dorothy K.; Hershey, Tamara; Rutlin, Jerrel; Shimony, Joshua S.; McKinstry, Robert C.; Christ, Shawn E.

    2013-01-01

    Tetrahydrobiopterin (BH4) lowers blood phenylalanine (Phe) in individuals with PKU who are responders, but its effects on the brain and cognition have not been explored thoroughly. We examined blood Phe, microstructural white matter integrity, and executive abilities in 12 BH4 responders before (i.e., baseline) and after (i.e., follow-up) six months of treatment with BH4. Compared with baseline, Phe in these responders decreased by 51% during a 4 week screening period after initiation of treatment and remained lowered by 37% over the 6 month follow-up period. Significant improvements in white matter integrity, evaluated by mean diffusivity from diffusion tensor imaging, were also found following six months of treatment. Improvements in executive abilities were not identified, although six months may have been a period too brief for changes in cognition to follow changes in brain. To our knowledge, our study is the first to explore relationships among Phe, white matter integrity, executive abilities, and BH4 treatment within a single study. PMID:23928118

  6. White matter integrity and executive abilities following treatment with tetrahydrobiopterin (BH4) in individuals with phenylketonuria.

    PubMed

    White, Desirée A; Antenor-Dorsey, Jo Ann V; Grange, Dorothy K; Hershey, Tamara; Rutlin, Jerrel; Shimony, Joshua S; McKinstry, Robert C; Christ, Shawn E

    2013-11-01

    Tetrahydrobiopterin (BH(4)) lowers blood phenylalanine (Phe) in individuals with PKU who are responders, but its effects on the brain and cognition have not been explored thoroughly. We examined blood Phe, microstructural white matter integrity, and executive abilities in 12 BH(4) responders before (i.e., baseline) and after (i.e., follow-up) six months of treatment with BH(4). Compared with baseline, Phe in these responders decreased by 51% during a 4 week screening period after initiation of treatment and remained lowered by 37% over the 6 month follow-up period. Significant improvements in white matter integrity, evaluated by mean diffusivity from diffusion tensor imaging, were also found following six months of treatment. Improvements in executive abilities were not identified, although six months may have been a period too brief for changes in cognition to follow changes in the brain. To our knowledge, our study is the first to explore relationships among Phe, white matter integrity, executive abilities, and BH(4) treatment within a single study. PMID:23928118

  7. Genetic diversity within the R408W phenylketonuria mutation lineages in Europe.

    PubMed

    Tighe, Orna; Dunican, Donncha; O'Neill, Charles; Bertorelle, Giorgio; Beattie, Diane; Graham, Colin; Zschocke, Johannes; Cali, Francesco; Romano, Valentino; Hrabincova, Eva; Kozak, Libor; Nechyporenko, Marina; Livshits, Ludmilla; Guldberg, Per; Jurkowska, Monika; Zekanowski, Cezary; Perez, Belen; Desviat, Lourdes Ruiz; Ugarte, Magdalena; Kucinskas, Vaidutis; Knappskog, Per; Treacy, Eileen; Naughten, Eileen; Tyfield, Linda; Byck, Susan; Scriver, Charles R; Mayne, Philip D; Croke, David T

    2003-04-01

    The R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto-Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNTR) nucleotide sequence variation and tetranucleotide short tandem repeat (STR) allelic associations. Wild-type VNTR-8 chromosomes exhibited two major cassette sequence organizations: (a1)5-b3-b2-c1 and (a1)5-b5-b2-c1. R408W-1.8 was predominantly associated with (a1)5-B5-B2-C1. Both wild-type vntr-3 and r408w-2.3 chromosomes exhibited a single invariant cassette sequence organization, a2-b2-c1. STR allele distributions associated with the cassette variants were consistent with greater diversity in the wild-type VNTR-8 lineage and were suggestive of different levels of diversity between R408W-1.8 and R408W-2.3. The finding of greater genetic diversity within the wild-type VNTR-8 lineage compared to VNTR-3 suggests that VNTR-8 may be older within the European population. However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages. PMID:12655548

  8. Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria.

    PubMed

    Hood, Anna; Antenor-Dorsey, Jo Ann V; Rutlin, Jerrel; Hershey, Tamara; Shimony, Joshua S; McKinstry, Robert C; Grange, Dorothy K; Christ, Shawn E; Steiner, Robert; White, Desiree A

    2015-01-01

    In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (N=36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age. PMID:25481106

  9. Prolonged Exposure to High and Variable Phenylalanine Levels over the Lifetime Predicts Brain White Matter Integrity in Children with Phenylketonuria

    PubMed Central

    Hood, Anna; Antenor-Dorsey, Jo Ann V.; Rutlin, Jerrel; Hershey, Tamara; Shimony, Joshua S.; McKinstry, Robert C.; Grange, Dorothy K.; Christ, Shawn E.; Steiner, Robert; White, Desiree A.

    2014-01-01

    In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (N = 36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age. PMID:25481106

  10. Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria.

    PubMed

    Preissler, Thales; Bristot, Ivi Juliana; Costa, Bruna May Lopes; Fernandes, Elissa Kerli; Rieger, Elenara; Bortoluzzi, Vanessa Trindade; de Franceschi, Itiane Diehl; Dutra-Filho, Carlos Severo; Moreira, José Claudio Fonseca; Wannmacher, Clovis Milton Duval

    2016-06-01

    The aim of this study was to investigate the effects of phenylalanine on oxidative stress and some metabolic parameters in astrocyte cultures from newborn Wistar rats. Astrocytes were cultured under four conditions: control (0.4 mM phenylalanine concentration in the Dulbecco's Modified Eagle Medium (DMEM) solution), Phe addition to achieve 0.5, 1.0 or 1.5 mM final phenylalanine concentrations. After 72 h the astrocytes were separated for the biochemical measurements. Overall measure of mitochondrial function by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell viability measured by lactate dehydrogenase (LDH) assays indicated that phenylalanine induced cell damage at the three concentrations tested. The alteration on the various parameters of oxidative stress indicated that phenylalanine was able to induce free radicals production. Therefore, our results strongly suggest that Phe at concentrations usually found in PKU induces oxidative stress and consequently cell death in astrocytes cultures. Considering the importance of the astrocytes for brain function, it is possible that these astrocytes alterations may contribute to the brain damage found in PKU patients. PMID:26573865

  11. CW/Pulsed H- ion beam generation with PKU Cs-free 2.45 GHz microwave driven ion source

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Ren, H. T.; Xu, Y.; Zhang, T.; Zhang, A. L.; Zhang, J. F.; Zhao, J.; Guo, Z. Y.; Chen, J. E.

    2015-04-01

    Circular accelerators used for positron emission tomography (PET, i.e. accelerator used for make radio isotopes) need several mA of CW H- ion beam for their routine operation. Other facilities, like Space Radio-Environment Simulate Assembly (SPRESA), require less than 10 mA pulsed mode H- beam. Caesium free negative hydrogen ion source is a good choice for those facilities because of its compact structure, easy operation and low cost. Up to now, there is no H- source able to produce very intense H- beams with important variation of the duty factor[1]. Recently, a new version of 2.45 GHz microwave H- ion source was designed at PKU, based on lessons learnt from the previous one. This non cesiated source is very compact thanks to its permanent magnet configuration. Special attention was paid on the design of the discharge chamber structure, electron dumping and extraction system. Source test to produce H- ion beams in pulsed and CW mode was carried out on PKU ion source test bench. In CW mode, a 10.8 mA/30keV H- beam with rms emittance about 0.16 π.mm.mrad has been obtained with only 500 W rf power. The power efficiency reaches 21 mA/kW. In pulsed mode with duty factor of 10% (100Hz/1ms), this compact source can easily deliver 20 mA H- ion beam at 35 keV with rms emittance about 0.2 π.mm.mrad when RF power is set at 2.2 kW (peak power). Several hour successive running operation in both modes and totaling more than 200 hours proves its high quality. The outside dimension of this new H- source body is ϕ116 mm × 124 mm, and the entire H- source infrastructure, including rf matching section, plasma chamber and extraction system, is ϕ310 × 180 mm. The high voltage region is limited with in a ϕ310 mm × 230 mm diagram. Details are given in this paper.

  12. Amino Acid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  13. Contact with Phenylketonurics and Their Families Beyond Pediatric Age: Conclusion from a Survey and Conference

    ERIC Educational Resources Information Center

    Fisch, Robert O.; And Others

    1977-01-01

    Twenty parents of children 12 years and older with PKU (phenylketonuria, a metabolic disorder which if untreated can result in mental retardation) were surveyed to determine their level of knowledge and their needs. (CL)

  14. Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity

    SciTech Connect

    Desviat, L.R.; Perez, B.; De Lucca, M.

    1995-08-01

    Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. In vitro, the V388M mutant enzyme has similar immunoreactive protein and phenylalanine hydroxylase mRNA and had 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous patients. In Spain it has been detected in 5.7% of the mutant alleles and is always associated with haplotype 1.7. This mutation is also present in high frequency in some Latin American countries (Brazil, 9% Chile, 13%). It is interesting that in Chile most of the alleles bearing this mutation carry haplotype 4.3, although in Brazil it is found only on the background of haplotype 1.7. The origin of V388M in Spain on haplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recurrence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutation from haplotype 1 to 4 is unlikely. 29 refs., 2 figs., 3 tabs.

  15. Phenylalanine-restricted diet should be life long. A case report on long-term follow-up of an adolescent with untreated phenylketonuria.

    PubMed

    Merrick, Joav; Aspler, Shoshana; Schwarz, Gerard

    2003-01-01

    The aim of this brief report is to stimulate a debate and to advocate life-long treatment with phenylalanine restricted diet to persons with phenylketonuria. We present a case of an adolescent male who today is a 65 year old with moderate mental retardation. He was previously observed as having severe challenging and self-injurious behaviour, sleeping disorder, hyperactivity, and masturbation. In the last year before reassessment he displayed loss of weight, muscle weakness resulting in wheelchair placement, upper respiratory infections, and fungal skin infections. After reassessment in 1998 the patient was started on treatment with a phenylalanine-restricted diet supplemented with vitamin B12, iron, and folic acid. At follow-up one year later the patient had regained his weight and was walking around freely. The challenging and self-injurious behaviour, and the masturbation, had ceased, and he was participating in social activities which he had previously not been able to participate in. At follow-up four years later he was still at this level of accomplishment. In general, this patient's quality of life had increased. We therefore recommend life-long treatment with phenylalanine restricted diet for persons with previously treated, and also for those with untreated, phenylketonuria. PMID:12955819

  16. Diseases of Phenylalanine Metabolism

    PubMed Central

    Parker, Charles E.

    1979-01-01

    Continuing investigation of the system that hydroxylates phenylalanine to tyrosine has led to new insights into diseases associated with the malfunction of this system. Good evidence has confirmed that phenylketonuria (PKU) is not caused by a simple lack of phenylalanine hydroxylase. Dihydropteridine reductase deficiency as well as defects in biopterin metabolism may also cause the clinical features of phenylketonuria. Furthermore, these diseases do not respond to the standard treatment for phenylketonuria. PMID:388868

  17. Dictyostelium discoideum Ax2 as an Assay System for Screening of Pharmacological Chaperones for Phenylketonuria Mutations.

    PubMed

    Kim, Yu-Min; Yang, Yun Gyeong; Kim, Hye-Lim; Park, Young Shik

    2015-06-01

    In this study, we developed an assay system for missense mutations in human phenylalanine hydroxylases (hPAHs). To demonstrate the reliability of the system, eight mutant proteins (F39L, K42I, L48S, I65T, R252Q, L255V, S349L, and R408W) were expressed in a mutant strain (pah(-)) of Dictyostelium discoideum Ax2 disrupted in the indigenous gene encoding PAH. The transformed pah- cells grown in FM minimal medium were measured for growth rate and PAH activity to reveal a positive correlation between them. The protein level of hPAH was also determined by western blotting to show the impact of each mutation on protein stability and catalytic activity. The result was highly compatible with the previous ones obtained from other expression systems, suggesting that Dictyostelium is a dependable alternative to other expression systems. Furthermore, we found that both the protein level and activity of S349L and R408W, which were impaired severely in protein stability, were rescued in HL5 nutrient medium. Although the responsible component(s) remains unidentified, this unexpected finding showed an important advantage of our expression system for studying unstable proteins. As an economic and stable cell-based expression system, our development will contribute to mass-screening of pharmacological chaperones for missense PAH mutations as well as to the in-depth characterization of individual mutations. PMID:25563416

  18. [Psychomotor retardation and intermitent convulsions for 8 months in an infant].

    PubMed

    Ding, Yuan; Li, Xi-Yuan; Liu, Yu-Peng; Li, Dong-Xiao; Song, Jin-Qing; Li, Meng-Qiu; Qin, Ya-Ping; Wu, Tong-Fei; Yang, Yan-Ling

    2016-01-01

    This study reports a boy with psychomotor retardation and epilepsy due to maternal phenylketonuria (PKU). The boy was admitted at the age of 20 months because of psychomotor retardation and epilepsy. He had seizures from the age of 1 year. His development quotient was 43. He presented with microcephaly, normal skin and hair color. Brain MRI scan showed mild cerebral white matter demyelination, broadening bilateral lateral ventricle and foramen magnum stricture. Chromosome karyotype, urine organic acids, blood amino acids and acylcarnitines were normal. His mother had mental retardation from her childhood. She presented with learning difficulties and yellow hair. Her premarriage health examinations were normal. She married a healthy man at age of 26 years. When she visited us at 28 years old, PKU was found by markedly elevated blood phenylalanine (916.54 μmol/L vs normal range 20-120 μmol/L). On her phenylalanine hydroxylase (PAH) gene, a homozygous mutations c.611A>G (p.Y204C) was identified, which confirmed the diagnosis of PAH-deficient PKU. Her child carries a heterozygous mutation c.611A>G with normal blood phenylalanine. Her husband had no any mutation on PAH. It is concluded that family investigation is very important for the etiological diagnosis of the children with mental retardation and epilepsy. Carefully clinical and metabolic survey should be performed for the parents with mental problems to identify parental diseases-associated child brain damage, such as maternal PKU. PMID:26781416

  19. Phenylketonuria—Experience at One Center in the First Year of Screening in California

    PubMed Central

    Peterson, Raymond M.; Koch, Richard; Schaeffler, Graciela E.; Wohlers, Audrey; Acosta, Phyllis B.; Boyle, David

    1968-01-01

    One year's experience with phenylketonuria during the calendar year 1966, the first year for compulsory newborn screening in California, was reviewed. The over-all prevalence rate from reported cases in California during this period was one case per 19,500 persons tested. Fifty-seven persons suspected of having pku were evaluated, and 25 of them were determined to be phenylketonuric. Eleven of the 25 were infants in whom the abnormality was detected through the newborn screening program or because it was detected in a sibling through a screening program. All the newborn phenylketonuric patients were developing normally at the time of last report (although the follow-up periods were short). In nine of the other children, pku was detected because they were retarded. Five retarded children who were diagnosed as phenylketonuric at another clinic were given dietary assistance. Five additional infants had elevated serum phenylalanines but did not have the classic biochemical findings of pku and are being evaluated further. Nine infants with positive screening tests exhibited biochemical and clinical findings consistent with transient tyrosinemia. Eighteen other children were evaluated and found to have no metabolic abnormality. The newborn screening program for pku is of decided benefit in early identification of a group of infants who have a high rate of potentially serious metabolic disease. Early identification permits treatment soon enough to prevent mental retardation. Newly identified patients should be evaluated in a medical setting capable of careful pediatric, biochemical and nutritional surveillance. PMID:5652755

  20. CW/Pulsed H{sup −} ion beam generation with PKU Cs-free 2.45 GHz microwave driven ion source

    SciTech Connect

    Peng, S. X. Ren, H. T.; Xu, Y.; Zhang, T.; Zhang, J. F.; Zhao, J.; Guo, Z. Y.; Zhang, A. L.; Chen, J. E.

    2015-04-08

    Circular accelerators used for positron emission tomography (PET, i.e. accelerator used for make radio isotopes) need several mA of CW H- ion beam for their routine operation. Other facilities, like Space Radio-Environment Simulate Assembly (SPRESA), require less than 10 mA pulsed mode H{sup −} beam. Caesium free negative hydrogen ion source is a good choice for those facilities because of its compact structure, easy operation and low cost. Up to now, there is no H{sup −} source able to produce very intense H{sup −} beams with important variation of the duty factor{sup [1]}. Recently, a new version of 2.45 GHz microwave H{sup −} ion source was designed at PKU, based on lessons learnt from the previous one. This non cesiated source is very compact thanks to its permanent magnet configuration. Special attention was paid on the design of the discharge chamber structure, electron dumping and extraction system. Source test to produce H{sup −} ion beams in pulsed and CW mode was carried out on PKU ion source test bench. In CW mode, a 10.8 mA/30keV H{sup −} beam with rms emittance about 0.16 π·mm·mrad has been obtained with only 500 W rf power. The power efficiency reaches 21 mA/kW. In pulsed mode with duty factor of 10% (100Hz/1ms), this compact source can easily deliver 20 mA H{sup −} ion beam at 35 keV with rms emittance about 0.2 π·mm·mrad when RF power is set at 2.2 kW (peak power). Several hour successive running operation in both modes and totaling more than 200 hours proves its high quality. The outside dimension of this new H{sup −} source body is ϕ116 mm × 124 mm, and the entire H{sup −} source infrastructure, including rf matching section, plasma chamber and extraction system, is ϕ310 × 180 mm. The high voltage region is limited with in a ϕ310 mm × 230 mm diagram. Details are given in this paper.

  1. Phenylketonuria Genetic Screening Simulation

    ERIC Educational Resources Information Center

    Erickson, Patti

    2012-01-01

    After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

  2. Genetics Home Reference: phenylketonuria

    MedlinePlus

    ... Phenylalanine is a building block of proteins ( an amino acid ) that is obtained through the diet. It is ... enzyme called phenylalanine hydroxylase . This enzyme converts the amino acid phenylalanine to other important compounds in the body. ...

  3. Showing Value in Newborn Screening: Challenges in Quantifying the Effectiveness and Cost-Effectiveness of Early Detection of Phenylketonuria and Cystic Fibrosis

    PubMed Central

    Grosse, Scott D.

    2015-01-01

    Decision makers sometimes request information on the cost savings, cost-effectiveness, or cost-benefit of public health programs. In practice, quantifying the health and economic benefits of population-level screening programs such as newborn screening (NBS) is challenging. It requires that one specify the frequencies of health outcomes and events, such as hospitalizations, for a cohort of children with a given condition under two different scenarios—with or without NBS. Such analyses also assume that everything else, including treatments, is the same between groups. Lack of comparable data for representative screened and unscreened cohorts that are exposed to the same treatments following diagnosis can result in either under- or over-statement of differences. Accordingly, the benefits of early detection may be understated or overstated. This paper illustrates these common problems through a review of past economic evaluations of screening for two historically significant conditions, phenylketonuria and cystic fibrosis. In both examples qualitative judgments about the value of prompt identification and early treatment to an affected child were more influential than specific numerical estimates of lives or costs saved. PMID:26702401

  4. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example.

    PubMed

    Camp, Kathryn M; Lloyd-Puryear, Michele A; Huntington, Kathleen L

    2012-09-01

    Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment. PMID:22854513

  5. ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt.

    PubMed

    Saad, Khaled; Elserogy, Yasser; Abdel Rahman, Ahmed A; Al-Atram, Abdulrahman Abdullah; Mohamad, Ismail L; ElMelegy, Tarek T H; Bjørklund, Geir; El-Houfy, Amira A

    2015-12-01

    The aim of this study is to evaluate the neuropsychological status in a cohort of children with early and continuously treated phenylketonuria in Assiut, Upper Egypt. The study was implemented in seventy-eight phenylketonuria (PKU) children. Only 34 patients met the inclusion criteria. Investigated patients were evaluated according to detailed history, neurological examination, Childhood Autism Rating Scale, full scale Intelligence Quotient, attention deficit hyperactivity disorder, electroencephalography and magnetic resonance imaging (MRI). This study concluded that the prognosis for early diagnosed children with PKU treated from the first weeks of life is generally good. However, they are at increased risk for neurological complications and behavioral problems. So, neonatal screening for PKU is highly recommended in Egypt, for early detection and management. In addition, neuropsychological and MRI assessments in PKU children should be done. PMID:25576444

  6. Untreated non-phenylketonuric-hyperphenylalaninaemia: intellectual and neurological outcome.

    PubMed

    Weglage, J; Ullrich, K; Pietsch, M; Fünders, B; Zass, R; Koch, H G

    1996-07-01

    The intellectual, neurological, and neuropsychological outcome of patients with non-phenylketonuric-hyperphenylalaninaemia (PKU-HPA) (serum phenylalanine levels under free diet < 600 mumol/l) has not been systematically studied so far. We therefore tested 28 patients (mean age = 21.8, SD = 4.2 years) for IQ (WAIS-R/WISC-R), school performance, job career, clinical neurological examination, fine motor performance (motor performance task), and selective and sustained attention (stroop task, Dot Pattern Exercise from the Sonneville visual attention task). In addition, cranial MRI (1.5 T unit) was obtained in 10 of these patients. Clinical-neurological examination revealed no significant abnormalities in the non-PKU-HPA patients. They also had a normal IQ (mean = 101.9, SD = 13.6). Compared to their healthy siblings, they attended a normal school and had a normal job career. The motor performance task revealed no deficits in fine motor abilities. The patients performed normally in the stroop task and the dot pattern exercise. Their MRIs were normal. Our results indicate that patients with non-PKU-HPA are not at risk for developing intellectual, neurological, and neuropsychological impairment, as described for patients with treated mild or classical phenylketonuria. From this point of view a dietary treatment is not necessary in patients with hyperphenylalaninaemia. PMID:8828604

  7. Current Status of Newborn Screening: Decision-Making about the Conditions to Include in Screening Programs

    ERIC Educational Resources Information Center

    Watson, Michael S.

    2006-01-01

    Newborn screening is considered a highly successful public health program that has resulted in the reduction of mortality, mental retardation, and other serious disabilities in thousands of children since the introduction of screening for phenylketonuria (PKU) in the 1960s. Programs are based in state public health departments such that each state…

  8. SOME FACTS AND FIGURES ABOUT CHILDREN AND YOUTH.

    ERIC Educational Resources Information Center

    Children's Bureau (DHEW), Washington, DC.

    IN QUESTION AND ANSWER FORM, THE PAMPHLET PRESENTS STATISTICAL DATA ON CHILDREN AND YOUTH PRIMARILY IN THE UNITED STATES. INFORMATION CONCERNS POPULATION, RESIDENCE, MOBILITY, POVERTY, WORKING MOTHERS, MARRIAGES, DIVORCES, BIRTHS, LIFE EXPECTANCY, MORTALITY, ILLNESS, HANDICAPS, HOSPITALIZATION, ADOPTIONS, PHENYLKETONURIA (PKU) LAWS, CHILD ABUSE…

  9. Monkey Retardate Learning Analysis

    ERIC Educational Resources Information Center

    Chamove, A. S.; Molinaro, T. J.

    1978-01-01

    Seven rhesus monkeys reared on diets high in phenylalanine to induce phenylketonuria (PKU--a metabolic disorder associated with mental retardation if untreated) were compared with normal, pair-fed, and younger controls; frontal brain-lesioned monkeys; and those raised on high-tryptophan diets in three object discrimination tasks. (Author)

  10. Genetic background of hyperphenylalaninemia in Nagasaki, Japan.

    PubMed

    Dateki, Sumito; Watanabe, Satoshi; Nakatomi, Akiko; Kinoshita, Eiichi; Matsumoto, Tadashi; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki

    2016-05-01

    Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA. Homozygous or compound heterozygous PAH mutations were identified in all the patients. The spectrum of PAH mutations in the cohort was broad and similar to those in all parts of Japan and East Asian countries. R53H is the most common mutation in patients with mild HPA. The present results provide further support for genotype-phenotype correlations in patients with HPA. The high incidence of PKU in Nagasaki, the westernmost part of Japan, might be due to migration of people with PAH mutations from China and Korea, and geographic factors. PMID:27173423

  11. Molecular newborn screening of four genetic diseases in Guizhou Province of South China.

    PubMed

    Huang, Shengwen; Xu, Yin; Liu, Xingmei; Zhou, Man; Wu, Xian; Jia, Yankai

    2016-10-10

    Genetic disorders have been a major concern for public health in China, especially in the rural regions. However, there is little information available about prevalence of many common single-gene disorders in Guizhou Province in the south western part of China. In the present study, we performed a molecular newborn screening for four genetic disorders, including beta-thalassemia (β-thal), glucose-6-phosphate dehydrogenase (G6PD) deficiency, phenylketonuria (PKU), and non-syndromic hearing loss and deafness (NSHL) in this region. A total of 515 newborns were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) developed for screening the mutations causing these four disorders, and then confirmed by Sanger sequencing. The results showed that 48 out of 515 newborns were carriers of mutations related to these four diseases, with a frequency of 1 in 11 (9.32%). The carrier frequencies for each disease are: β-thal 2.72%; G6PD deficiency 1.94%; PKU 0.78% and NSHL 4.47%. The genotyping results by MALDI-TOF MS were concordant with Sanger sequencing results within 30 randomly selected samples. This is the first study that reveals carrier frequencies of these four diseases in Guizhou Province. These data provide valuable information for the genetic counseling and disease prevention in Guizhou and southwest China. PMID:27395428

  12. [Risk-sharing scheme in Israel--Kuvan as an allegory].

    PubMed

    Abadi-Korek, Ifat; Shemer, Joshua

    2012-06-01

    Healthcare systems worldwide are dealing with the uncertainty characterizing new and expensive health technoLogies, particularly aspects involving drug effectiveness and the extent and doses required for utilization. Reducing this uncertainty can be achieved mainly by using either coverage with evidence development methods or risk-sharing schemes (RSS). In 2011, the first phenylketonuria (PKU) risk-sharing scheme was set up in Israel, through the public funding health services updating process. This was done in order to ensure that people with PKU could access PKU sole treatment--sapropterin dihydrochloride, Kuvan. The apparent effectiveness of the treatment, on one hand, and the uncertainty regarding the number of patients and average treatment dosage, on the other hand, dictated the RRS. This scheme determined a ceiling number of tablets to be funded by the insurer, above this ceiling the manufacturer would finance Kuvan. Furthermore, it was agreed that after 3 years Kuvan would be brought to the public committee for updating reimbursement decisions. It is inevitable that risk sharing and conditional coverage agreements will become a common practice in the reimbursement process in the future. This will allow competent authorities and pharmaceutical companies to build clinical experience and other required data with medicines which might normally not be eLigible for reimbursement. Before it becomes the common practice in Israel, the RSS for Kuvan, process and outcomes, should be monitored and analyzed by the Ministry of Health, to ensure patients access to treatment, the effective collection of the research data and the effective interaction between Israel's four health funds and the manufacturer. PMID:22991868

  13. Differential Effects of Low-Phenylalanine Protein Sources on Brain Neurotransmitters and Behavior in C57Bl/6-Pahenu2 Mice

    PubMed Central

    Sawin, Emily A.; Murali, Sangita G.; Ney, Denise M.

    2014-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase, which metabolizes phenylalanine (phe) to tyrosine. A low-phe diet plus amino acid (AA) formula is necessary to prevent cognitive impairment; glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to the AA formula. Our objective was to assess neurotransmitter concentrations in brain and the behavioral phenotype of PKU mice (Pahenu2 on the C57Bl/6 background) and how this is affected by low-phe protein sources. Wild type (WT) and PKU mice, both male and female, were fed high-phe casein, low-phe AA, or low-phe GMP diets between 3–18 weeks of age. Behavioral phenotype was assessed using the open field and marble burying tests, and brain neurotransmitter concentration measured using HPLC with electrochemical detection system. Data were analyzed by 3-way ANOVA with genotype, sex, and diet as the main treatment effects. Brain mass and the concentrations of catecholamines and serotonin were reduced in PKU mice compared to WT mice; the low-phe AA and GMP diets improved these parameters in PKU mice. Relative brain mass was increased in female PKU mice fed the GMP diet compared to the AA diet. PKU mice exhibited hyperactivity and impaired vertical exploration compared to their WT littermates during the open field test. Regardless of genotype or diet, female mice demonstrated increased vertical activity time and increased total ambulatory and horizontal activity counts compared with male mice. PKU mice fed the high-phe casein diet buried significantly fewer marbles than WT control mice fed casein; this was normalized in PKU mice fed the low-phe AA and GMP diets. In summary, C57Bl/6-Pahenu2 mice showed an impaired behavioral phenotype and reduced brain neurotransmitter concentrations that were improved by the low-phe AA or GMP diets. These data support lifelong adherence to a low-phe diet for PKU. PMID:24560888

  14. Using simple molecular orbital calculations to predict disease: fast DFT methods applied to enzymes implicated in PKU, Parkinson's disease and Obsessive Compulsive Disorder

    NASA Astrophysics Data System (ADS)

    Hofto, Laura; Hofto, Meghan; Cross, Jessica; Cafiero, Mauricio

    2007-09-01

    Many diseases can be traced to point mutations in the DNA coding for specific enzymes. These point mutations result in the change of one amino acid residue in the enzyme. We have developed a model using simple molecular orbital calculations which can be used to quantitatively determine the change in interaction between the enzyme's active site and necessary ligands upon mutation. We have applied this model to three hydroxylase proteins: phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase, and we have obtained excellent correlation between our results and observed disease symptoms. Furthermore, we are able to use this agreement as a baseline to screen other mutations which may also cause onset of disease symptoms. Our focus is on systems where the binding is due largely to dispersion, which is much more difficult to model inexpensively than pure electrostatic interactions. Our calculations are run in parallel on a sixteen processor cluster of 64-bit Athlon processors.

  15. Genetic heterogeneity in five Italian regions: analysis of PAH mutations and minihaplotypes.

    PubMed

    Giannattasio, S; Dianzani, I; Lattanzio, P; Spada, M; Romano, V; Calì, F; Andria, G; Ponzone, A; Marra, E; Piazza, A

    2001-01-01

    Molecular analysis of 289 chromosomes has been performed in a cohort of phenylketonuria (PKU) patients whose ancestors lived in five Italian regions, Calabria, Campania, Piemonte, Puglia/Basilicata and Sicilia. Phenylalaninehydroxylase (PAH) gene mutations and minihaplotypes (combinations of PAH gene STR and VNTR systems) have been determined for 78.5 and 64%, respectively, of the chromosomes studied. 21 different minihaplotypes and 24 PKU mutations were found. Heterogeneity tests carried out for the frequencies of mutations and minihaplotypes show that the distribution of eight mutations and four minihaplotypes is statistically heterogeneous in the five Italian regions. Although the evolutionary rate of microsatellites or the age of these mutations is difficult to estimate with accuracy, our findings taken together show a genetic stratification of the Italian population. These results rule out allelic homogeneity of PKU at the molecular level between regions of Italy, yet minihaplotype data may be of practical use for a multistep approach to PAH gene genotyping. PMID:11588399

  16. Essentials of PKU for Young Adults with PKU and Their Significant Others

    MedlinePlus

    ... low-phenylalanine food pattern. Food records Often the nutritionist will request a diet record. A diet record ... for each individual's taste, body size, nutritional needs, personal preferences and cooking skills. Just as a person ...

  17. Vitamin and mineral status in patients with hyperphenylalaninemia.

    PubMed

    Crujeiras, Vanesa; Aldámiz-Echevarría, Luis; Dalmau, Jaime; Vitoria, Isidro; Andrade, Fernando; Roca, Iria; Leis, Rosaura; Fernandez-Marmiesse, Ana; Couce, María L

    2015-08-01

    Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) treated patients, who should receive optimal supplementation although this is not yet fully established. We conducted a cross-sectional observational multicenter study including 156 patients with hyperphenylalaninemia. Patients were stratified by age, phenotype, disease detection and type of treatment. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, and biochemical parameters (total protein, prealbumin, electrolytes, selenium, zinc, B12, folic acid, ferritin, 25-OH vitamin D) were collected in all patients. 81.4% of patients had biochemical markers out of recommended range but no clinical symptoms. Total protein, calcium, phosphorus, B12, ferritin, and zinc levels were normal in most patients. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18 years old), showing almost all (96.3%) an adequate adherence to diet. Selenium was diminished in 25% of patients (95% with PKU phenotype) and also 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B12 levels were found diminished in patients with low adherence to diet. Patients under BH4 therapy only showed significant lower levels of B12. This study shows a high percentage of prealbumin and selenium deficiencies as well as an increased level of folic acid in PKU treated patients, which should lead us to assess an adjustment for standards supplements formulated milks. PMID:26123187

  18. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

    PubMed

    Wolf-Novak, L C; Stegink, L D; Brummel, M C; Persoon, T J; Filer, L J; Bell, E F; Ziegler, E E; Krause, W L

    1990-04-01

    Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals. PMID:2182973

  19. Development

    ERIC Educational Resources Information Center

    Childress, Dana C.; Raver, Sharon A.; Michalek, Anne M. P.; Wilson, Corinne L.

    2013-01-01

    All eligible infants and toddlers who receive early intervention services under Part C of Individuals with Disabilities Education Act are entitled to service coordination. To examine the effectiveness of one state's service coordination training and its impact on knowledge and skill development, a pretest--posttest design with follow-up…

  20. Differential effects of low-phenylalanine protein sources on brain neurotransmitters and behavior in C57Bl/6-Pah(enu2) mice.

    PubMed

    Sawin, Emily A; Murali, Sangita G; Ney, Denise M

    2014-04-01

    Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase, which metabolizes phenylalanine (phe) to tyrosine. A low-phe diet plus amino acid (AA) formula is necessary to prevent cognitive impairment; glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to the AA formula. Our objective was to assess neurotransmitter concentrations in the brain and the behavioral phenotype of PKU mice (Pah(enu2) on the C57Bl/6 background) and how this is affected by low-phe protein sources. Wild type (WT) and PKU mice, both male and female, were fed high-phe casein, low-phe AA, or low-phe GMP diets between 3 and 18 weeks of age. Behavioral phenotype was assessed using the open field and marble burying tests, and brain neurotransmitter concentrations were measured using HPLC with electrochemical detection system. Data were analyzed by 3-way ANOVA with genotype, sex, and diet as the main treatment effects. Brain mass and the concentrations of catecholamines and serotonin were reduced in PKU mice compared to WT mice; the low-phe AA and GMP diets improved these parameters in PKU mice. Relative brain mass was increased in female PKU mice fed the GMP diet compared to the AA diet. PKU mice exhibited hyperactivity and impaired vertical exploration compared to their WT littermates during the open field test. Regardless of genotype or diet, female mice demonstrated increased vertical activity time and increased total ambulatory and horizontal activity counts compared with male mice. PKU mice fed the high-phe casein diet buried significantly fewer marbles than WT control mice fed casein; this was normalized in PKU mice fed the low-phe AA and GMP diets. In summary, C57Bl/6-Pah(enu2) mice showed an impaired behavioral phenotype and reduced brain neurotransmitter concentrations that were improved by the low-phe AA or GMP diets. These data support lifelong adherence to a low-phe diet for PKU. PMID:24560888

  1. Options in Education, Transcript for April 12, 1976: Review of "Simple Justice," Writing Seminars for Judges and Lawyers, The Teaching of Writing, Visual Literacy, Teacher Internships, System of Interactive Guidance, Changing Jobs, and PKU Children.

    ERIC Educational Resources Information Center

    George Washington Univ., Washington, DC. Inst. for Educational Leadership.

    "Options in Education" is a radio news program which focuses on issues and developments in education. This transcript contains discussions of the book "Simple Justice" by Richard Kluger; writing seminars for judges and lawyers, held by the American Academy of Judicial Education; the teaching of writing; visual literacy--picture words; teacher…

  2. Intellectual performance of children with maple syrup urine disease.

    PubMed

    Hilliges, C; Awiszus, D; Wendel, U

    1993-02-01

    The intellectual performance of 22 children aged 3-16 years with maple syrup urine disease (MSUD) was assessed and compared to a group of early treated phenylketonuria (PKU) children and normal subjects matched by age, sex, nationality, and socio-economic status. All subjects were tested by one examiner only using the age related versions of the non-verbal Snijders-Oomen intelligence test. The mean IQ (+/- SD) score was 74 +/- 14 (range 50-103) in patients with MSUD, 101 +/- 12 (range 87-125) in early treated PKU patients, and 107 +/- 9 (range 90-122) in normal subjects. Intercorrelations indicated that length of time after birth that plasma leucine concentration remained > 1 mmol/l and quality of long-term metabolic control have important influences on IQ. PMID:8444223

  3. [Neurological, neuropsychological, and ophthalmological evolution after one year of docosahexaenoic acid supplementation in phenylketonuric patients].

    PubMed

    Gutiérrez-Mata, Alfonso P; Vilaseca, M Antonia; Capdevila-Cirera, Antoni; Vidal-Oller, Mariona; Alonso-Colmenero, Itziar; Colomé, Roser; López-Sala, Anna; Lambruschini-Ferri, Nilo; Gutiérrez, Alejandra; Gassió, Rosa; Artuch, Rafael; Campistol, Jaume

    2012-08-16

    INTRODUCTION. Phenylketonuria (PKU) is an autosomal recessive metabolic disease caused by a deficiency of phenylalanine hydroxylase. The dietary therapy for the effective management of PKU, in particular the restriction of high-protein foods of animal-origin, compromises patients' intake of fat and distorts the n-3:n-6 ratio of essential fatty acids in the diet. This deficiency can contribute to neurological and visual impairment. AIM. To evaluate changes in white matter alterations, visual evoked potential (VEP) latencies and performance in executive and motor functions in a group of early and continuously treated PKU patients after supplementation with docosahexaneoic acid (DHA). PATIENTS AND METHODS. We selected 21 PKU patients with early diagnosis (age range: 9-25 years), on a Phe-restricted diet and supplemented with PKU formula. Inclusion criteria were: low erythrocyte DHA values, prolonged P100 wave latencies in VEP and/or presence of white matter hyperintensities on brain magnetic resonance imaging (MRI), and intellectual quotient > 80. All patients were treated with DHA (10 mg/kg/day) for 12 months. Assessment was conducted at baseline and after 12 months of treatment, and included biochemical parameters, brain MRI, VEP, ophthalmologic evaluation and neuropsychological tests. RESULTS AND CONCLUSION. All the patients normalized the DHA levels after supplementation. Improvement in the P100 wave latencies, and fine motor skills was significant. No significant improvement in the other explorations was evident after supplementation. Further investigations seem advisable to establish a cause-effect relationship between DHA treatment and the slight improvement observed in some neurological functions. PMID:22829083

  4. Normal vitamin D levels and bone mineral density among children with inborn errors of metabolism consuming medical food-based diets.

    PubMed

    Geiger, Katie E; Koeller, David M; Harding, Cary O; Huntington, Kathleen L; Gillingham, Melanie B

    2016-01-01

    A higher incidence of osteopenia is observed among children with inherited metabolic disorders (inborn errors of metabolism, or IEMs) who consume medical food-based diets that restrict natural vitamin D-containing food sources. We evaluated the vitamin D status of children with IEMs who live in the Pacific Northwest with limited sun exposure and determined whether bone mineral density (BMD) in children with phenylketonuria (PKU), the most common IEM, correlated with diet or biochemical markers of bone metabolism. We hypothesized that children with IEMs would have lower serum vitamin D concentrations than controls and that some children with PKU would have reduced bone mineralization. A retrospective record review of 88 patients with IEMs, and 445 children on unrestricted diets (controls) found the 25-hydroxyvitamin D concentrations were normal and not significantly different between groups (IEM patients, 27.1 ± 10.9; controls, 27.6 ± 11.2). Normal BMD at the hip or spine (-2 PKU. There was a correlation between lumbar spine BMD and dietary calcium intake. We saw no evidence of low serum vitamin D in our population of children with IEMs compared with control children. We also found no evidence for reduced BMD in children with PKU on specialized diets, but BMD was associated with calcium intake. Dietary intake of essential nutrients in medical food-based diets supports normal 25-hydroxyvitamin D levels and BMD in children with IEMs, including PKU. The risk of vitamin D deficiency among patients consuming a medical food-based diet is similar to the general population. PMID:26773786

  5. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  6. Neonatal screening in Italy for congenital hypothyroidism and metabolic disorders: hyperphenylalaninemia, maple syrup urine disease and homocystinuria.

    PubMed

    Antonozzi, I; Dominici, R; Andreoli, M; Monaco, F

    1980-01-01

    A multiple screening program to establish the frequency of congenital hypothyroidism (CH), phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria and hypertyrosinemia in endemic and sporadic goitrous regions of Italy is being carried out. Valine, methionine, leucine, isoleucine, tyrosine and phenylalanine, eluted from a single spot and separated by column chromatography, are measured, using whole blood adsorbed on filter paper. CH is detected by RIA assay of TSH eluted from dried blood spot. A cut-off of 100 microU/ml for TSH is used providing a recall rate of 0.38%. Out of 116,000 newborn infants screened for aminoacidopathies (since 1974), 16 PKU patients, 3 affected by MSUD, 2 homocystinuric babies have been detected. Out of 25,400 newborn infants screened for CH, 5 patients were affected by permanent CH and 29 by transient hyperthyrotropinemia. Thus PKU shows a frequency of 1:7,200 newborn infants, and permanent congenital hypothyroidism 1:5,080. The coordination of screening programs for congenital metabolic diseases in a single central unit allows:--the unification of the input of samples and output of data in a single data bank;--a minimization of the physical and psychological stress to the patients and their families;--and a more satisfactory cost/benefit ratio. PMID:7204885

  7. Complete spectrum of PAH mutations in Tataria: presence of Slavic, Turkic and Scandinavian mutations.

    PubMed

    Kuzmin, A I; Eisensmith, R C; Goltsov, A A; Sergeeva, N A; Schwartz, E I; Woo, S L

    1995-01-01

    Phenylketonuria (PKU) is an autosomal recessive disorder associated with a deficiency of hepatic phenylalanine hydroxylase (PAH). Although the molecular lesions present in the PAH genes of PKU patients have previously been determined in several Slavic populations, little is known regarding the molecular basis of PKU in the non-Slavic populations of the former Soviet Union. Guthrie card samples from twenty-one classical PKU patients residing in the Tatarian Republic were examined by a combination of denaturing gradient gel electrophoresis and direct sequence analysis. Twelve patients were of Tatarian ancestry, five were of Russian ancestry, and four were of mixed Tatarian and Russian ancestry. Two of the Tatarian patients were related, sharing one mutant allele. The single major allele identified in this study was R408W/RFLP haplotype 2/VNTR 3, which was present on 11/14 or 78.6% of all mutant chromosomes of Slavic origin, but on only 10/27 or 37.0% of mutant chromosomes of Tatarian origin. This result suggests that this allele was introduced into central Asian populations during the eastward expansion of Slavs across the Eurasian landmass. A significant influence of Turkic peoples on Tatars can be inferred from the presence of R261Q. IVS10nt546g --> a, L48S, IVS2nt5g --> c and P281L, all of which are relatively common among Turks or have been observed in Mediterranean populations. Together, these alleles are present on 11/27 or 40.7% of all mutant chromosomes in ethnic Tatars. Surprisingly, the common Scandinavian mutation IVS12ntlg --> a was also present in Tataria, as was the delta agE221D222fs mutation found previously only in Denmark. Thus, some direct or indirect gene flow from Scandinavian into Tataria seems evident. Finally, the complete absence of PAH mutations previously observed in Oriental populations suggests that there was little gene flow into Tataria from Eastern Asia. PMID:8528673

  8. Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice.

    PubMed

    Sawin, Emily A; De Wolfe, Travis J; Aktas, Busra; Stroup, Bridget M; Murali, Sangita G; Steele, James L; Ney, Denise M

    2015-10-01

    Glycomacropeptide (GMP) is a 64-amino acid (AA) glycophosphopeptide with application to the nutritional management of phenylketonuria (PKU), obesity, and inflammatory bowel disease (IBD). GMP is a putative prebiotic based on extensive glycosylation with sialic acid, galactose, and galactosamine. Our objective was to determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations, short-chain fatty acids (SCFA), and immune responses. Weanling PKU (Pah(enu2)) and wild-type (WT) C57Bl/6 mice were fed isoenergetic AA, GMP, or casein diets for 8 wk. The cecal content and feces were collected for microbial DNA extraction to perform 16S microbiota analysis by Ion Torrent PGM sequencing. SCFA were determined by gas chromatography, plasma cytokines via a Bio-Plex Pro assay, and splenocyte T cell populations by flow cytometry. Changes in cecal and fecal microbiota are primarily diet dependent. The GMP diet resulted in a reduction from 30-35 to 7% in Proteobacteria, genera Desulfovibrio, in both WT and PKU mice with genotype-dependent changes in Bacteroidetes or Firmicutes. Cecal concentrations of the SCFA acetate, propionate, and butyrate were increased with GMP. The percentage of stimulated spleen cells producing interferon-γ (IFN-γ) was significantly reduced in mice fed GMP compared with casein. In summary, plasma concentrations of IFN-γ, TNF-α, IL-1β, and IL-2 were reduced in mice fed GMP. GMP is a prebiotic based on reduction in Desulfovibrio, increased SCFA, and lower indexes of inflammation compared with casein and AA diets in mice. Functional foods made with GMP may be beneficial in the management of PKU, obesity, and IBD. PMID:26251473

  9. Comparison of alpha-methylphenylalanine and p-chlorophenylalanine as inducers of chronic hyperphenylalaninaemia in developing rats.

    PubMed Central

    Delvalle, J A; Dienel, G; Greengard, O

    1978-01-01

    alpha-Methylphenylalanine is a very weak competitive inhibitor of rat liver phenylalanine hydroxylase in vitro but a potent suppressor in vivo. The loss of the hepatic activity (the renal one is unaffected) becomes maximal (70-75% decrease; cf. control) 18h after the administration (per 10g body wt.) of 24 mumol of alpha-methylphenylalanine with or without 52 mumol of phenylalanine. Chronic suppression of hepatic phenylalanine hydroxylase was obtained by injections of alpha-methylphenylalanine plus phenylalanine to suckling rats, and by their addition to the diet after weaning. A series of comparisons of the effects of this treatment, and one with p-chlorophenylalanine, was then carried out. In both cases there was a rise (1.3-2-fold) in phenylalanine-pyruvate amino-transferase activity (but no change in four other enzyme activities) in the liver; in brain there was a rise in phosphoserine phosphatase activity, but the total activity and subcellular distribution of nine enzymes revealed no other abnormalities in cerebral development. Striking increases in the concentration of plasma phenylalanine during 26 of the 31 experimental days (with a transient fall at 18-22 days) were maintained by treatment with both analogues plus phenylalanine. However, p-chlorophenylalanine-treated animals had a 30-60% mortality rate and 27-52% decrease in body weight. Developing rats treated with alpha-methylphenylalanine, showing no growth deficit or signs of toxicity (e.g. cataracts), appear to be a more suitable model for the human disease of phenylketonuria. Their phenylalanine concentrations exhibited at least 20-40-fold increase during 50% of each of the first 18 days of life, and 30-fold after weaning. PMID:148273

  10. [Technological challenges and strategies for developing low-protein/protein-free cereal foods for the dietotherapic treatment].

    PubMed

    Zannini, Emanuele

    2014-01-01

    Western countries are finding health care costs to be a continuously increasing financial burden in excess of previous budgetary allocations. Medical nutrition therapies (MNT) have proven to be an efficient cost minimising tool whilst concurrently improving the patient's quality of life. These MNTs are defined as specially processed or formulated foods that are used for the dietary management of patients. Among the medical foods, low-protein/protein-free (LP/PF) foods have been shown to improve the physical manifestation of metabolic disorders in patients with amino acid or protein-related diseases, such as Phenylketonuria, Tyrosinaemia type I, as well as chronic kidney, and coeliac. Most of the cereal-based LP/PF foods currently marketed are a blend of refined or chemically-based food ingredients with unpalatable frequently artificial flavours, having excessive sweetness to mask the chemical taste of ingredients (drug-like approach). However, the adoption of an alternative to convention, such as a food-like approach to developing medical foods, it is a surprisingly complex process. This is specifically true when the technological aspects of LP/PF foods and, in particular, protein-free cereal foods are considered. The primary processing issues arise while trying to replace gluten in baked cereal products. This represents a significant technological challenge, since gluten is an essential structural network-building protein necessary for baked goods. In this article, the suitable food technology challenges and strategies for developing LP/PF cereal foods able to overcome the significant limitations of a food-like approach will be addressed. PMID:24777928

  11. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement.

  12. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:26088792

  13. Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid

    PubMed Central

    Sanayama, Yoshitami; Matsumoto, Akio; Shimojo, Naoki; Kohno, Yoichi; Nakaya, Haruaki

    2014-01-01

    Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model. Here, we present a novel in vitro cellular model using K562-D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range, but not phenylpyruvate. The increased expression of the L-type amino acid transporter (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine over phenylalanine effectively restored cell proliferation, although other amino acids did not improve K562-D cell proliferation over phenylalanine. Biochemical analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal target of phenylalanine in K562-D cell proliferation, and supplementation of valine restored mTORC1 activity. Our results show that K562-D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease. PMID:25373594

  14. Estimation of carrier frequencies of six autosomal-recessive Mendelian disorders in the Korean population.

    PubMed

    Song, Min-Jung; Lee, Seung-Tae; Lee, Mi-Kyung; Ji, Yongick; Kim, Jong-Won; Ki, Chang-Seok

    2012-02-01

    Although many studies have been performed to identify mutations in Korean patients with various autosomal-recessive Mendelian disorders (AR-MDs), little is known about the carrier frequencies of AR-MDs in the Korean population. Twenty common mutations from six AR-MDs, including Wilson disease (WD), non-syndromic hearing loss (NSHL), glycogen storage disease type Ia (GSD Ia), phenylketonuria (PKU), congenital hypothyroidism (CH), and congenital lipoid adrenal hyperplasia (CLAH) were selected to screen for based on previous studies. A total of 3057 Koreans were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry followed by confirmation using the Sanger sequencing. We found 201 and 8 carriers with either one or two mutations in different genes, respectively, yielding a total carrier frequency of 1 in 15 (6.7%). Of the six AR-MDs, NSHL has the highest carrier frequency followed by WD, CH, CLAH, GSD Ia, and PKU. As carrier screening tests are becoming prevalent and the number of mutations known and tested is rising, a priori data on the carrier frequencies in different ethnic groups is mandatory to plan a population screening program and to estimate its efficiency. In light of this, the present results can be used as a basis to establish a screening policy for common AR-MRs in the Korean population. PMID:22170460

  15. Adolescent development

    MedlinePlus

    Development - adolescent; Growth and development - adolescent ... During adolescence, children develop the ability to: Understand abstract ideas. These include grasping higher math concepts, and developing moral ...

  16. A resolution designating December 3, 2013, as "National Phenylketonuria Awareness Day".

    THOMAS, 113th Congress

    Sen. Isakson, Johnny [R-GA

    2013-11-21

    11/21/2013 Referred to the Committee on the Judiciary. (text of measure as introduced: CR S8465) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  17. A resolution designating December 3, 2014, as "National Phenylketonuria Awareness Day".

    THOMAS, 113th Congress

    Sen. Isakson, Johnny [R-GA

    2014-11-20

    12/03/2014 Resolution agreed to in Senate without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  18. A resolution designating December 3, 2012, as "National Phenylketonuria Awareness Day".

    THOMAS, 112th Congress

    Sen. Isakson, Johnny [R-GA

    2012-09-19

    09/19/2012 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (consideration: CR S6469-6472; text as passed Senate: CR S6470; text of measure as introduced: CR S6465) (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  19. An Efficient Trio-Based Mini-Haplotyping Method for Genetic Diagnosis of Phenylketonuria

    PubMed Central

    Talebi, Saeed; Entezam, Mona; Mohajer, Neda; Kazemi-sefat, Golnaz-Ensieh; Razipour, Masoumeh; Ahmadloo, Somayeh; Setoodeh, Aria; Keramatipour, Mohammad

    2016-01-01

    Objective The phenylalanine hydroxylase (PAH) locus has high linkage disequilibrium. Haplotypes related to this locus may thus be considered sufficiently informative for genetic diagnosis and carrier screening using multi-allelic markers. In this study, we present an efficient method for haplotype analysis of PAH locus using multiplexing dyes. In addition, we explain how to resolve the dye shift challenge in multiplex short tandem repeat (STR) genotyping. Materials and Methods One hundred family trios were included in this descriptive study. The forward primer of a tetra-nucleotide STR and the reverse primer of a variable number tandem repeat (VNTR) were labeled with three different non-overlapping dyes 5-carboxyfluorescein (FAM), 6-carboxy-N,N,N’,N’-tetramethylrhodamine (HEX) and 6-carboxy-N,N,N’,N’-tetramethylrhodamine (TAMRA). The polymerase chain reaction (PCR) products from each family trio were multiplexed for capillary electrophoresis and results were analyzed using Peak Scanner software. Results Multiplexing trio products decreased the cost significantly. The TAMRA labeled products had a significant predictable shift (migrated at a slower electrophoretic rate) relative to the HEX and FAM labeled products. Through our methodology we achieve, the less inter-dye shift than intra-dye shift variance. Correcting the dye shift in the labeled products, according to the reference allele size, significantly decreased the inter-dye variability (P<0.001). Conclusion Multiplexing trio products helps to detect and resolve the dye shift accurately in each family, which otherwise would result in diagnostic error. The dye system of FAM, HEX and TAMRA is more feasible and cheaper than other dye systems. PMID:27540528

  20. A new amino acid mixture permits new approaches to the treatment of phenylketonuria.

    PubMed

    Buist, N R; Prince, A P; Huntington, K L; Tuerck, J M; Waggoner, D D

    1994-12-01

    A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance. PMID:7766965

  1. Screening Children with Autism for Fragile-X Syndrome and Phenylketonuria. Brief Report.

    ERIC Educational Resources Information Center

    Pueschel, Siegfried M.; And Others

    1985-01-01

    Family histories, comprehensive physical examinations, and chromosome analyses of 35 males with autism were performed. Results indicated that the fragile X syndrome may be present in less than 16 percent of persons whose family history or physical features suggest the condition's possible presence. Screening 42 autistic children for…

  2. An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand

    PubMed Central

    Thiboonboon, Kittiphong; Leelahavarong, Pattara; Wattanasirichaigoon, Duangrurdee; Vatanavicharn, Nithiwat; Wasant, Pornswan; Shotelersuk, Vorasuk; Pangkanon, Suthipong; Kuptanon, Chulaluck; Chaisomchit, Sumonta; Teerawattananon, Yot

    2015-01-01

    Background Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. Method A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality-adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. Results The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. Conclusion At the current ceiling threshold, neonatal screening using MS

  3. Web-Based Newborn Screening System for Metabolic Diseases: Machine Learning Versus Clinicians

    PubMed Central

    Chen, Wei-Hsin; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

    2013-01-01

    Background A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. Objective The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. Methods The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets

  4. Child Development

    MedlinePlus

    ... content Start of Search Controls Search Form Controls Child Development Cancel Submit Search The CDC CDC A-Z ... Z # Start of Search Controls Search Form Controls Child Development Cancel Submit Search The CDC Child Development Note: ...

  5. Adolescent development

    MedlinePlus

    Development - adolescent; Growth and development - adolescent ... rights and privileges. Establish and maintain satisfying relationships. Adolescents will learn to share intimacy without feeling worried ...

  6. Child Development

    MedlinePlus

    As children grow older, they develop in several different ways. Child development includes physical, intellectual, social, and emotional changes. Children grow and mature at very different rates. It's ...

  7. Consumerism & Development.

    ERIC Educational Resources Information Center

    Ockenden, Sandy

    1991-01-01

    This material asks social studies students in Canada to recognize the implications of the lifestyles of citizens in developed countries, and the power that consumers have to create change for a better world, to be agents of positive development. Development is seen as a four faceted process. This model implies that development is an approach to…

  8. Fetal development

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002398.htm Fetal development To use the sharing features on this page, ... Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et ...

  9. Toddler Development

    MedlinePlus

    ... developmental milestones. It is exciting to watch your toddler learn new skills. The normal development of children ... playing with others, taking turns, doing fantasy play Toddlers do not develop at the same rate. There ...

  10. Technology Development.

    ERIC Educational Resources Information Center

    Gomory, Ralph E.

    1983-01-01

    The evolutionary character and complexity of technological development is discussed, focusing on the steam engine and computer as examples. Additional topics include characteristics of science/technology, cultural factors in technological development, technology transfer, and problems in technological organization. (JN)

  11. Toddler development

    MedlinePlus

    Toddlers are children ages 1 - 3. CHILD DEVELOPMENT THEORIES Cognitive (thought) development skills typical for toddlers include: Early use of instruments or tools Following visual (then later, invisible) displacement (moving ...

  12. Child Development

    MedlinePlus

    ... grow older, they develop in several different ways. Child development includes physical, intellectual, social, and emotional changes. ... same sex. Peer approval becomes very important. Your child may try new behaviors to be part of " ...

  13. Sustainable Development.

    ERIC Educational Resources Information Center

    Auerbach, Raymond

    1994-01-01

    Discusses South African national development priorities, sustainable development, and the future of agriculture and presents three scenarios of possible national action: production for sale and export, household food security, and conservation of natural resources. (MKR)

  14. Developer Network

    Energy Science and Technology Software Center (ESTSC)

    2012-08-21

    NREL's Developer Network, developer.nrel.gov, provides data that users can access to provide data to their own analyses, mobile and web applications. Developers can retrieve the data through a Web services API (application programming interface). The Developer Network handles overhead of serving up web services such as key management, authentication, analytics, reporting, documentation standards, and throttling in a common architecture, while allowing web services and APIs to be maintained and managed independently.

  15. Teacher Development.

    ERIC Educational Resources Information Center

    1997

    Eight conference papers on language teacher development are presented, including: "Mosaics of Teacher Development and Socialization" (Andrew Barfield, Paul A. Beaufait, Sean Conley, Tim Murphey, Katsura Haruko), a panel presentation on aspects of and experiments in teacher development; "Questions About Teaching? Answers from Teachers!" (David…

  16. Career Development.

    ERIC Educational Resources Information Center

    1996

    This document consists of four papers presented during a symposium on career development moderated by David Bjorkquist at the 1996 conference of the Academy of Human Resource Development (AHRD). "A Mentoring Model for Career Development" (Mary Finnegan) describes a study that created a model based on the assumption that mentoring is an essential…

  17. Faculty Development.

    ERIC Educational Resources Information Center

    Gillan, Bob, Ed.; McFerrin, Karen, Ed.

    This document contains the following papers on faculty development and technology: "Involving Faculty in Faculty Development" (Kristine Blair and Dan Madigan); "Technology Use in Higher Education: A Faculty Development Model" (Jessica Kahn); "A Faculty of Education as a Community of Learners: Growing to Meet the Demands of Instruction and…

  18. MedlinePlus: Newborn Screening

    MedlinePlus

    ... Phenylketonuria National Institutes of Health The primary NIH organization for research on Newborn Screening is the National Institute of Child Health and Human Development Languages Arabic (العربية) Bosnian (Bosanski) Chinese - Simplified (简体中文) ...

  19. Neurovascular development

    PubMed Central

    James, Jennifer M

    2009-01-01

    Neurovascular development in the central nervous system has a rich history and compelling significance. The developing central nervous system (CNS) does not produce vascular progenitor cells, and so ingression of blood vessels is required for continued CNS development and function. Classic studies provide elegant descriptions of formation of the vascular plexus that surrounds the embryonic brain and spinal cord, and the subsequent ingression of blood vessels into the neural tissue. Recent work has focused on the molecular pathways responsible for neurovascular cross-talk and development of the blood-brain barrier. Here we review neurovascular development in the central nervous system, with emphasis on the spinal cord. We discuss the historical work, the current status of our knowledge and unanswered questions. The importance of neurovascular development to diseases of the cerebral vasculature and the neural stem cell niche are discussed. PMID:19363295

  20. Program Development

    SciTech Connect

    Atencio, Julian J.

    2014-05-01

    This presentation covers how to go about developing a human reliability program. In particular, it touches on conceptual thinking, raising awareness in an organization, the actions that go into developing a plan. It emphasizes evaluating all positions, eliminating positions from the pool due to mitigating factors, and keeping the process transparent. It lists components of the process and objectives in process development. It also touches on the role of leadership and the necessity for audit.

  1. KENO developments

    SciTech Connect

    Hollenbach, D.F.; Landers, N.F.; Petrie, L.M.

    1997-06-01

    Modifications and developments to the series of KENO multigroup, criticality safety transport codes are very briefly summarized. Three areas are addressed: (1) modifications to KENO-V.a, (2) development of KENO-VI, (3) modifications to the CSAS4 sequence of the SCALE package, and (4) future work on KENO related programs. Minor changes have been made to KENO-V.a, primarily for maintenance. KENO-VI has been developed and will be released soon. A new search type is being developed in SCALE to allow CSAS4 to do a concentration search on a mixture component.

  2. Developable resources

    SciTech Connect

    Hunt, R.T.; Hunt, J.M.

    1995-01-01

    In the United States, it has become the conventional wisdom that all developable conventional hydropower resources have been exhausted. Studies by the US Department of Energy (DOE) and other agencies find differently. The root of disagreement may lie in the definition of what is developable. Environmental special interest groups now define developable hydropower sites as those having zero effect on the environment. As a result they conclude there are no additional developable hydropower sites. By contrast, the definition used by DOE and others is broader as it balances economic, technical, and environmental factors in accordance with the Federal Power Act.

  3. Mutation analysis of the phenylalanine hydroxylase gene in Azerbaijani population, a report from West Azerbaijan province of Iran

    PubMed Central

    Bagheri, Morteza; Rad, Isa Abdi; Jazani, Nima Hosseini; Zarrin, Rasoul; Ghazavi, Ahad

    2015-01-01

    Objective(s): Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. The present study was carried out for mutation analysis of the PAH gene in West Azerbaijan province of Iran. Materials and Methods: A total of 218 alleles from 40 PKU families were studied using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. Results: The frequencies of IVS10-11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in cases group, and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples. Conclusion: It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population. To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran. PMID:26351554

  4. Categorizing genetic tests to identify their ethical, legal, and social implications.

    PubMed

    Burke, W; Pinsky, L E; Press, N A

    2001-01-01

    Practice standards in medical genetics provide an implicit guide to the ethical, legal, and social implications (ELSI) of genetic tests. The common use of nondirective counseling reflects the principle that many testing decisions should be determined by personal values. Yet geneticists make test recommendations in some circumstances, e.g., RET mutation testing for MEN2 and newborn screening for phenylketonuria (PKU). Conversely, many geneticists recommend against testing for Apolipoprotein E (ApoE) alleles to predict Alzheimer disease (AD) risk. Taken together, these examples suggest that genetic tests can be categorized by a joint consideration of clinical validity and availability of effective treatment for persons who test positive. For genetic tests with high clinical validity/no treatment (e.g., presymptomatic testing for Huntington disease), the predominant concern is adequate nondirective counseling to ensure an informed, autonomous decision. By contrast, the predominant concern for tests with high clinical validity/effective treatment (e.g., PKU) is assuring access to care for eligible persons. For tests with limited clinical validity/no treatment (e.g., ApoE), recommending against test use can be justified on the principle of avoiding harm. For a fourth category, tests with limited clinical validity/effective treatment (e.g., HFE mutation testing for hereditary hemochromatosis), net benefit is the issue: the balance between potential benefits of treatment and potential harms of genetic labeling must be weighed. Where uncertainty exists concerning both clinical validity and effectiveness of treatment, as in the case of BRCA 1/2 mutation testing, the value of testing may vary according to different testing contexts. This approach to test categorization allows a rapid determination of the predominant ELSI concerns for different kinds of genetic tests and identifies the data most urgently needed for test evaluation. PMID:11778984

  5. Collection Development.

    ERIC Educational Resources Information Center

    School Libraries in Canada, 2002

    2002-01-01

    Includes 21 articles that discuss collection development in Canadian school libraries. Topics include digital collections in school library media centers; print and electronic library resources; library collections; collaborative projects; print-disabled students; informing administrators of the importance of collection development; censorship;…

  6. Management Development.

    ERIC Educational Resources Information Center

    1997

    This document contains three papers from a symposium on management development. "LMX (Leader-Member Exchange) Theory, Personality Type, and Management Development" (Janet Z. Burns) reports the results of a study on the similarities and differences in personality type (as outlined in the theories of Carl Jung and Isabel Myers) and its relationship…

  7. Numerical Development

    ERIC Educational Resources Information Center

    Siegler, Robert S.; Braithwaite, David W.

    2016-01-01

    In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

  8. Staff Development.

    ERIC Educational Resources Information Center

    Reusswig, James, Ed.; Ponzio, Richard, Ed.

    1980-01-01

    Eight essays are presented which reflect current problems, issues, and practices related to the development of teacher and administrator expertise. The authors are school district and public school administrators, faculty of schools of education, and a director of staff development in a state department of education. The topics treated are: (1)…

  9. Professional Development.

    ERIC Educational Resources Information Center

    Benson, Chris, Ed.

    2000-01-01

    This serial issue contains 12 articles on the theme of "Professional Development," specifically about how teachers in the Bread Loaf Rural Teacher Network (BLRTN) are fostering their own and each other's development as teachers. The BLRTN consists of approximately 260 rural teachers in Alaska, Arizona, Colorado, Georgia, Kentucky, Mississippi, New…

  10. [Toddler Development.

    ERIC Educational Resources Information Center

    Pawl, Jeree, Ed.

    1991-01-01

    This theme newsletter issue presents seven articles describing toddler behavior and development, services for toddlers, and toddlers with special needs. The first article, "Toddlers: Themes and Variations" (Lois Barclay Murphy and Colleen Small) focuses on variations in toddler development, noting emerging skills, language, and the caregiver role.…

  11. Technology development.

    PubMed

    Gomory, R E

    1983-05-01

    In technology development significant advances are as often the result of a series of evolutionary steps as they are of breakthroughs. This is illustrated by the examples of the steam engine and the computer. Breakthroughs, such as the transistor, are relatively rare, and are often the result of the introduction of new knowledge coming from a quite different area. Technology development is often difficult to predict because of its complexity; practical considerations may far outweigh apparent scientific advantages, and cultural factors enter in at many levels. In a large technological organization problems exist in bringing scientific knowledge to bear on development, but much can be done to obviate these difficulties. PMID:17749515

  12. Sustainable developments

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    Hundreds of diplomats, along with industry, finance, environment, and labor leaders from around the world met from April 20 to May 1 for the sixth session of the United Nations Commission for Sustainable Development (CSD), an annual follow-up conference to track the Agenda 21 program of action adopted at the 1992 Rio de Janeiro Earth Summit.During the session, which focused on freshwater management concerns and the role of industry in sustainable development, the participants discussed a number of issues about development and parity among northern and southern hemisphere countries.

  13. Eye development.

    PubMed

    Baker, Nicholas E; Li, Ke; Quiquand, Manon; Ruggiero, Robert; Wang, Lan-Hsin

    2014-06-15

    The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This article provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens. PMID:24784530

  14. Toddler Development

    MedlinePlus

    ... is exciting to watch your toddler learn new skills. The normal development of children aged 1-3 can be broken down into the following areas: Gross motor - walking, running, climbing Fine motor - feeding themselves, drawing Sensory - seeing, hearing, tasting, ...

  15. Brain Development

    MedlinePlus

    ... new neural connections every second. This growing brain development is influenced by many factors, including a child’s relationships, experiences and environment. Learn more about the crucial role you play ...

  16. EYE DEVELOPMENT

    PubMed Central

    Baker, Nicholas E.; Li, Ke; Quiquand, Manon; Ruggiero, Robert; Wang, Lan-Hsin

    2014-01-01

    The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This chapter provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens. PMID:24784530

  17. Speech Development

    MedlinePlus

    ... W View More… Donate Donor Spotlight Fundraising Ideas Vehicle Donation Volunteer Efforts Speech Development skip to submenu ... Lip and Palate . Bzoch (1997). Cleft Palate Speech Management: A Multidisciplinary Approach . Shprintzen, Bardach (1995). Cleft Palate: ...

  18. Leaf Development

    PubMed Central

    2013-01-01

    Leaves are the most important organs for plants. Without leaves, plants cannot capture light energy or synthesize organic compounds via photosynthesis. Without leaves, plants would be unable perceive diverse environmental conditions, particularly those relating to light quality/quantity. Without leaves, plants would not be able to flower because all floral organs are modified leaves. Arabidopsis thaliana is a good model system for analyzing mechanisms of eudicotyledonous, simple-leaf development. The first section of this review provides a brief history of studies on development in Arabidopsis leaves. This history largely coincides with a general history of advancement in understanding of the genetic mechanisms operating during simple-leaf development in angiosperms. In the second section, I outline events in Arabidopsis leaf development, with emphasis on genetic controls. Current knowledge of six important components in these developmental events is summarized in detail, followed by concluding remarks and perspectives. PMID:23864837

  19. Teen Development

    MedlinePlus

    ... 12 and 16 for boys. As your body changes, you may have questions about sexual health. During this time, you start to develop your own unique personality and opinions. Some changes that you might notice include Increased independence from ...

  20. Development risks

    SciTech Connect

    Riedy, M.; Desai, S.

    1996-04-01

    Risks associated with hydropower production development in India are discussed in this article. A project prospectus for the development of India`s estimated 84,044 MW(e) hydropower potential is given which accounts for environmental and regulatory concerns. Regulations issued by the Government of Industry regarding private investment in hydropower are outlined, and additional policies which are expected to be instituted are discussed.

  1. Sustainable development is healthy development.

    PubMed

    Litsios, S

    1994-01-01

    Economic growth has brought with it substantial environmental damage. Nature has been abused and little consideration has been given to the consequences, among them the adverse effects on health. Healthy people are vital for local development that is both economically and ecologically sound. The health sector should be actively involved in the movement for sustainable development. What this would require in practice is considered below, with particular reference to the quality of life in regions of tropical forest. PMID:8018295

  2. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  3. Sustainable Development

    NASA Astrophysics Data System (ADS)

    Schmandt, Jurgen; Ward, C. H.; Marilu Hastings, Assisted By

    2000-04-01

    Demographers predict that the world population will double during the first half of the 21st century before it will begin to level off. In this volume, a group of prominent authors examine what societal changes must occur to meet this challenge to the natural environment and the transformational changes that we must experience to achieve sustainability. Frances Cairncross, Herman E. Daly, Stephen H. Schneider and others provide a broad discussion of sustainable development. They detail economic and environmental, as well as spiritual and religious, corporate and social, scientific and political factors. Sustainable Development: The Challenge of Transition offers many insightful policy recommendations about how business, government, and individuals must change their current values, priorities, and behavior to meet present and future challenges. It will appeal to scholars and decision makers interested in global change, environmental policy, population growth, and sustainable development, and also to corporate environmental managers.

  4. Defining "Development".

    PubMed

    Pradeu, Thomas; Laplane, Lucie; Prévot, Karine; Hoquet, Thierry; Reynaud, Valentine; Fusco, Giuseppe; Minelli, Alessandro; Orgogozo, Virginie; Vervoort, Michel

    2016-01-01

    Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory. PMID:26969977

  5. Algorithm development

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.; Lomax, Harvard

    1987-01-01

    The past decade has seen considerable activity in algorithm development for the Navier-Stokes equations. This has resulted in a wide variety of useful new techniques. Some examples for the numerical solution of the Navier-Stokes equations are presented, divided into two parts. One is devoted to the incompressible Navier-Stokes equations, and the other to the compressible form.

  6. Interorganizational Development.

    ERIC Educational Resources Information Center

    Schermerhorn, John R., Jr.

    1979-01-01

    Interorganizational development is the application of social science knowledge to the creation of planned, systematic and mutually beneficial cooperative relationships between otherwise autonomous organizations. This paper introduces the concept as a means of focusing attention on key action and research issues associated with interorganizational…

  7. Gender Development.

    ERIC Educational Resources Information Center

    Golombok, Susan; Fivush, Robyn

    In spite of the loosening ties between reproductive and social roles, the worlds of men and women and boys and girls, are clearly not the same. There is much more to being female or male than the potential to mother or father a child. Gender development does not simply depend on children's relationship with their parents: it results from a complex…

  8. Workforce Development.

    ERIC Educational Resources Information Center

    1999

    This document contains four symposium papers on work force development. "Effects of Two Different Learning Paths on School-to-Work Transition" (Esther Van Der Schoot) discusses a Dutch study documenting that the following items make a difference in the school-to-work transition: learning path, curriculum characteristics, individual…

  9. Contraceptive Development.

    ERIC Educational Resources Information Center

    Troen, Philip; And Others

    This report provides an overview of research activities and needs in the area of contraceptive development. In a review of the present state, discussions are offered on the effectiveness and drawbacks of oral contraceptives, intrauterine devices, barrier methods, natural family planning, and sterilization. Methods of contraception that are in the…

  10. Developing ADHD

    ERIC Educational Resources Information Center

    Taylor, Eric

    2009-01-01

    Over the past 50 years the concept of attention deficit/hyperactivity disorder (ADHD) has developed from the notion of a specific form of brain dysfunction to that of a heterogeneous set of related behaviours. The great advances in genetics, neuroimaging and neuropsychiatry have made it one of the best understood forms of complex mental…

  11. Gender Development

    ERIC Educational Resources Information Center

    Owen Blakemore, Judith E.; Berenbaum, Sheri A.; Liben, Lynn S.

    2008-01-01

    This new text offers a unique developmental focus on gender. Gender development is examined from infancy through adolescence, integrating biological, socialization, and cognitive perspectives. The book's current empirical focus is complemented by a lively and readable style that includes anecdotes about children's everyday experiences. The book's…

  12. New Developments

    ERIC Educational Resources Information Center

    Lohmander, Maelis Karlsson, Ed.; Rabusicova, Milada; Einarsdottir, Johanna

    2008-01-01

    The development of early childhood education (ECE) in Europe and beyond is inextricably linked with women's roles and power in society. Towards the end of the nineteenth and beginning of the twentieth century in a context of urbanisation and industrialisation the need for some sort of public childcare became apparent in many countries. Whereas…

  13. Trends Developments.

    ERIC Educational Resources Information Center

    ASPBAE Courier Service, 1981

    1981-01-01

    This issue contains extracts from twenty-one country reports and case studies presented to the Unesco Regional Seminar on Adult Education and Development in Bangkok, November 24-December 4, 1980. The excerpts have an emphasis on innovations in adult education in the region. Countries and programs discussed include (1) community…

  14. CAREER DEVELOPMENT

    EPA Science Inventory

    The Baltimore Summit Project on Career Development/PERFORMS Enhancement/360 Evaluations for All has made some progress. We have identified the fact that we cannot change the current Pass/Fail PERFORMS system to a tiered system. The current pass/fail system does not have a mechani...

  15. Envisioning Development

    ERIC Educational Resources Information Center

    Dealtry, Richard

    2004-01-01

    This paper focuses on an important innovative development in new generation corporate university management. It addresses the thematic area of visual learning that is captured in the term "The Art of Minds-eye Management". It reflects upon experiences with groups of managers in enhancing perceptive competencies using visual awareness learning…

  16. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  17. Fetal development

    MedlinePlus

    Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et al, eds. Williams Obstetrics . 23rd ed. New York, NY: McGraw-Hill; ... and fetal physiology. In: Gabbe SG, Niebyl JR, Simpson JL, ...

  18. Flower Development

    PubMed Central

    Alvarez-Buylla, Elena R.; Benítez, Mariana; Corvera-Poiré, Adriana; Chaos Cador, Álvaro; de Folter, Stefan; Gamboa de Buen, Alicia; Garay-Arroyo, Adriana; García-Ponce, Berenice; Jaimes-Miranda, Fabiola; Pérez-Ruiz, Rigoberto V.; Piñeyro-Nelson, Alma; Sánchez-Corrales, Yara E.

    2010-01-01

    Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID:22303253

  19. New Developments

    ERIC Educational Resources Information Center

    Lohmander, Maelis Karlson; Vandenbroeck, Michel; Pirard, Florence; Peeters, Jan; Alvestad, Marit

    2009-01-01

    New developments and challenges regarding early childhood education (ECE) policy and practice in Norway and in the Flemish and French communities in Belgium are presented in this issue. There are clear differences between the countries when comparing systems they have chosen for ECE. In Belgium, supervision and responsibilities for education,…

  20. Professional Development.

    ERIC Educational Resources Information Center

    Inouye, Patricia C.; And Others

    A Liaison Committee at the University of California-Davis' library studied the concept of professional development, including the individual librarian's responsibility and the General Library's role in assisting its librarians. This document enumerates the committee's recommendations and outlines (1) the factors which influence the extent of a…

  1. Oh, Develop

    NASA Technical Reports Server (NTRS)

    Post, Todd

    2003-01-01

    In a mature view of the subject, career development is not simply four years of college or a week at training, culminating in a diploma or a certificate to hang on an office wall. That's why we wanted to take a broad look at career development in this issue of ASK. Take for example, Dr. Gerald Mulenburg s contribution, Fly on the Wall. When Mulenburg and other members of a knowledge-sharing group at Ames were invited to observe an upcoming project review, Mulenburg thought it would be interesting to learn how another project does its reviews. Note that Mulenburg is no fresh out who's never attended a NASA project review. Not only has he been through a fair share of them as the reviewed, he has also been on the other side of the table as a reviewer. This experienced project manager recognizes that at any stage of a career there is room to grow and develop one's repertoire. Too often people associate career development with textbooks and role classroom training, far removed from project life. But classroom training need not be like this, as you'll find in our Special Feature, The Enterprise Project by Wendy Dolci, which sprung out of an APPL Advanced Project Management class in July 2003 at Ames Research Center. In addition to Dolci, some of her classmates contribute to the story. Mike Sander of the Jet Propulsion Laboratory, project manager for the Mars Science Laboratory mission, who provided the assignment on which the story is based, also has a cameo in the story. We think Dolci's story is an inspiring example of what classroom training can be if it's approached imaginatively and made to serve a practical purpose. Another story from Ames, by Frank Larsen, takes a different twist on career development. At the annual Experimental Aircraft Association Fly-in in Oshkosh, Wisconsin, Larsen represented Ames at a NASA booth. While there, Larsen met a colleague from Glenn Research Center. Months later on a project with a quick turnaround, he remembered his colleague from

  2. Adaptive Development

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The goal of this research is to develop and demonstrate innovative adaptive seal technologies that can lead to dramatic improvements in engine performance, life, range, and emissions, and enhance operability for next generation gas turbine engines. This work is concentrated on the development of self-adaptive clearance control systems for gas turbine engines. Researchers have targeted the high-pressure turbine (HPT) blade tip seal location for following reasons: Current active clearance control (ACC) systems (e.g., thermal case-cooling schemes) cannot respond to blade tip clearance changes due to mechanical, thermal, and aerodynamic loads. As such they are prone to wear due to the required tight running clearances during operation. Blade tip seal wear (increased clearances) reduces engine efficiency, performance, and service life. Adaptive sealing technology research has inherent impact on all envisioned 21st century propulsion systems (e.g. distributed vectored, hybrid and electric drive propulsion concepts).

  3. Polarization developments

    SciTech Connect

    Prescott, C.Y.

    1993-07-01

    Recent developments in laser-driven photoemission sources of polarized electrons have made prospects for highly polarized electron beams in a future linear collider very promising. This talk discusses the experiences with the SLC polarized electron source, the recent progress with research into gallium arsenide and strained gallium arsenide as a photocathode material, and the suitability of these cathode materials for a future linear collider based on the parameters of the several linear collider designs that exist.

  4. Illuminating Development

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Through the support of the NASA SBIR program, Control Vision, Inc. developed novel video techniques for clear, high resolution, real-time imaging of high temperature, high-energy industrial processes, such as welding, plasma arc spraying (coating), arc furnaces, metal casting and refractories (ceramics) melting. The Control Vision systems use reflected laser or strobe illumination, combined with ultra-short exposure times to create video, including the allowance of particle imaging velocimetry (PIV) of fast moving powder particles buried within a plasma stream.

  5. Yardang Development

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    Released 16 July 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth.

    Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms.

    This image illustrates different amounts of yardang development on the large deposit found on the floor of Nicholson Crater. Note the formation of the ridge/trough shape at the bottom part of the main deposit.

    Image information: VIS instrument. Latitude 0.2, Longitude 195.3 East (164.7 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for

  6. Professional development

    NASA Astrophysics Data System (ADS)

    Yoon, Jin Hee; Hartline, Beverly Karplus; Milner-Bolotin, Marina

    2013-03-01

    The three sessions of the professional development workshop series were each designed for a different audience. The purpose of the first session was to help mid-career physicists aspire for and achieve leadership roles. The second session brought together students, postdoctoral fellows, and early-career physicists to help them plan their career goals and navigate the steps important to launching a successful career. The final session sought to increase awareness of the results of physics education research, and how to use them to help students-especially women-learn physics better. The presentations and discussions were valuable for both female and male physicists.

  7. Recall rate and positive predictive value of MSUD screening is not influenced by hydroxyproline.

    PubMed

    Fingerhut, Ralph

    2009-05-01

    Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder caused by the deficiency of the branched-chain 2-oxo acid dehydrogenase (BCOA-DH) complex. The worldwide incidence is approximately 1 in 185,000. MSUD is integrated in many "expanded" newborn screening (NBS) programs that use electrospray ionization tandem mass spectrometry (ESI-MS/MS). Elevated leucine, isoleucine, and alloisoleucine in the dried blood samples (DBS) of newborns are diagnostic parameters. However, with the applied method, it is not possible to distinguish the amino acids from each other, and also not from the other isobaric amino acid, hydroxyproline. While the branched chain amino acids (BCAA) leucine, isoleucine, and alloisoleucine are no diagnostic problem, because they are all elevated in MSUD patients, and, rather, increase the diagnostic sensitivity and specificity, hydroxyproline may cause false-positive screening results. Hydroxyproline is elevated in the benign familial condition hyperhydroxyprolinemia, which needs no medical intervention. The detection of cases with hyperhydroxyprolinemia have formerly been reported from screening programs that used thin-layer chromatography for phenylketonuria (PKU) screening, and, recently, two more cases have been reported, detected by ESI-MS/MS-based NBS. However, the detection of non-diseases is a heavy burden for screening programs and should be avoided if possible. With optimal settings for the quantitation of BCAAs and interpretation rules, elevated hydroxyproline should not cause false-positive screening results. PMID:18682982

  8. Construction and evaluation of a novel bifunctional phenylalanine-formate dehydrogenase fusion protein for bienzyme system with cofactor regeneration.

    PubMed

    Jiang, Wei; Fang, Bai-Shan

    2016-05-01

    Phenylalanine dehydrogenase (PheDH) plays an important role in enzymatic synthesis of L-phenylalanine for aspartame (sweetener) and detection of phenylketonuria (PKU), suggesting that it is important to obtain a PheDH with excellent characteristics. Gene fusion of PheDH and formate dehydrogenase (FDH) was constructed to form bifunctional multi-enzymes for bioconversion of L-phenylalanine coupled with coenzyme regeneration. Comparing with the PheDH monomer from Microbacterium sp., the bifunctional PheDH-FDH showed noteworthy stability under weakly acidic and alkaline conditions (pH 6.5-9.0). The bifunctional enzyme can produce 153.9 mM L-phenylalanine with remarkable performance of enantiomers choice by enzymatic conversion with high molecular conversion rate (99.87 %) in catalyzing phenylpyruvic acid to L-phenylalanine being 1.50-fold higher than that of the separate expression system. The results indicated the potential application of the PheDH and PheDH-FDH with coenzyme regeneration for phenylpyruvic acid analysis and L-phenylalanine biosynthesis in medical diagnosis and pharmaceutical field. PMID:26819086

  9. The knowledge gap in expanded newborn screening: survey results from paediatricians in Massachusetts.

    PubMed

    Gennaccaro, M; Waisbren, S E; Marsden, D

    2005-01-01

    Massachusetts currently offers an optional expanded newborn screening programme that tests for 20 biochemical genetic disorders in addition to the mandated newborn screening tests, including phenylketonuria (PKU) and nine other biochemical genetic disorders. We conducted a mail survey of 550 paediatricians listed in the 2000 Massachusetts Healthcare Directory to determine paediatricians' preparedness in discussing expanded newborn screening and its results with families, and to determine in what specific format physicians in Massachusetts would prefer to receive educational materials and updates. Of surveys mailed, 35% (190/550) were returned within the allotted 3 weeks: 25 paediatricians (14%) were unaware of expanded newborn screening; 78 respondents (42%) indicated feeling less than prepared talking about test results with families; 100 paediatricians (54%) indicated a lack of information about metabolic disorders; 134 (73%) preferred information sent in postal mailings, 62 (34%) preferred grand rounds, 60 (33%) preferred educational seminars, and 58 (32%) preferred websites. Other formats receiving preferences of less than 30% included e-mail (27%), phone calls (8%), video (6%), and distance learning (1%). Paediatricians are ill-prepared for expanded newborn screening for biochemical genetic disorders. To address this problem, paediatricians in Massachusetts indicated a preference for unsolicited periodic mailings including short reviews and brochures. PMID:16435173

  10. Nozzle development

    SciTech Connect

    Dodge, F.T.; Dodge, L.G.; Johnson, J.E.

    1989-06-01

    The objective of this program has been the development of experimental techniques and data processing procedures to allow for the characterization of multi-phase fuel nozzles using laboratory tests. Test results were to be used to produce a single value coefficient-of-performance that would predict the performance of the fuel nozzles independent of system application. Several different types of fuel nozzles capable of handling multi-phase fuels have been characterized for: (a) fuel flow rate versus delivery pressure, (b) fuel-air ratio throughout the fuel spray or plume and the effective cone angle of the injector, and (c) fuel drop- or particle-size distribution as a function of fluid properties. Fuel nozzles which have been characterized on both single-phase liquids and multi-phase liquid-solid slurries include a variable-film-thickness nozzle, a commercial coal-water slurry (CWS) nozzle, and four diesel injectors of different geometries (tested on single-phase fluids only). Multi-phase mixtures includes CWS with various coal loadings, surfactant concentrations, and stabilizer concentrations, as well as glass-bead water slurries with stabilizing additives. Single-phase fluids included glycerol-water mixtures to vary the viscosity over a range of 1 to 1500 cP, and alcohol-water mixtures to vary the surface tension from about 22 to 73 dyne/cm. In addition, tests were performed to characterize straight-tube gas-solid nozzles using two differences size distributions of glass beads in air. Standardized procedures have been developed for processing measurements of spray drop-size characteristics and the overall cross-section average drop or particle size. 43 refs., 60 figs., 7 tabs.

  11. Sampling Development

    PubMed Central

    Adolph, Karen E.; Robinson, Scott R.

    2011-01-01

    Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of the enterprise. This article discusses how to sample development in order to accurately discern the shape of developmental change. The ideal solution is daunting: to summarize behavior over 24-hour intervals and collect daily samples over the critical periods of change. We discuss the magnitude of errors due to undersampling, and the risks associated with oversampling. When daily sampling is not feasible, we offer suggestions for sampling methods that can provide preliminary reference points and provisional sketches of the general shape of a developmental trajectory. Denser sampling then can be applied strategically during periods of enhanced variability, inflections in the rate of developmental change, or in relation to key events or processes that may affect the course of change. Despite the challenges of dense repeated sampling, researchers must take seriously the problem of sampling on a developmental time scale if we are to know the true shape of developmental change. PMID:22140355

  12. Sustainable Development: The Challenge for Community Development.

    ERIC Educational Resources Information Center

    Gamble, Dorothy N.; Weil, Marie O.

    1997-01-01

    Five areas of inquiry shape the sustainable development movement: environmental movement, women's movement, overpopulation concerns, critique of development models, and new indicators of social progress. Community development workers are challenged to prepare local development projects within a sustainable development framework. (SK)

  13. VAP Development: Initiation, Development, Evaluation, and Release

    SciTech Connect

    Jensen, M; Collis, Fast, J; Flynn, C; Mather, J; McFarlane, S; Monroe, J; Sivaraman, C; Xie, S

    2011-02-23

    This white paper provides a plan to formalize the evaluation of newly developed VAPs and a framework for the development of value-added products through four different stages: Initiation, Development, Evaluation, and Release.

  14. Developed-developing country partnerships: Benefits to developed countries?

    PubMed Central

    2012-01-01

    Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  15. Developed-developing country partnerships: benefits to developed countries?

    PubMed

    Syed, Shamsuzzoha B; Dadwal, Viva; Rutter, Paul; Storr, Julie; Hightower, Joyce D; Gooden, Rachel; Carlet, Jean; Bagheri Nejad, Sepideh; Kelley, Edward T; Donaldson, Liam; Pittet, Didier

    2012-01-01

    Developing countries can generate effective solutions for today's global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed--this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  16. Entrepreneurial Intentions in Developing and Developed Countries

    ERIC Educational Resources Information Center

    Iakovleva, Tatiana; Kolvereid, Lars; Stephan, Ute

    2011-01-01

    Purpose: This study proposes to use the Theory of Planned Behaviour to predict entrepreneurial intentions among students in five developing and nine developed countries. The purpose is to investigate whether entrepreneurial intention and its antecedents differ between developing and developed countries, and to test the theory in the two groups of…

  17. App Development Paradigms for Instructional Developers

    ERIC Educational Resources Information Center

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

  18. What Is Development?

    ERIC Educational Resources Information Center

    Astle, Alec

    1989-01-01

    Reviews inequalities in development, a topic in the New Zealand Form Six Geography Syllabus. Explains the different perspectives from which to approach development: academic, ideological, political, or personal. Considers the various meanings of development to less developed countries. (GG)

  19. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  20. Developing New Academic Developers: Doing before Being?

    ERIC Educational Resources Information Center

    Kensington-Miller, Barbara; Brailsford, Ian; Gossman, Peter

    2012-01-01

    A small group of new academic developers reflected on their induction into the profession and wondered if things could have been done differently. The researchers decided to question the directors of three tertiary academic development units about how they recruited new developers, what skills and competences they looked for and how they inducted…

  1. Improving spatial representation of soil moisture by integration of microwave observations and the temperature-vegetation-drought index derived from MODIS products

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Ling, Ziwei; Wang, Yang; Zeng, Hui

    2016-03-01

    The microwave observations of land surface soil moisture have been widely used for studying environmental change at large spatial scales. However, the coarse spatial resolution of the products limits their local-scale applications. In this paper, we developed a new method, which integrates the coarse spatial resolution soil moisture derived from microwave sensors and the temperature-vegetation-drought-index (TVDI) derived from the Moderate-resolution Imaging Spectroradiometer (MODIS) products, to spatially downscale soil moisture data from 25-km resolution to 1-km resolution. First, we assessed the quality of the remotely sensed soil moisture by comparing their values with field measured soil moisture at three temporal scales and two spatial scales. Second, we analyzed the robustness of the developed approach namely the PKU method by comparing its performance with the results of three published methods (i.e., the triangle-based method, the Merlin method, and the UCLA method) at the Magqu soil moisture monitoring network located in the northeastern Tibetan grasslands. The modeling results showed that by integrating the contextual information from the relatively fine spatial resolution MODIS products, spatial soil moisture representations were significantly improved. The PKU method produced the most accurate spatially disaggregated soil moisture among the four methods. In conclusion, the PKU method developed in this study is a practical and efficient approach for improving spatial representations of the coarse spatial resolution soil moisture data derived from microwave remote sensors. Within the PKU method, our refined method for estimating the parameters of the dry-edge outperforms the traditional method.

  2. Clean development mechanism: Perspectives from developing countries

    SciTech Connect

    Sari, Agus P.; Meyers, Stephen

    1999-06-01

    This paper addresses the political acceptability and workability of CDM by and in developing countries. At COP-3 in Kyoto in 1997, the general position among developing countries changed from strong rejection of joint implementation to acceptance of CDM. The outgrowth of CDM from a proposal from Brazil to establish a Clean Development Fund gave developing countries a sense of ownership of the idea. More importantly, establishing support for sustainable development as a main goal for CDM overcame the resistance of many developing countries to accept a carbon trading mechanism. The official acceptance of CDM is not a guarantee of continued acceptance, however. Many developing countries expect CDM to facilitate a substantial transfer of technology and other resources to support economic growth. There is concern that Annex I countries may shift official development assistance into CDM in order to gain carbon credits, and that development priorities could suffer as a result. Some fear that private investments could be skewed toward projects that yield carbon credits. Developing country governments are wary regarding the strong role of the private sector envisioned for CDM. Increasing the awareness and capacity of the private sector in developing countries to initiate and implement CDM projects needs to be a high priority. While private sector partnerships will be the main vehicle for resource transfer in CDM, developing country governments want to play a strong role in overseeing and guiding the process so that it best serves their development goals. Most countries feel that establishment of criteria for sustainable development should be left to individual countries. A key issue is how CDM can best support the strengthening of local capacity to sustain and replicate projects that serve both climate change mitigation and sustainable development objectives.There is support among developing countries for commencing CDM as soon as possible. Since official commencement must

  3. Cooperation and Development

    ERIC Educational Resources Information Center

    M'Bow, Amadou-Mahtar

    1976-01-01

    International economic relations are discussed in terms of cultural, educational, and communications development globally. It is emphasized that global cooperation and development are necessary for development of people and societies. (ND)

  4. SIRU development. Volume 1: System development

    NASA Technical Reports Server (NTRS)

    Gilmore, J. P.; Cooper, R. J.

    1973-01-01

    A complete description of the development and initial evaluation of the Strapdown Inertial Reference Unit (SIRU) system is reported. System development documents the system mechanization with the analytic formulation for fault detection and isolation processing structure; the hardware redundancy design and the individual modularity features; the computational structure and facilities; and the initial subsystem evaluation results.

  5. Developing Teachers: Improving Professional Development for Teachers

    ERIC Educational Resources Information Center

    Coe, Robert; Aloisi, Cesare; Higgins, Steve; Major, Lee Elliot

    2015-01-01

    This document is a summary of the report "What Makes Great Teaching". It argues that improved teacher ­development will positively impact on pupil attainment, particular those from disadvantaged backgrounds. "Developing Teachers" presents five policy recommendations which have been signed by 17 of Britain's leading headteachers…

  6. Curriculum Development: Teacher Involvement in Curriculum Development

    ERIC Educational Resources Information Center

    Alsubaie, Merfat Ayesh

    2016-01-01

    In order for curriculum development to be effective and schools to be successful, teachers must be involved in the development process. An effective curriculum should reflect the philosophy, goals, objectives, learning experiences, instructional resources, and assessments that comprise a specific educational program ("Guide to curriculum…

  7. Child Development Associate. Body Skills Development.

    ERIC Educational Resources Information Center

    Office of Child Development (DHEW), Washington, DC.

    This Child Development Associate (CDA) training module, one of a series of 18, is intended to provide the intern with the knowledge and skills necessary for helping children develop their body skills. The module stipulates competency-based objectives and provides essential information, suggestions, examples and learning activities on three topics…

  8. Developing New Models for Collection Development.

    ERIC Educational Resources Information Center

    Stoffle, Carla J.; Fore, Janet; Allen, Barbara

    1999-01-01

    Discusses the need to develop new models for collection development in academic libraries, based on experiences at the University of Arizona. Highlights include changes in the organizational chart; focusing on users' information goals and needs; integrative services; shared resources; interlibrary loans; digital technology; and funding. (LRW)

  9. Ceramic brush seals development

    NASA Technical Reports Server (NTRS)

    Howe, Harold

    1994-01-01

    The following topics are discussed in this viewgraph presentation: ceramic brush seals, research and development, manufacturing, brazed assembly development, controlling braze flow, fiber selection, and braze results.

  10. Quantitative fluorescence detection of phenylalanine in blood spots on filter paper

    NASA Astrophysics Data System (ADS)

    Li, Yuezhi; Liu, Fengjun; Wang, Xuemin; Xu, Gang

    2007-11-01

    Phenylketonuria is a genetic disease, which causes the metabolization disorder of phenylalanine, this disorder would damage the neural system of infants as a result of the accumulation of phenylalanine in blood. Therefore, it is of great importance to diagnose and treat phenylketonuria as early as possible for newborns. The aim of this paper is to develop a fluorescence detection system to measure blood phenylalanine concentration of new-born infants. In this design, a high luminance ultraviolet LED is used for excitation source, and a kind of bifurcated optical fiber assembly is applied for conduction of light. The excitation source is filtered and coupled into quartz fibers of the bifurcated fiber assembly for conduction of light to excite the fluorescence of phenylalanine in blood sample. The collected fluorescence is transmitted along the glass fibers of the assemblies and coupled to a photomultiplier tube. The fluorescence is filtered with 470~500 nm band-pass filter to subdue scattered excitation light and to limit the spectral width of the detected fluorescence. By the comparison with a standard instrument, the new system with low power consumption, low cost and small size is also proven sensitive and accurate, which meets the demand of clinical phenylketonuria screening.

  11. Education and Development: A Developing Theme

    NASA Astrophysics Data System (ADS)

    Brock-Utne, Birgit

    2002-03-01

    The following article is based on an analysis of selected examples from the approximately 2500 main articles that have been published in the International Review of Education ( IRE) since its inception in 1931 until the fall of 2001. The scope of the topic is education within developing countries and the promotion of such education by industrialised countries and development agencies. After an introduction on the growth of the concern over education and development over seven decades of the journal, three themes are looked at in some more detail: (1) The discussion on nationalism versus internationalism in education, a theme that bears clear relevance to the field "Education and Development" and has been with the journal from its inception but on which one finds more emphasis in the earlier volumes. (2) The language of instruction in developing countries. This theme has also been with the journal from its inception and it is still much debated. (3) The effects of external aid on the education sector in developing countries. Though massive economic aid in the form of grants or loans to the education sector in developing countries is of more recent nature external influence on the education sector has been there since colonial times.

  12. Options for developing countries in mining development

    SciTech Connect

    Walrond, G.W.; Kumar, R.

    1985-01-01

    This book is a study of the issues that developing countries face in planning and implementing mineral development, taking as case studies Botswana, Sierra Leone, Zambia, Tanzania, Malaysia, Papua New Guinea and the developed states of Quebec and Western Australia. The authors consider the major aspects of the matter including organization and administration; regulation; taxation and surplus distribution; the dynamics of such instruments as royalty, rent resource tax and capital allowances under various cost/price scenarios; and selected mining agreements and their key provisions. They stress throughout the need for foreign investment while maximizing the economic benefits reaped from exhaustible resources.

  13. Geothermal development opportunities in developing countries

    SciTech Connect

    Kenkeremath, D.C.

    1989-11-16

    This report is the proceedings of the Seminar on geothermal development opportunities in developing countries, sponsored by the Geothermal Division of the US Department of Energy and presented by the National Geothermal Association. The overall objectives of the seminar are: (1) Provide sufficient information to the attendees to encourage their interest in undertaking more geothermal projects within selected developing countries, and (2) Demonstrate the technological leadership of US technology and the depth of US industry experience and capabilities to best perform on these projects.

  14. Antenna development at DARPA

    NASA Astrophysics Data System (ADS)

    Corey, Larry; Jaska, Esko

    2004-09-01

    This paper reviews recent and ongoing antenna technology and systems development in the Special Projects Office of the Defense Advanced Research Projects Agency (DARPA/SPO). These programs fall into two categories: development and application of antenna component technologies and development of transportable phased-array radar antennas. These development programs are presented in a chronological order.

  15. Energy Sources and Development.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with energy sources and development. Its objective is for the student to be able to discuss energy sources and development related to the historical perspective, biological development, current aspects, and future expectations…

  16. Leadership Development. Symposium 12.

    ERIC Educational Resources Information Center

    2000

    Three presentations are provided from the Academy of Human Resource Development (HRD) 2000 Conference Proceedings. "Leadership Development: A Review of the Theory and Literature" (Susan A. Lynham) has four parts that analyze the leadership development process: the present state of the available body of knowledge on leadership development; core…

  17. LGBT Career Development

    ERIC Educational Resources Information Center

    Gedro, Julie

    2007-01-01

    In this paper, I would like to open a conversation with my HRD colleagues about the issues related to Lesbian, Gay, Bisexual and Transgender (LGBT) career development. This paper provides some insights about LGBT career development, analyzing the factors that distinguish LGBT career development from heterosexual career development.

  18. Directions in Staff Development

    ERIC Educational Resources Information Center

    Brew, Angela, Ed.

    This collection of readings is intended to provide a source book on best practices in staff development in higher education within a British context. The 13 papers are grouped into three parts: part 1 presents the educational development tradition which has focused on development of staff as teachers; part 2 considers development of staff in…

  19. Agile Software Development

    ERIC Educational Resources Information Center

    Biju, Soly Mathew

    2008-01-01

    Many software development firms are now adopting the agile software development method. This method involves the customer at every level of software development, thus reducing the impact of change in the requirement at a later stage. In this article, the principles of the agile method for software development are explored and there is a focus on…

  20. Rural Development Issues.

    ERIC Educational Resources Information Center

    Economic Research Service (USDA), Washington, DC. Economic Development Div.

    Elements essential to an adequate framework for rural development in the U.S. are a national growth and development policy which includes a rural development strategy and definition of common problems and programmatic actions required to deal with them. Many past federal rural development programs (lacking a federal rural policy focus) have failed…

  1. Developing behavioral objectives for perioperative staff development.

    PubMed

    Beitz, J M

    1996-07-01

    Behavioral objectives (i.e., clear statements that describe intended instructional outcomes) are a crucial component of educational planning for perioperative staff development. Properly written objectives promote positive learning outcomes such as increased motivation, better retention of information, and improved instructional accountability. This article describes the advantages of using behavioral objectives, gives a historical perspective of their development, presents a practical "how-to" approach to formulating them, and delineates their link to the selection of appropriate evaluation methods. PMID:8827333

  2. Chemical probe development versus drug development.

    PubMed

    Jackson, Michael R

    2013-01-01

    Phosphatases as a class of proteins have recently attracted significant attention from the pharmaceutical industry. As our knowledge of this diverse family of proteins has grown, the relationship between phosphatases and human disease has clearly been established, with model systems proving much validation for the potential of some members of this family to be candidate drug targets. This, coupled with the fact that there have been a flood of successful drug development efforts over the past 10 years targeting protein kinases, has led some to propose that phosphatases as a class of enzymes might be equally as rich a source of drug targets as kinases. However to date there remain relatively few molecules targeting protein phosphatases in clinical development. This is less a reflection of their importance in key processes associated with disease, but rather seems to reflect inherent issues with developing drugs for many members of this family. This seems especially so for intracellular phosphatases where the development of selective, potent cell penetrant molecules with good drug-like properties has proven a formidable challenge. This chapter provides a brief outline of the two major processes that have resulted in the existing armament of chemical modulators of protein phosphatases, namely, chemical probe development and drug development. These two processes initially seem to be rather similar and while they do overlap, the stated goals of the two approaches at project initiation are distinct. PMID:23860644

  3. Hanford Site Development Plan

    SciTech Connect

    Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J. ); Yancey, E.F. )

    1990-01-01

    The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs.

  4. Hanford Site Development Plan

    SciTech Connect

    Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

    1993-05-01

    The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP`s primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans.

  5. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-07-28

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  6. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2005-01-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  7. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2005-04-30

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  8. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  9. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2003-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  10. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-04-30

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  11. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2002-07-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  12. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2002-11-01

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  13. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2001-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  14. The Developing Brain.

    ERIC Educational Resources Information Center

    Schatz, Carla J.

    1992-01-01

    Discusses neural activity and stimulation crucial in fetal brain development and the formation of the mind. Focuses on activity-dependent remodeling related to development of the visual system and retinal activity. (MCO)

  15. Developing the plan

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The basic sequence in the planning development process is discussed. Alternative ways of satisfying estimated needs, and the selection of an alternative are described along with the development of a plan to implement the selected alternative.

  16. Normal growth and development

    MedlinePlus

    ... DIET Poor nutrition can cause problems with a child's intellectual development. A child with a poor diet may be ... care provider if you have concerns about your child's growth and development. Related topics include: Developmental milestones record - 4 months ...

  17. Robotic Lander Development Project

    NASA Video Gallery

    The Robotic Lander Development Project at the Marshall Center is testing a prototype lander that will aid in the design and development of a new generation of small, smart, versatile robotic lander...

  18. Coalbed gas development

    SciTech Connect

    Not Available

    1992-01-01

    This book includes: Overview of coalbed gas development; Coalbed gas development in the West Coalbed gas development on Indian lands; Multi-mineral development conflicts; Statutory solutions to ownership disputes; State and local regulation; Environmental regulations; Status of the section 29 tax credit extension; Using the section 29 credit; Leasing coalbed gas prospects; Coalbed gas joint operating agreements and Purchase and sale agreements for coalbed gas properties.

  19. Gammasphere software development

    SciTech Connect

    Piercey, R.B.

    1993-01-01

    Activities of the nuclear physics group are described. Progress was made in organizing the Gammasphere Software Working Group, establishing a nuclear computing facility, participating in software development at Lawrence Berkeley, developing a common data file format, and adapting the ORNL UPAK software to run at Gammasphere. A universal histogram object was developed that defines a file format and provides for an objective-oriented programming model. An automated liquid nitrogen fill system was developed for Gammasphere (110 Ge detectors comprise the sphere).

  20. Dental Curriculum Development in Developing Countries.

    ERIC Educational Resources Information Center

    Phantumvanit, Prathip

    1996-01-01

    Since establishment of formal dental education in Southeast Asia, changes stemming from research and technology have led to dental curriculum changes. Development of the dental curriculum can be divided into three phases: disease oriented; health oriented; and community oriented. Evolution of these phases is traced in the dental curricula of Laos,…

  1. Essays on Child Development in Developing Countries

    ERIC Educational Resources Information Center

    Humpage, Sarah Davidson

    2013-01-01

    This dissertation presents the results of three field experiments implemented to evaluate the effectiveness of strategies to improve the health or education of children in developing countries. In Guatemala, community health workers at randomly selected clinics were given patient tracking lists to improve their ability to remind parents when their…

  2. Cultural Energy & Grassroots Development.

    ERIC Educational Resources Information Center

    Kleymeyer, Charles D.

    1992-01-01

    Discusses how cultural vitality drives successful community development. Links cultural, community, and environmental values. Examines successes and failures of programs attempting to link culture and development in Panama, Ecuador, and Colombia. Examines role of cultural self-examination for creating new development paradigm. Examines prospects…

  3. Teachers as Course Developers.

    ERIC Educational Resources Information Center

    Graves, Kathleen, Ed.

    The collection of essays on teachers as course developers is designed to help teachers understand how to develop courses or modify existing ones using their own experience and the experiences and theories of others. It attempts to capture this process through the stories of six teachers who have developed courses. Each narrative focuses on a…

  4. Science and Development

    ERIC Educational Resources Information Center

    Auger, Pierre

    1973-01-01

    The relation between science and socioeconomic development in both developed and developing countries is discussed. The interdependence of pure and applied science, technology and finance, knowledge and tradition, and national, regional, and world-wide efforts in behalf of progress are characterized. (BL)

  5. Developing Large CAI Packages.

    ERIC Educational Resources Information Center

    Reed, Mary Jac M.; Smith, Lynn H.

    1983-01-01

    When developing large computer-assisted instructional (CAI) courseware packages, it is suggested that there be more attentive planning to the overall package design before actual lesson development is begun. This process has been simplified by modifying the systems approach used to develop single CAI lessons, followed by planning for the…

  6. Marketing Human Resource Development.

    ERIC Educational Resources Information Center

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  7. PHOTOGRAPHIC FILM DEVELOPER

    DOEpatents

    Berry, F.G.

    1958-06-24

    S>An improved photographic developer is presented having very high energy development fine grain characteristics and a long shelf life. These characteristics are obtained by the use of aminoacetic acid in the developer, the other constituents of which are: sodium sulfite, hydroquinone, sodiunn borate, boric acid and potassium bromide, 1-phenyl-3-pyrazolidone.

  8. Moral Development in Adolescence

    ERIC Educational Resources Information Center

    Hart, Daniel; Carlo, Gustavo

    2005-01-01

    Themes in the papers in this special issue of the "JRA" on moral development are identified. We discuss the intersection of moral development research with policy concerns, the distinctive qualities of moral life in adolescence that warrant investigation, the multiple connotations of "moral", the methods typical of moral development research, and…

  9. Bilingualism and Cognitive Development.

    ERIC Educational Resources Information Center

    Caraballo, Jose N.

    Research on the effects of bilingualism on cognitive development is reviewed, and two complementary models of bilingualism are developed to account for research results. It is suggested that research since 1960 shows a positive relationship between bilingualism and cognitive development, at least for some types of bilingualism. The advantage or…

  10. Developing Workplace Education Curriculum.

    ERIC Educational Resources Information Center

    Burkhart, Jennifer

    This guide, which is intended for project directors, coordinators, and other professional staff involved in developing/delivering workplace education programs, explains the process of developing a functional context workplace education curriculum. Discussed first are the following: the types of information needed to develop a functional context…

  11. CRITICAL READING DEVELOPS EARLY.

    ERIC Educational Resources Information Center

    LEE, DORRIS; AND OTHERS

    THIS ISSUE OF THE READING AIDS SERIES PRESENTS A DISCUSSION OF THE POTENTIAL FOR CRITICAL READING AMONG YOUNG CHILDREN AND HOW IT CAN BE DEVELOPED. IT OFFERS SUGGESTIONS FOR THE MAXIMUM DEVELOPMENT OF THINKING SKILLS AND ATTITUDES OF INQUIRY AND EVALUATION. SOME OF THE TOPICS DISCUSSED ARE -- (1) THE DEVELOPMENT OF PERCEPTS, CONCEPTS, AND COMMON…

  12. Development Communication Report, 1993.

    ERIC Educational Resources Information Center

    Bosch, Andrea, Ed.

    1993-01-01

    The three 1993 issues of the newsletter "Development Communication Report" focus on the use of communication technologies in developing countries to educate the people about various social issues as well as the field of development communication itself. Agricultural communication is the theme of the first issue which contains the following…

  13. Software development in Ada

    NASA Technical Reports Server (NTRS)

    Basili, V. R.; Katz, E. E.

    1985-01-01

    Ada will soon become a part of systems developed for the US Department of Defense. NASA must determine whether it will become part of its environment and particularly whether it will become a part fo the space station development. However, there are several issues about Ada which should be considered before this decision is made. One means of considering these issues is the examination of other developments in Ada. Unfortunately, few full scale developments have been completed or made publicly available for observation. Therefore, it will probably be necessary to study an Ada development in a NASA environment. Another means related to the first is the development of Ada metrics which can be used to characterize and evaluate Ada developments. These metrics need not be confined to full scale developments and could be used to evaluate on going projects as well. An early development in Ada, some observations from that development, metrics which were developed for use with Ada, and future directions for research into the use of Ada in software development in general and in the NASA Goddard environment in particular are described.

  14. Molecular biology of development

    SciTech Connect

    Davidson, E.H.; Firtel, R.A.

    1984-01-01

    This book is a compilation of papers presented at a symposium on the molecular biology of development. Topics discussed include: cytoplasmic localizations and pattern formations, gene expression during oogenesis and early development, developmental expression of gene families molecular aspects of plant development and transformation in whole organisms and cells.

  15. World Development Report 1984.

    ERIC Educational Resources Information Center

    World Bank, Washington, DC.

    This report, seventh in a series of annual publications, examines the relationship between population change and development, showing why continuing rapid population growth in developing countries is likely to mean a lower quality of life for millions of people. The first part of the report concludes that the economies of developing countries can…

  16. Curriculum Development in Geomorphology.

    ERIC Educational Resources Information Center

    Gregory, Kenneth J.

    1988-01-01

    Examines the context of present curriculum development in geomorphology and the way in which it has developed in recent years. Discusses the content of the geomorphology curriculum in higher education and the consequences of curriculum development together with a consideration of future trends and their implications. (GEA)

  17. Language and Psychological Development.

    ERIC Educational Resources Information Center

    Gleason, Jean Berko

    Input language may have an effect on child development that goes far beyond language development alone. Language is the medium by which children acquire at least a portion of their sex role and social class or group characteristics, world view, and emotional and psychological well-being. Existing theories of psychological development ignore…

  18. Prodder's Development Annual, 1988.

    ERIC Educational Resources Information Center

    van der Kooy, R. J. W., Ed.

    This collection of reports examines the current state of development in southern Africa, in general, and in South Africa, in particular. The introduction, "A Development Perspective of Southern Africa" (R. J. W. van der Kooy), briefly reviews the history of southern African development, and discusses purposes, approaches, and progress. Sixteen…

  19. Mechanisms in Plant Development

    SciTech Connect

    Hake, Sarah

    2013-08-21

    This meeting has been held every other year for the past twenty-two years and is the only regularly held meeting focused specifically on plant development. Topics covered included: patterning in developing tissues; short and long distance signaling; differentiation of cell types; the role of epigenetics in development; evolution; growth.

  20. Redefining Professional Development. Newsletter

    ERIC Educational Resources Information Center

    Center for Comprehensive School Reform and Improvement, 2006

    2006-01-01

    The research on effective professional development is consistent across many studies. Researchers Willis Hawley and Linda Valli (Westchester Institute for Human Services Research, n.d.), in their synthesis of the professional development literature, find that high-quality teacher development is as follows: (1) Informed by research on teaching and…

  1. Beyond Curriculum Development.

    ERIC Educational Resources Information Center

    Schutz, Richard R.

    The methodology of research and the technology of development in education have advanced beyond "curriculum development," as activities associated with that rubric are popularly practiced. These advances provide the experiential basis for five actionable conclusions: (1) Programmatic development of integrated resources for use by students,…

  2. Metabolite amyloids: a new paradigm for inborn error of metabolism disorders.

    PubMed

    Gazit, Ehud

    2016-07-01

    The formation of ordered amyloid assemblies is associated with major human degenerative disorders, including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. Amyloid fibrils are elongated nanoscale structures that bind to specific dyes (including thioflavin T and Congo red). Amyloid fibrillar assemblies or their early intermediates are known to induce apoptotic cytotoxic effect. Until recently, amyloid fiber formation was observed only with proteins and peptides. We reported in 2012 that a single amino acid, phenylalanine, could also form typical amyloid fibrils with the same morphology, dye-binding specificity, and electron diffraction pattern as protein amyloids. X-ray crystallography demonstrated the formation of supramolecular β-sheet-like organization by phenylalanine at its zwitterionic form. Metabolite amyloids had pronounced cytotoxicity that could be depleted by treatment with antibodies raised against the phenylalanine structures. We suggested that the observed amyloid formation could explain some of the symptoms observed in phenylketonuria (PKU) upon the accumulation of phenylalanine. Follow-up studies by other groups revealed the ability of phenylalanine amyloids to bind to membranes, as observed with protein amyloids. Furthermore, the doxycycline amyloid formation inhibitor was shown to also affect the formation of phenylalanine amyloids. In 2015, it was reported that other metabolites involved in metabolic disorders, including adenine, uracil, tyrosine, and orotic acid, could form amyloid-like assemblies. It was further demonstrated that the assemblies induce apoptotic cell death. Taken together, we suggest a new hypothesis to understand the etiology of degenerative processes observed in inborn error of metabolism disorders and indicate new avenues for treatment. PMID:27271695

  3. CpG methylation accounts for a recurrent mutation (c.1222C>T) in the human PAH gene.

    PubMed

    Murphy, B C; Scriver, C R; Singh, S M

    2006-09-01

    The human PAH gene (GenBank: U49897.1 (cDNA), AF404777 (gDNA)) harbors alleles that either cause or are associated with hyperphenylalaninemia and phenylketonuria (http://www.pahdb.mcgill.ca). Mutation analysis has identified approximately 500 alleles of which approximately 30 produce polymorphic core haplotypes. The c.1222C>T allele (p.R408W) is the most prevalent and widely encountered PKU-causing allele. Because it occurs on multiple locus-specific polymorphic haplotypes, it is probably not identical by descent in different populations. This mutation involves a CpG dinucleotide in a so-called "hypermutable" codon suggesting that c.1222C>T could be a recurrent allele following spontaneous methylation-mediated deamination of 5 mC. This concept is widely assumed and accepted but the 5mC status of hypermutable codons has seldom been confirmed. We show that the PAH c.1222C nucleotide is indeed methylated (c.1222 mC) in somatic genomes (leukocyte and brain) of H. sapiens. Examination of a representative region in exon 12 (and also in exon 7) in the PAH gene shows that 5 mC is restricted to cytosines in CpG dinucleotides in the hypermutable codons. The methylation pattern seen in human PAH exon 12 was also observed in the corresponding codon in three nonhuman primates. The finding offers at least one explanation for the high relative frequency of the c.1222C>T (p.R408W) allele in the human population. PMID:16917891

  4. Site Development Planning Handbook

    SciTech Connect

    1981-01-01

    The Handbook provides facility managers and site planners at DOE organizations responsible for planning site developments and facilities utilization a step-by-step planning checklist to ensure that planners at each site are focusing on Department-wide goals and objectives. It begins with a brief discussion of a site development-by-objectives program design to promote, recognize, and implement opportunities for improvements in site utilization through planning. Additional information is included on: assembling existing data, plans, programs, and procedures; establishing realistic objectives; identifying site problems, opportunities; and development needs; determining priorities among development needs; developing short and long-range plans; choosing the right development solutions and meeting minimum legal site restrictions; presenting the plan; implementing elements of the plan; monitoring and reporting plan status; and modifying development program plans. (MCW)

  5. Geothermal energy development

    SciTech Connect

    Butler, E.W.; Pick, J.B.

    1983-01-01

    This book studies the impact of geothermal energy development in Imperial County, California. An integrated assessment model for public policy is presented. Geothermal energy resources in Imperial County are identified. Population and employment studies project the impact of geothermal on demography and population movement in the county. A public opinion, and a leadership opinion survey indicate support for well-regulated geothermal development. Actual development events are updated. Finally, research conclusions and policy recommendations are presented.

  6. Fusion development and technology

    SciTech Connect

    Montgomery, D.B.

    1992-01-01

    This report discusses the following: superconducting magnet technology; high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies--aries; ITER physics: alpha physics and alcator R D for ITER; lower hybrid current drive and heating in the ITER device; ITER superconducting PF scenario and magnet analysis; ITER systems studies; and safety, environmental and economic factors in fusion development.

  7. Composite Tank Development

    NASA Technical Reports Server (NTRS)

    DeLay, Thomas K.

    2000-01-01

    This paper presents viewgraphs on composite tank development. There is a need for oxidizer tanks and reliable, lightweight fuel. The need for cost-effective and scalable manufacturing is also evident. In order to achieve these goals, tooling methods for tank development must be applied, methods for producing easily adaptable and scalable vessel liners must be developed, insulation layer or protective barriers for containers must be manufactured, and an appropriate fiber/resin system for composite overwrap structures must be identified.

  8. Climate and development

    SciTech Connect

    Biswas, A.K.

    1984-01-01

    The authors review the existing knowledge on the inter-relationships between climate and patterns of development; the impact variables on water and agricultural development; and the effects of climate on human health. A case study is also given of the effect of climatic fluctuations on human population in Mesopotamia. Contents: Climate and Development; Climate and Agriculture; Climate and Water Management; Climate and Health; Effects of Climate Fluctation on Human Populations; Study of Mesopotamian Society.

  9. Renewable energy project development

    SciTech Connect

    Ohi, J.

    1996-12-31

    The author presents this paper with three main thrusts. The first is to discuss the implementation of renewable energy options in China, the second is to identify the key project development steps necessary to implement such programs, and finally is to develop recommendations in the form of key issues which must be addressed in developing such a program, and key technical assistance needs which must be addressed to make such a program practical.

  10. Blind shaft development

    SciTech Connect

    Fiscor, S.

    2009-02-15

    The article discusses how Shaft Drillers International (SDI) is breaking new ground in shaft development and ground stabilization. Techniques of blind shaft drilling and raise bore shaft development developed by SDI are briefly explained. An associated company, Coastal Drilling East, deals with all types of ground improvement such as pre-grouting work for shafts, grouting of poor soil and water leaks into the mine. 3 photos.

  11. Intelligence as Developing Expertise.

    PubMed

    Sternberg

    1999-10-01

    This essay describes how intelligence can be viewed as developing expertise. The general conception of intelligence as developing expertise is described. Then research examples are given that, in conjunction, seem odd under traditional interpretations of abilities but that make sense as a whole in the context of the developing-expertise model. It is concluded that this new model offers potential for better understanding intelligence-related phenomena. Copyright 1999 Academic Press. PMID:10508532

  12. Avionics advanced development strategy

    NASA Technical Reports Server (NTRS)

    Dyer, D.

    1990-01-01

    Discussed here is the problem of how to put together an integrated, phased, and affordable avionics advanced development program that links and applies to operational, evolving, and developing programs/vehicles, as well as those in the planning phases. Collecting technology needs from individual programs/vehicles and proposed technology items from individual developers usually results in a mismatch and something that is unaffordable. A strategy to address this problem is outlined with task definitions which will lead to avionics advanced development items that will fit within an overall framework, prioritized to support budgeting, and support the scope of NASA space transportations needs.

  13. [Apoptosis during embryo development].

    PubMed

    Jezek, Davor; Kozina, Viviana

    2009-10-01

    The development of human embryo includes two essential processes, i.e., rapid mitotic activity of cells and gradual differentiation of tissues and organs. The latter process is very often characterized by extensive migration of cells from their site of origin to the site of definitive location, inductive action of the neighboring germ layers and programmed cell death (apoptosis). This paper describes examples of proliferative and apoptotic processes during the development of human embryo. The development of trilaminar germ disk, skin, gonads, central and peripheral nerve system as well as limbs provides instructive examples of how apoptosis regulates the development and differentiation of cells. PMID:19999545

  14. Exploration Technology Development & Demonstration

    NASA Video Gallery

    Chris Moore delivers a presentation from the Exploration Technology Development & Demonstration (ETDD) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX....

  15. Halbach Magnetic Rotor Development

    NASA Technical Reports Server (NTRS)

    Gallo, Christopher A.

    2008-01-01

    The NASA John H. Glenn Research Center has a wealth of experience in Halbach array technology through the Fundamental Aeronautics Program. The goals of the program include improving aircraft efficiency, reliability, and safety. The concept of a Halbach magnetically levitated electric aircraft motor will help reduce harmful emissions, reduce the Nation s dependence on fossil fuels, increase efficiency and reliability, reduce maintenance and decrease operating noise levels. Experimental hardware systems were developed in the GRC Engineering Development Division to validate the basic principles described herein and the theoretical work that was performed. A number of Halbach Magnetic rotors have been developed and tested under this program. A separate test hardware setup was developed to characterize each of the rotors. A second hardware setup was developed to test the levitation characteristics of the rotors. Each system focused around a unique Halbach array rotor. Each rotor required original design and fabrication techniques. A 4 in. diameter rotor was developed to test the radial levitation effects for use as a magnetic bearing. To show scalability from the 4 in. rotor, a 1 in. rotor was developed to also test radial levitation effects. The next rotor to be developed was 20 in. in diameter again to show scalability from the 4 in. rotor. An axial rotor was developed to determine the force that could be generated to position the rotor axially while it is rotating. With both radial and axial magnetic bearings, the rotor would be completely suspended magnetically. The purpose of this report is to document the development of a series of Halbach magnetic rotors to be used in testing. The design, fabrication and assembly of the rotors will be discussed as well as the hardware developed to test the rotors.

  16. Population, environment and development.

    PubMed

    Karkal, M

    1994-06-01

    Western development models label subsistence economies, which do not participate in the market economy on a grand scale and do not consume commodities produced for and distributed through the market, to be poor. Yet, subsistence does not always indicate a low quality of life. The Western development process has destroyed wholesome and sustainable lifestyles. In India, the Green Revolution caused many small farmers to lose their land. In comparison to traditional economies, industrial economies have longer technological chains dependent on higher energy and resource inputs and exclude large numbers of people without power to buy goods. Further, they generate new and artificial needs, necessitating increased production of industrial goods and services. They erode resource bases for survival. This erosion is marginalizing people who were traditionally in nature's economy. Developed countries did not deliver 0.15% of their GNP to development projects in developing countries as promised. The US made population growth in these countries its cause. The UN and other multinational agencies during 1962-1972, at the US's request, began to support population and family planning programs in developing countries. These countries opposed the 1st draft at the 1974 Bucharest Population Conference, but by the conference in Mexico City, most supported the need for family planning. Yet, the US politicized this conference and had a greater say in the recommendations than did developing countries. Structural adjustments and external debt repayments required of developing countries in the 1980s set them back. In fact, the number of developing countries increased from 31 to 42. The UN recognizes the right to development, but social inequalities are barriers to this right. If environmental degradation continues, poverty will only increase. Women's groups are playing a great role in preparations for the International Conference on Population and Development in Cairo in September 1994. PMID

  17. Guidelines for Program Development.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg. Literacy and Continuing Education Branch.

    This guide, which is intended to assist developers of community-based adult literacy programs in Manitoba, explains the following components of good programming and presents suggestions for integrating them into literacy provision: community outreach, program development, learner involvement, provision of appropriate staffing, use of volunteers,…

  18. Spiritual Growth and Development.

    ERIC Educational Resources Information Center

    Wakefield, Dara V.

    Spiritual living demands growth, and spiritual development has many parallels with human development. Ministers who are knowledgeable of the various stages are best prepared to assist and optimize spiritual growth. The primary benefit of nurturing believers through developmental stages is assured spiritual health and maturity in the context of a…

  19. Development Communication Report, 1992.

    ERIC Educational Resources Information Center

    Development Communication Report, 1992

    1992-01-01

    The four issues of the quarterly newsletter contained in this document focus on the use of communication technologies in developing countries to educate the people about various social issues as well as the field of development communication itself. Environment and communication is the theme of the first issue, which includes articles on…

  20. Development. Courier No. 26.

    ERIC Educational Resources Information Center

    ASPBAE Courier Service, 1982

    1982-01-01

    This journal contains a series of articles dealing with the theme of development in Asia and rural Indonesia. Included in the journal are the following articles: "Nonformal Education in Rural Areas of Developing Countries," by members of the Rural Project Team from the Centre for Continuing Education at Australian National University; "Application…

  1. Development of IVF Children.

    ERIC Educational Resources Information Center

    van Balen, Frank

    1998-01-01

    Examines physical and psychological development of children conceived through in vitro fertilization (IVF), focusing on questions related to risk of congenital defects or mental retardation and impact on the parent-child relationship. Concludes that no serious problems have arisen concerning the physical and psychological development of IVF…

  2. [Population Growth and Development].

    ERIC Educational Resources Information Center

    Clausen, A. W.

    Rapid population growth as a central development problem, the proper domain of government in reducing population growth, and effective measures which can be taken to reduce fertility are examined. Rapid population growth puts a brake on development because it exacerbates the difficult choice between higher consumption now and the investment needed…

  3. Handbook of Moral Development

    ERIC Educational Resources Information Center

    Killen, Melanie; Smetana, Judith

    2006-01-01

    The psychological study of moral development has expanded greatly, both in terms of the diversity of theoretical perspectives that are represented in the field, as well as in the range of topics that have been studied. This "Handbook of Moral Development" represents the diversity and multidisciplinary influences on current theorizing about the…

  4. Jamaica: A Development Perspective.

    ERIC Educational Resources Information Center

    Scott, Rosalind; And Others

    Jamaica is known mainly as a tourist playground and the home of Reggae music. This Jamaican teaching unit dispels stereotypes and shows Jamaica for what it really is--an economically-troubled, developing nation. The unit illustrates the challenges this island nation is facing in its struggle toward economic development. Contents are: Teacher…

  5. Youth Development: Maori Styles

    ERIC Educational Resources Information Center

    Ware, Felicity; Walsh-Tapiata, Wheturangi

    2010-01-01

    Despite the innovative approach of the Youth Development Strategy Aotearoa and the applicability of its Rangatahi Development Package, the diverse realities and experiences of Maori youth are still presenting unique challenges to national policy in Aotearoa New Zealand. A Maori youth research approach that utilised a combination of action research…

  6. Developing Young Investigators

    ERIC Educational Resources Information Center

    Shaw, Liz; Woodbridge, Jenny; Pearson, Sue

    2003-01-01

    The Early Excellence centre was established in 1999 to undertake early years curriculum development in the North West, Yorkshire and Humberside regions. As part of development work, small research projects are commissioned in early years settings. This article describes how the authors worked with Wingate Community Nursery School. The work was…

  7. Technical Assistance to Developers

    SciTech Connect

    Rockward, Tommy; Borup, Rodney L.; Garzon, Fernando H.; Mukundan, Rangachary; Spernjak, Dusan

    2012-07-17

    This task supports the allowance of technical assistance to fuel-cell component and system developers as directed by the DOE. This task includes testing of novel materials and participation in the further development and validation of single cell test protocols. This task also covers technical assistance to DOE Working Groups, the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Driving Research and Innovation for Vehicle efficiency and Energy sustainability (U.S. Drive) Fuel Cell Technology Team. Assistance includes technical validation of new fuel cell materials and methods, single cell fuel cell testing to support the development of targets and test protocols, and regular advisory participation in other working groups and reviews. This assistance is made available to PEM fuel cell developers by request and DOE Approval. The objectives are to: (1) Support technically, as directed by DOE, fuel cell component and system developers; (2) Assess fuel cell materials and components and give feedback to developers; (3) Assist the DOE Durability Working Group with the development of various new material durability Testing protocols; and (4) Provide support to the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Fuel Cell Technology Team. FY2012 specific technical objectives are: (1) Evaluate novel MPL materials; (2) Develop of startup/ shutdown protocol; (3) Test the impact of hydrophobic treatment on graphite bi-polar plates; (4) Perform complete diagnostics on metal bi-polar plates for corrosion; and (5) Participate and lead efforts in the DOE Working Groups.

  8. Developing Environmental Study Areas.

    ERIC Educational Resources Information Center

    Wert, Jonathan M.

    This publication is designed to help the teacher in developing environmental study areas. Numerous examples of study areas, including airports, lakes, shopping centers, and zoos, are listed. A current definition of environmental study areas is given and guidelines for their development and identification are included. The appendix, which comprises…

  9. Developing Successful Global Leaders

    ERIC Educational Resources Information Center

    Training, 2011

    2011-01-01

    Everyone seems to agree the world desperately needs strong leaders who can manage a global workforce and all the inherent challenges that go with it. That's a big part of the raison d'etre for global leadership development programs. But are today's organizations fully utilizing these programs to develop global leaders, and, if so, are they…

  10. VOCABULARY AND CONCEPT DEVELOPMENT.

    ERIC Educational Resources Information Center

    LANGER, JOHN H.

    THE PROCESSES OF THOUGHT, OF CONCEPT DEVELOPMENT, AND OF VOCABULARY DEVELOPMENT ARE SIGNIFICANTLY INTERRELATED. COMMUNICATION OF IDEAS DEPENDS UPON THE ABILITY TO ASSOCIATE WRITTEN AND VERBAL SYMBOLS WITH THE REFERENTS THROUGH A SYSTEMATIC PROCESS OF REORGANIZING AND INTEGRATING OLD AND NEW CONCEPTS. THE ABILITY TO ASSOCIATE, IN TURN, DEPENDS UPON…

  11. Strengthening Evaluation for Development

    ERIC Educational Resources Information Center

    Ofir, Zenda

    2013-01-01

    Although some argue that distinctions between "evaluation" and "development evaluation" are increasingly superfluous, it is important to recognize that some distinctions still matter. The severe vulnerabilities and power asymmetries inherent in most developing country systems and societies make the task of evaluation…

  12. PLATO Courseware Development Procedures.

    ERIC Educational Resources Information Center

    Mahler, William A.; And Others

    This is an exploratory study of methods for the preparation of computer curriculum materials. It deals with courseware development procedures for the PLATO IV computer-based education system, and draws on interviews with over 100 persons engaged in courseware production. The report presents a five stage model of development: (1) planning, (2)…

  13. Steps in Intrauterine Development.

    ERIC Educational Resources Information Center

    Barra, H. Gensini; And Others

    1996-01-01

    Recognizing the importance of health care during the perinatal period, the topic for this issue of "Children in the Tropics" is prenatal development; this issue is intended for health educators for use in educating their clients about prenatal development, health care during pregnancy, labor and delivery, and the needs of the mother and neonate…

  14. Instructional System Development.

    ERIC Educational Resources Information Center

    Department of the Air Force, Washington, DC.

    The manual presents a technology of instructional design and a model for developing and conducting efficient and cost effective Air Force instructional systems. Chapter 1 provides an overview of Instructional System Development (ISD). Chapters 2-6 each focus on a step of the process: analysis of system requirements; definition of…

  15. Developing Sustainable Leadership

    ERIC Educational Resources Information Center

    Davies, Brent, Ed.

    2007-01-01

    Developing and sustaining leaders is a major challenge for all those involved in education today. This book contains a collection of essays from recognized authors to provide insights, frameworks and ideas on how to sustain school leaders and develop values-based leadership. It also offers guidance on countering short-term management solutions,…

  16. Update on World Development.

    ERIC Educational Resources Information Center

    Social Education, 1996

    1996-01-01

    Summarizes a wealth of statistical information concerning the economic development and debt for a number of developing nations. Includes statistics on the gross national product growth of Cote d'lvoire, Guatemala, Malaysia, Korea, Colombia, and Nigeria, as well as, the gross domestic product growth and debt service for Latin America, Africa, and…

  17. Graphite technology development plan

    SciTech Connect

    1986-07-01

    This document presents the plan for the graphite technology development required to support the design of the 350 MW(t) Modular HTGR within the US National Gas-Cooled Reactor Program. Besides descriptions of the required technology development, cost estimates, and schedules, the plan also includes the associated design functions and design requirements.

  18. Information for Agricultural Development.

    ERIC Educational Resources Information Center

    Kaungamno, E. E.

    This paper describes the major international agricultural information services, sources, and systems; outlines the existing information situation in Tanzania as it relates to problems of agricultural development; and reviews the improvements in information provision resources required to support the process of agricultural development in Tanzania.…

  19. Directory of Development Activities.

    ERIC Educational Resources Information Center

    Control Data Corp., Minneapolis, Minn.

    Assembled in a loose leaf notebook, this collection of independent on-the-job activities is designed to facilitate employee development and intended to help improve an organization's performance appraisal system. The on-the-job development activities described derive from job descriptions, performance appraisal forms, and discussions with job…

  20. Staff Development Program Evaluation.

    ERIC Educational Resources Information Center

    Ashur, Nina E.; And Others

    An evaluation of the staff development program at College of the Canyons (California) was conducted in 1991 to provide information applicable to program improvement. Questionnaires were distributed to all faculty, classified staff, and flexible calendar program committee and staff development advisory committee members, resulting in response rates…

  1. Reference Model Development

    SciTech Connect

    Jepsen, Richard

    2011-11-02

    Presentation from the 2011 Water Peer Review in which principal investigator discusses project progress to develop a representative set of Reference Models (RM) for the MHK industry to develop baseline cost of energy (COE) and evaluate key cost component/system reduction pathways.

  2. Understanding Teacher Development.

    ERIC Educational Resources Information Center

    Hargreaves, Andy, Ed.; Fullan, Michael G., Ed.

    The 12 chapters in this book interpret teacher development in relation to self-development, teacher reflection, teacher biographies, cultures of teaching, teacher careers, teachers' work, gender identity, and classroom practice. The collection begins with an introductory chapter (Andy Hargreaves and Michael G. Fullan) and continues with 11…

  3. Child Development and Playgrounds.

    ERIC Educational Resources Information Center

    Frost, Joe L.

    Four major issues are explored in this study of child development research and its implications for children's playgrounds: (1) theories and philosophies of play; (2) the historical evolution of playgrounds; (3) research on child development, play, and playgrounds; and (4) creating playgrounds that meet children's developmental needs. Discussion…

  4. Towards "Astronomy for Development"

    NASA Astrophysics Data System (ADS)

    Govender, Kevindran

    2015-08-01

    The ambition of the IAU's decadal strategic plan is to use astronomy to stimulate development globally. The Office of Astronomy for Development was established in 2011 to implement this visionary plan. This talk will reflect on the past, present and future activities of the office, and describe the status of implementation of the plan at this halfway point in the 2010-2020 decade.

  5. Action in Development

    ERIC Educational Resources Information Center

    von Hofsten, Claes

    2007-01-01

    It is argued that cognitive development has to be understood in the functional perspective provided by actions. Actions reflect all aspects of cognitive development including the motives of the child, the problems to be solved, and the constraints and possibilities of the child's body and sensorimotor system. Actions are directed into the future…

  6. Developing Open Courses.

    ERIC Educational Resources Information Center

    Parer, Michael S., Ed.

    This collection of 13 articles contains the reflections of experienced course developers on a particular course that illustrates the process of constructing flagship distance education programs. "Educational Developers in Action--A Series of Tales from the Mud" (Michael Parer) is an introduction that discusses the technology of distance education,…

  7. Leadership and Management Development.

    ERIC Educational Resources Information Center

    1996

    This document contains four papers presented at a symposium on leadership and management development moderated by Mark Porter at the 1996 conference of the Academy of Human Resource Development (AHRD). "Expanding Formative Experiences: A Critical Dimension of Leadership Deportment" (Gary D. Geroy, Jackie L. Jankovich) advocates focusing leadership…

  8. University, Research, Development.

    ERIC Educational Resources Information Center

    Laroui, Abdallah

    1991-01-01

    Describes personal experiences with university research and development. Criticizes university research as ineffective and inwardly focused, resulting in a concept of scientific research that negates the notion of economic development. Complains that the focus of study no longer contributes to an increase in consumable wealth. Urges that…

  9. Early Developments, 2001.

    ERIC Educational Resources Information Center

    Buysee, Virginia, Ed.; Winton, Pam, Ed.

    2001-01-01

    This document consists of the single 2001 issue of a journal reporting new research in early childhood development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. The issue focuses on pre-kindergarten programs, highlighting a recent assessment of the skills of entering…

  10. The Development of Schemas.

    ERIC Educational Resources Information Center

    Taylor, Shelley E.; Winkler, John D.

    The term, "schema," used largely as a descriptive convenience rather than a theoretical guidepost in social psychology is examined through an analysis of its development, function, and structure. This paper articulates a model of schema development in adults by defining a schema as a representation of some stimulus domain and a set of rules or…

  11. South Korea's Economic Development.

    ERIC Educational Resources Information Center

    Ihm, Chon-Sun

    1988-01-01

    Examines South Korea's economic development from being one of the poorest nations in the world in the 1950s to becoming a "rising giant" in international trade. Surveys the path to growth, the reasons for success, and problems and new challenges facing the country as it seeks developed nation status. (GEA)

  12. Early Developments, 1998.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    1998-01-01

    This document consists of the two 1998 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. In the Spring 1998 issue, articles highlight the Center's diverse cross-cultural projects and global research, training and…

  13. Women and World Development.

    ERIC Educational Resources Information Center

    Tinker, Irene, Ed.; Bramsen, Michele Bo., Ed.

    The book presents background papers and an overview of the proceedings of the American Association of Science Seminar on Women in Development held in Mexico City in June 1975. The objectives of the seminar were to show how and why development programs fail to reach women and to emphasize the waste of human potential that has resulted. An…

  14. Leadership in Program Development.

    ERIC Educational Resources Information Center

    Moon, Sidney; Swift, Melanie

    1989-01-01

    Presented are a literature review, model, and case study for effective local program development for gifted and talented students. The model applies the research on educational change and institutional excellence to the task of developing excellent programs for gifted/talented youth in school districts of various types and sizes. (PB)

  15. Sandia microelectronics development

    SciTech Connect

    Weaver, H.T.

    1997-02-01

    An overview of the operations of Sandia`s Microelectronics Development Lab (MDL) is to develop radiation hardened IC, but techniques used for IC processing have been applied to a variety of related technologies such as micromechanics, smart sensors, and packaging.

  16. Rural Development Strategies.

    ERIC Educational Resources Information Center

    Sears, David W., Ed.; Reid, J. Norman, Ed.

    This book seeks to provide a basis for reexamining rural development policy by presenting comprehensive and current information on the effectiveness of various rural policy approaches. An introduction that defines development terminology and discusses changing policy needs is followed by 13 chapters that represent the best recent research…

  17. Chromosomal development of cancer

    SciTech Connect

    1993-12-31

    Chapter 30, describes the chromosomal development of cancer. It has been established through cytological research that the number of chromosomes in cancer cells often deviates greatly from the usual number in healthy cells of the host organism. This chapter includes discussions on chromosome studies in ascites tumors, stemline and tumor development, mitotic aberrations in cancer, and selection and tumor progression. 25 refs., 2 figs.

  18. Language and Development.

    ERIC Educational Resources Information Center

    Crooks, Tony, Ed.; Crewes, Geoffrey, Ed.

    A selection of papers presented at an international conference on the role of language in economic and social development includes: "Changing Paradigms: The Project Approach" (John McGovern); "Team Development of ELT Projects: A Case Study" (William M. Martin, Lynn P. Balabanis); "The Roles of Insiders and Outsiders in Evaluating English Language…

  19. Brain Structure and Development.

    ERIC Educational Resources Information Center

    Teyler, T.J.; Chiaia, N.

    1983-01-01

    Considers basic biology of brain, what is known of how it operates, and something of how it develops. Discusses properties of neurons and specialized regions of the brain in linguistic and higher order processing skills, as well as genetic and environmental influences on brain development. (CMG)

  20. Developing Our Water Resources

    ERIC Educational Resources Information Center

    Volker, Adriaan

    1977-01-01

    Only very recently developed as a refined scientific discipline, hydrology has to cope with a complexity of problems concerning the present and future management of a vital natural resource, water. This article examines available water supplies and the problems and prospects of water resource development. (Author/MA)

  1. University Career Development Programming

    ERIC Educational Resources Information Center

    Cochran, Donald J.; Rademacher, Betty Green

    1978-01-01

    Pertinent considerations involved in the delivery of career development services at the college level are reviewed. Specific examples of possible career programming alternatives are discussed and summarized in an organizational grid. A detailed case is included as a concrete example of career program development. (Author)

  2. Development Communication Report, 1991.

    ERIC Educational Resources Information Center

    Development Communication Report, 1991

    1991-01-01

    The four 1991 issues of the newsletter "Development Communication Report" are primarily concerned with the use of communication technologies in developing countries to educate the people. Evaluation is the theme of the first issue, which contains the following articles: "Evaluating Communication Programs: Means and Ends,""Making a Splash: How…

  3. Curriculum Development and Research.

    ERIC Educational Resources Information Center

    Tyler, Ralph W.

    Ralph W. Tyler's paper on "Curriculum Development and Research" contains examples of research findings which were or were not used in efforts to change or develop curriculum. The roles, use, and importance of action research, formulation of objectives, planning and organization of learning experiences, program assessment, relationship between…

  4. Environment and Alternative Development.

    ERIC Educational Resources Information Center

    Kothari, Rajni

    Stressing the global dimension to the adversary relationship between economic development and environmental conservation, this monograph examines the philosophical, historical, cultural, and ethnic underpinnings of modern science and technology. In addition, the monograph spells out policy implications of an alternative concept of development and…

  5. Germination and seedling development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cottonseed germination and seedling development are highly sensitive to the environment at planting and for several weeks after that. Major factors that affect germination and development are temperature, water availability, soil conditions such as compaction, rhizosphere gases, and seed and seedlin...

  6. Developing Higher Level Thinking

    ERIC Educational Resources Information Center

    Limbach, Barbara; Waugh, Wendy

    2010-01-01

    This paper identifies an interdisciplinary, five-step process, built upon existing theory and best practices in cognitive development, effective learning environments, and outcomes-based assessment. The "Process for the Development of Higher Level Thinking Skills" provides teachers with an easy to implement method of moving toward a more…

  7. Wind Economic Development (Postcard)

    SciTech Connect

    Not Available

    2011-08-01

    The U.S. Department of Energy's Wind Powering America initiative provides information on the economic development benefits of wind energy. This postcard is a marketing piece that stakeholders can provide to interested parties; it will guide them to the economic development benefits section on the Wind Powering America website.

  8. Developing Strategic Leaders.

    ERIC Educational Resources Information Center

    Carter, Patricia; Terwilliger, Leatha; Alfred, Richard L.; Hartleb, David; Simone, Beverly

    2002-01-01

    Highlights the importance of developing community college leaders capable of demonstrating strategic leadership and responding to the global forces that influence community college education. Discusses the Consortium for Community College Development's Strategic Leadership Forum and its principles, format, content, and early results. (RC)

  9. Data Centric Development Methodology

    ERIC Educational Resources Information Center

    Khoury, Fadi E.

    2012-01-01

    Data centric applications, an important effort of software development in large organizations, have been mostly adopting a software methodology, such as a waterfall or Rational Unified Process, as the framework for its development. These methodologies could work on structural, procedural, or object oriented based applications, but fails to capture…

  10. Guidance for Total Development.

    ERIC Educational Resources Information Center

    Van Hoose, William H.

    Elementary guidance, deriving much of its content from the developmental phenomena of middle childhood, is viewed as the maximization of human potentiality in the total range of the population. Included in the list of elementary school guidance objectives are (1) aiding academic development, (2) helping children develop health self-concepts, (3)…

  11. Astronomy for African development

    NASA Astrophysics Data System (ADS)

    Govender, Kevindran

    2011-06-01

    In recent years there have been a number of efforts across Africa to develop the field of astronomy as well as to reap benefit from astronomy for African people. This presentation will discuss the case of the SALT (Southern African Large Telescope) Collateral Benefits Programme (SCBP) which was set up to ensure societal benefit from astronomy. With African society as the target, the SCBP has embarked on various projects from school level education to public understanding of science to socio-economic development, the latter mainly being felt in the rural communities surrounding the South African Astronomical Observatory (home to SALT). A development plan for ``Astronomy in Africa'' will also be discussed. This plan has been drawn up with input from all over Africa and themed ``Astronomy for Education''. The Africa case stands as a good example for the IYA cornerstone project ``Developing Astronomy Globally'' which focuses on developing regions.

  12. Cleanroom software development

    NASA Technical Reports Server (NTRS)

    Dyer, M.; Mills, H. D.

    1981-01-01

    The 'cleanroom' software development process is a technical and organizational approach to developing software with certifiable reliability. Key ideas behind the process are well structured software specifications, randomized testing methods and the introduction of statistical controls; but the main point is to deny entry for defects during the development of software. This latter point suggests the use of the term 'cleanroom' in analogy to the defect prevention controls used in the manufacturing of high technology hardware. In the 'cleanroom', the entire software development process is embedded within a formal statistical design, in contrast to executing selected tests and appealing to the randomness of operational settings for drawing statistical inferences. Instead, random testing is introduced as a part of the statistical design itself so that when development and testing are completed, statistical inferences are made about the operation of the system.

  13. JPL antenna technology development

    NASA Technical Reports Server (NTRS)

    Freeland, R. E.

    1982-01-01

    Systems-level technology for evolving cost-effective, STS compatible antennas that will be automatically deployed in orbit to perform a variety of missions in the 1985 to 2000 time period is discussed. For large space-based antenna systems, the LSST program has selected deployable antennas for development. The maturity of this class of antenna, demonstrated by the success of smaller size apertures, provides a potential capability for satisfying a significant number of near-term, space-based applications. The offset wrap-rib concept development is the basis of the JPL LSST antenna technology development program. Supporting technology to the antenna concept development include analytical performance prediction, the capability for measuring and evaluating mechanical antenna performance in the intended service environment, and the development of candidate system-level configurations for potential applications utilizing the offset wrap-rib antenna concept.

  14. Quality Development in Education

    NASA Astrophysics Data System (ADS)

    Panetsos, Spiros; Zogopoulos, Anastasios; Tigas, Odysseas; Gubaidullina, Albina

    The article suggests that people involved in quality development need a specific competence, called quality literacy, in order to successfully improve learning processes. Quality literacy is viewed as a set of competencies that are needed for professional quality development. Quality literacy emphasizes the importance of professionalism as a necessary component for quality development, in addition to structural quality management models. Quality development is a co-production between learners and their learning environment. This means that the educational process can only be influenced and optimized through participation and not steered externally. Quality strategies cannot, therefore, guarantee a high quality of learning processes but rather aim at professionalisation of the educational process. This article suggests participation and negotiation between educational participants (clients and providers) as a main condition for quality development.

  15. Aggressive development plans

    SciTech Connect

    McCandless, D.H.

    1993-11-01

    Hydropower developments are capital-intensive, are subject to uncertainty in water availability, and have a somewhat higher construction-cost risk than thermal projects. However, a developer who selects an attractive site, arranges a good financial package, and designs and constructs a well-conceived hydropower project can earn an attractive long-term return while providing a dependable, low-cost source of energy to consumers. In the Philippines, many attractive hydropower sites are now available. As demonstrated by the attendance at the US Trade and Development Agency-sponsored Symposium on Power Development and Investment Opportunities in the Philippines, in Washington, D.C., on Sept. 21 and 22, 1993, there is a growing interest in private hydropower. Following its successful record in implementing thermal private power developments, the Philippines now offers many attractive opportunities to exploit its tremendous potential in the hydropower sector.

  16. Liga developer apparatus system

    DOEpatents

    Boehme, Dale R.; Bankert, Michelle A.; Christenson, Todd R.

    2003-01-01

    A system to fabricate precise, high aspect ratio polymeric molds by photolithograpic process is described. The molds for producing micro-scale parts from engineering materials by the LIGA process. The invention is a developer system for developing a PMMA photoresist having exposed patterns comprising features having both very small sizes, and very high aspect ratios. The developer system of the present invention comprises a developer tank, an intermediate rinse tank and a final rinse tank, each tank having a source of high frequency sonic agitation, temperature control, and continuous filtration. It has been found that by moving a patterned wafer, through a specific sequence of developer/rinse solutions, where an intermediate rinse solution completes development of those portions of the exposed resist left undeveloped after the development solution, by agitating the solutions with a source of high frequency sonic vibration, and by adjusting and closely controlling the temperatures and continuously filtering and recirculating these solutions, it is possible to maintain the kinetic dissolution of the exposed PMMA polymer as the rate limiting step.

  17. Laser forming process development

    SciTech Connect

    Blake, R.J.

    1996-12-31

    This paper is a summary of the activities performed for the process development of laser thermal forming sheet metal parts in support of rapid prototyping. A 400 watt pulsed Nd:YAG laser and 50 watt desktop CO{sub 2} laser were used during initial process development. Several tool-assisted laser forming approaches were conceived during the development of the process, and simple fixtures for process development/understanding were used throughout all testing. Much of the actual forming was performed with the base material in an unfixtured state. CRES (304) was used for baseline development, but the effort was directed toward forming titanium (e.g., 6Al-4V, 15V-3Cr-3Sn-3Al). Several DOE (i.e., Design of Experiment) techniques were employed during development and a Neural Net Computer Model was conceived for process control. This program was a joint effort in cooperation with the American Welding Society under contract with the Defense Advanced Research Projects Agency (DARPA). A synopsis of the laser forming process development, future opportunities, and applications are presented.

  18. Normal psychomotor development.

    PubMed

    Cioni, Giovanni; Sgandurra, Giuseppina

    2013-01-01

    "Psychomotor" development refers to changes in a child's cognitive, emotional, motor, and social capacities from the beginning of life throughout fetal and neonatal periods, infancy, childhood, and adolescence. It occurs in a variety of domains and a wide range of theories makes understanding children's development a challenging undertaking. Different models have tried to interpret the origins of human behavior, the pattern of developmental changes over time, and the individual and contextual factors that could direct child development. No single theory has been able to account for all aspects of child development, but each of them may contribute an important piece to the child development puzzle. Although theories sometimes disagree, much of their information is complementary rather than contradictory. The knowledge of child typical development and related theories and models is greatly useful for clinical practice, leading to recognition of developmental disorders and the ways in which they can be approached and treated. In this chapter, traditional and more modern concepts around functional development of psychomotor abilities are reported, firstly more in general and then specifically in the motor domain. PMID:23622146

  19. Developing Astronomy in Cuba

    NASA Astrophysics Data System (ADS)

    Rodriguez Taboada, R. E.

    2006-08-01

    Introduction Beginning from a brief historical introduction the up to day situation is presented and the topics relevant to Astronomy development analyzed from the view point of a person actually working in Astrophysics. Arising from national needs, Astronomical Calculations is the only "native-born" branch of astronomy in Cuba. Cuba was an observational platform capable to provide the Soviet Union with the 24 hours solar patrol needed by its Space Agency System to protect the men in orbit. This was the beginning of a very fruitful development of solar research in Cuba. Russia installed the instruments, trained the people to operate them, and gives the academic environment to develop the scientific work in solar physics, space weather, and related topics. What about Stellar Astronomy? The Cuban astro-climate is not good to develop an observational base. We are trying to develop stellar astronomy in collaboration with institutions capable to provide both, the academic and technical environment; but to continue developing Stellar Astronomy we need to influence the public opinion and convince people they need groups working in Astronomy. How to do that? Publishing. Giving conferences talking about OUR work, not only like spectators of the science. Showing science is culture in modern times. Showing projects in Astronomy can be cheap. ¡This is very important! Astronomy is not a luxury. Real possibilities I consider the Virtual Observatory concept the more appropriate in the near future, but it is necessary to have a connectivity level that is not commonly provided in Cuba, and to train the people. Concluding remarks From my experience "engagement" is the key word for Astronomy development in developing countries. Astronomy can not be developed without an appropriate academic environment, and we have not it. It is not "only" about financial resources, it is about "real collaboration" with a mature partner and common research goals.

  20. Space station structures development

    NASA Technical Reports Server (NTRS)

    Teller, V. B.

    1986-01-01

    A study of three interrelated tasks focusing on deployable Space Station truss structures is discussed. Task 1, the development of an alternate deployment system for linear truss, resulted in the preliminary design of an in-space reloadable linear motor deployer. Task 2, advanced composites deployable truss development, resulted in the testing and evaluation of composite materials for struts used in a deployable linear truss. Task 3, assembly of structures in space/erectable structures, resulted in the preliminary design of Space Station pressurized module support structures. An independent, redundant support system was developed for the common United States modules.

  1. Speakeasy software development

    NASA Astrophysics Data System (ADS)

    Baskinger, Patricia J.; Ozarow, Larry; Chruscicki, Mary C.

    1993-08-01

    The Speakeasy Software Development Project had three primary objectives. The first objective was to perform Independent Verification and Validation (IV & V) of the software and documentation associated with the signal processor being developed by Hazeltine and TRW under the Speakeasy program. The IV & V task also included an analysis and assessment of the ability of the signal processor software to provide LPI communications functions. The second objective was to assist in the enhancement and modification of an existing Rome Lab signal processor workstation. Finally, TASC developed project management support tools and provided program management support to the Speakeasy Program Office.

  2. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes. PMID:26395141

  3. Furlable spacecraft antenna development

    NASA Technical Reports Server (NTRS)

    Oliver, R. E.; Wilson, A. H.

    1972-01-01

    The development of large furlable spacecraft antennas using conical main reflectors is described. Two basic antenna configurations which utilize conical main reflectors have been conceived and are under development. In the conical-Gregorian configuration each ray experiences two reflections in traveling from the feed center to the aperture plane. In the Quadreflex (four reflection) configuration, each ray experiences four reflections, one at each of two subreflector surfaces and two at the main conical reflector surface. The RF gain measurements obtained from 6-ft and 30-in. models of the conical-Gregorian and Quadreflex concepts respectively were sufficiently encouraging to warrant further development of the concepts.

  4. Neutral beam development plan

    SciTech Connect

    Staten, H S

    1980-08-01

    The national plan is presented for developing advanced injection systems for use on upgrades of existing experiments, and use on future facilities such as ETF, to be built in the late 1980's or early 90's where power production from magnetic fusion will move closer to a reality. Not only must higher power and longer pulse length systems be developed , but they must operate reliably; they must be a tool for the experimenter, not the experiment itself. Neutral beam systems handle large amounts of energy and as such, they often are as complicated as the plasma physics experiment itself. This presents a significant challenge to the neutral beam developer.

  5. Microsystem product development.

    SciTech Connect

    Polosky, Marc A.; Garcia, Ernest J.

    2006-04-01

    Over the last decade the successful design and fabrication of complex MEMS (MicroElectroMechanical Systems), optical circuits and ASICs have been demonstrated. Packaging and integration processes have lagged behind MEMS research but are rapidly maturing. As packaging processes evolve, a new challenge presents itself, microsystem product development. Product development entails the maturation of the design and all the processes needed to successfully produce a product. Elements such as tooling design, fixtures, gages, testers, inspection, work instructions, process planning, etc., are often overlooked as MEMS engineers concentrate on design, fabrication and packaging processes. Thorough, up-front planning of product development efforts is crucial to the success of any project.

  6. Democracy and economic development.

    PubMed

    Rao, V

    1985-01-01

    This discussion explains why democracy as is generally understood may not be suitable to meet the challenges of a developing economy and how democratic institutions generally fail to respond to the immediate demands of a population impatient to raise its level of living. It defines the terms economic development and democracy, reviews some theoretical models of democracy which have been proposed in economic theory, proposes an approach to the process of economic development, and considers problems of development. Economic development is a process which calls for huge investments in personnel and material. Such investment programs imply cuts in current consumption that would be painful at the low levels of living that exist in almost all developing societies. Governments need to resort to strong measures, and they must enforce them vigorously in order to marshal the surpluses required for investment. If such measures were put to a popular vote, they would certainly be defeated. Mainstream economic theory assumes the virtues of a market system and the decisions arrived at by the interaction of market forces. This is the economic equivalent of democracy. Yet, mainstream economic theory devotes little attention to the conditions under which a market system generates a just solution. The democratic developing countries have all inherited a class society, with a highly skewed distribution of income. The wealthy minority often seeks to preserve its privileged position and to enjoy the benefits of development. It even seeks the help of the judiciary to preserve the sanctity of private property and to assure that its patterns of conspicuous consumption can continue. This is done in the name of democratic rights. Many developing societies are burdened with outmoded traditions and value systems that are incompatible with the production relations of the new society they hope to achieve. The international exchange of resources is believed by some to be an attempt to control the

  7. CNS development: an overview

    NASA Technical Reports Server (NTRS)

    Nowakowski, R. S.; Hayes, N. L.

    1999-01-01

    The basic principles of the development of the central nervous system (CNS) are reviewed, and their implications for both normal and abnormal development of the brain are discussed. The goals of this review are (a) to provide a set of concepts to aid in understanding the variety of complex processes that occur during CNS development, (b) to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and (c) to provide a basis for understanding how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

  8. Textile technology development

    NASA Technical Reports Server (NTRS)

    Shah, Bharat M.

    1995-01-01

    The objectives of this report were to evaluate and select resin systems for Resin Transfer Molding (RTM) and Powder Towpreg Material, to develop and evaluate advanced textile processes by comparing 2-D and 3-D braiding for fuselage frame applications and develop window belt and side panel structural design concepts, to evaluate textile material properties, and to develop low cost manufacturing and tooling processes for the automated manufacturing of fuselage primary structures. This research was in support of the NASA and Langley Research Center (LaRc) Advanced Composite Structural Concepts and Materials Technologies for Primary Aircraft Structures program.

  9. Crew procedures development techniques

    NASA Technical Reports Server (NTRS)

    Arbet, J. D.; Benbow, R. L.; Hawk, M. L.; Mangiaracina, A. A.; Mcgavern, J. L.; Spangler, M. C.

    1975-01-01

    The study developed requirements, designed, developed, checked out and demonstrated the Procedures Generation Program (PGP). The PGP is a digital computer program which provides a computerized means of developing flight crew procedures based on crew action in the shuttle procedures simulator. In addition, it provides a real time display of procedures, difference procedures, performance data and performance evaluation data. Reconstruction of displays is possible post-run. Data may be copied, stored on magnetic tape and transferred to the document processor for editing and documentation distribution.

  10. Thermal Protection Materials Development

    NASA Technical Reports Server (NTRS)

    Selvaduray, Guna; Cox, Michael

    1998-01-01

    The main portion of this contract year was spent on the development of materials for high temperature applications. In particular, thermal protection materials were constantly tested and evaluated for thermal shock resistance, high-temperature dimensional stability, and tolerance to hostile environmental effects. The analytical laboratory at the Thermal Protection Materials Branch (TPMB), NASA-Ames played an integral part in the process of materials development of high temperature aerospace applications. The materials development focused mainly on the determination of physical and chemical characteristics of specimens from the various research programs.

  11. Imaging in drug development.

    PubMed

    Nairne, James; Iveson, Peter B; Meijer, Andreas

    2015-01-01

    Imaging has played an important part in the diagnosis of disease and development of the understanding of the underlying disease mechanisms and is now poised to make an impact in the development of new pharmaceuticals. This chapter discusses the underlying technologies that make the field ready for this challenge. In particular, the potentials of magnetic resonance imaging and functional magnetic resonance imaging are outlined, including the new methods developed to provide additional information from the scans carried out. The field of nuclear medicine has seen a rapid increase in interest as advances in radiochemistry have enabled a wide range of new radiotracers to be synthesised. PMID:25727706

  12. Advanced Hydrogen Turbine Development

    SciTech Connect

    Marra, John

    2015-09-30

    Under the sponsorship of the U.S. Department of Energy (DOE) National Energy Technology Laboratories, Siemens has completed the Advanced Hydrogen Turbine Development Program to develop an advanced gas turbine for incorporation into future coal-based Integrated Gasification Combined Cycle (IGCC) plants. All the scheduled DOE Milestones were completed and significant technical progress was made in the development of new technologies and concepts. Advanced computer simulations and modeling, as well as subscale, full scale laboratory, rig and engine testing were utilized to evaluate and select concepts for further development. Program Requirements of: A 3 to 5 percentage point improvement in overall plant combined cycle efficiency when compared to the reference baseline plant; 20 to 30 percent reduction in overall plant capital cost when compared to the reference baseline plant; and NOx emissions of 2 PPM out of the stack. were all met. The program was completed on schedule and within the allotted budget

  13. NASA Balloon Technology Developments

    NASA Technical Reports Server (NTRS)

    Fairbrother, D. A.

    2004-01-01

    The National Aeronautics and Space Administration (NASA) Balloon Program has been, and will continue to be, committed to improving the capabilities of balloons to support science missions. Fundamental to vehicle improvement is a program of technology development that will enable improved flight performance throughout the next decade. The program s technology thrust areas include: materials, vehicle design & development, structural analysis, operations & support systems, performance modeling and planetary balloons. Building on the foundations of the 18-year research and development program, a technology roadmap has been generated which identifies specific areas of interest to NASA and the vision of future developments. The major components of the roadmap are: vehicle systems, balloon-craft systems, operational and safety support systems, and planetary vehicles. Current technology activities include nanocomposite balloon films, a new balloon designed to lift 3600 kgs to 36 km, a balloon rotation rate study and Mars pumpkin balloon investigations. The technology roadmap, as well as specific projects and recent advancements, will be presented.

  14. NASA balloon technology developments

    NASA Astrophysics Data System (ADS)

    Fairbrother, D. A.

    The National Aeronautics and Space Administration (NASA) Balloon Program has been, and will continue to be, committed to improving the capabilities of balloons to support science missions. Fundamental to vehicle improvement is a program of technology development that will enable improved flight performance throughout the next decade. The program's technology thrust areas include: materials, vehicle design & development, structural analysis, operations & support systems, performance modeling and planetary balloons. Building on the foundations of the 18-year research and development program, a technology roadmap has been generated which identifies specific areas of interest to NASA and the vision of future developments. The major components of the roadmap are: vehicle systems, ballooncraft systems, operational and safety support systems, and planetary vehicles. Current technology activities include nanocomposite balloon films, a new balloon designed to lift 3600 kgs to 36 km, a balloon rotation rate study and Mars pumpkin balloon investigations. The technology roadmap, as well as specific projects and recent advancements, will be presented.

  15. Implications for Development Communications.

    ERIC Educational Resources Information Center

    Hudson, Heather E.

    1979-01-01

    Outlines issues that could affect the opportunities of developing countries to take advantage of the benefits of communication technology. Discusses the allocation of the frequency spectrum and the use of satellite technology. (JMF)

  16. REGIONAL MANUFACTURING TECHNICAL DEVELOPMENT

    SciTech Connect

    EASON, H.A.

    1997-02-21

    This project covers four CRADAS (Cooperative Research and Development Agreements) which were initiated in 1991 and 1993. The two CRADAS with the state of Tennessee and the state of Florida were to provide technical assistance to small manufacturers in those states and the CRADA with the Tennessee Technology Foundation was to engage in joint economic development activities within the state. These three CRADAS do not fit the traditional definition of CRADAS and would be administered by other agreement mechanisms, today. But in these early days of technology transfer efforts, the CRADA mechanism was already developed and usable. The CRADA with Coors Ceramics is a good example of a CRADA and was used to develop nondestructive testing technology for ceramic component inspection. The report describes the background of this project, its economic impact, and its benefits to the U. S. Department of Energy.

  17. Element-ary Development.

    ERIC Educational Resources Information Center

    Schamp, Homer W., Jr.

    1989-01-01

    Describes the historic development of the periodic table from the four-element theory to the Lavoisier's table. Presents a table listing the old and new names of chemicals and the Lavoisier's table of elements. Lists two references. (YP)

  18. NASA DEVELOP students

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA DEVELOP students at Stennis Space Center recently held a midterm review with George Crozier, who serves as a science adviser to the team. The team also was joined by Jamie Favors of the Mobile (Ala.) County Health Department DEVELOP Team; Cheri Miller, the team's NASA adviser; and Kenton Ross, a team science adviser. Students participating in the meeting included: Lauren Childs, Jason Jones, Maddie Brozen, Matt Batina, Jenn Frey, Angie Maki and Aaron Brooks. The primary purpose of the meeting was to update Crozier on the status of the team's work for the summer 2008 term and discuss plans for the fiscal year 2009 project proposal. This included discussion of a possible project to study the effects of hurricanes on the Florida panhandle. DEVELOP is a NASA-sponsored, student-led, student-run program focused on developing projects to help communities.

  19. Toddler development (image)

    MedlinePlus

    The range of toddler development is from 1 to 3 years of age. Toddler safety is very important during this time since more accidents occur during toddler years than at any other stage of childhood. ...

  20. Space Development Grid Portal

    NASA Technical Reports Server (NTRS)

    Vaziri, Arsi

    2004-01-01

    This viewgraph presentation provides information on the development of a portal to provide secure and distributed grid computing for Payload Operations Integrated Center and Mission Control Center ground services.

  1. Patterns of Gender Development

    PubMed Central

    Martin, Carol Lynn; Ruble, Diane N.

    2013-01-01

    A comprehensive theory of gender development must describe and explain long-term developmental patterning and changes and how gender is experienced in the short term. This review considers multiple views on gender patterning, illustrated with contemporary research. First, because developmental research involves understanding normative patterns of change with age, several theoretically important topics illustrate gender development: how children come to recognize gender distinctions and understand stereotypes, and the emergence of prejudice and sexism. Second, developmental researchers study the stability of individual differences over time, which elucidates developmental processes. We review stability in two domains—sex segregation and activities/interests. Finally, a new approach advances understanding of developmental patterns, based on dynamic systems theory. Dynamic systems theory is a metatheoretical framework for studying stability and change, which developed from the study of complex and nonlinear systems in physics and mathematics. Some major features and examples show how dynamic approaches have been and could be applied in studying gender development. PMID:19575615

  2. Gravity and embryonic development

    NASA Technical Reports Server (NTRS)

    Young, R. S.

    1976-01-01

    The relationship between the developing embryo (both plant and animal) and a gravitational field has long been contemplated. The difficulty in designing critical experiments on the surface of the earth because of its background of 1 g, has been an obstacle to a resolution of the problem. Biological responses to gravity (particularly in plants) are obvious in many cases; however, the influence of gravity as an environmental input to the developing embryo is not as obvious and has proven to be extremely difficult to define. In spite of this, over the years numerous attempts have been made using a variety of embryonic materials to come to grips with the role of gravity in development. Three research tools are available: the centrifuge, the clinostat, and the orbiting spacecraft. Experimental results are now available from all three sources. Some tenuous conclusions are drawn, and an attempt at a unifying theory of gravitational influence on embryonic development is made.

  3. How Leaders Develop Leaders.

    ERIC Educational Resources Information Center

    Cohen, Eli; Tichy, Noel

    1997-01-01

    Effective leaders who have been instrumental in their companies' success must contribute to continuing success by personally developing leaders at all levels. They should share their teachable point of view, including ideas, values, edge, and energy. (JOW)

  4. ECOSYSTEM GROWTH AND DEVELOPMENT

    EPA Science Inventory

    Thermodynamically, ecosystem growth and development is the process by which energy throughflow and stored biomass increase. Several proposed hypotheses describe the natural tendencies that occur as an ecosystem matures, and here, we consider five: minimum entropy production, maxi...

  5. FPG Child Development Institute

    MedlinePlus

    ... an aRPy Ambassador Ohio University News More Featured Projects National Center for Early Childhood Development, Teaching, and ... for the Educare Learning Network Implementation Study This project consists of planning and implementing an evaluation of ...

  6. Entry signals control development

    PubMed Central

    Dinman, Jonathan D.

    2015-01-01

    Certain structural elements allow messenger RNAs not usually processed by the protein-synthesis apparatus to be translated. It now seems that they also control the expression of genes involved in embryonic development. See Article p.33 PMID:25409148

  7. New developments at BIONET.

    PubMed Central

    Roode, D; Liebschutz, R; Maulik, S; Friedemann, T; Benton, D; Kristofferson, D

    1988-01-01

    BIONET has made considerable progress in developing communication links among molecular biologists and biochemists worldwide. We describe these efforts and also note the many new enhancements to the BIONET system itself. PMID:3353224

  8. Nurturing Intellectual Development.

    ERIC Educational Resources Information Center

    Woods, Donald R.

    1990-01-01

    The use of taxonomic scales to assess the level of student cognitive development and thinking skills, and to structure instruction is discussed. One instructor's method is presented. Perry's taxonomy is graphically illustrated. Sources for five assessment instruments are listed. (CW)

  9. Mission critical technology development

    NASA Technical Reports Server (NTRS)

    Sliwa, Nancy

    1991-01-01

    Mission critical technology development is presented in the form of the viewgraphs. The following subject areas are covered: organization/philosophy overview; fault management technology; and introduction to optical processing.

  10. JPRS report, nuclear developments

    SciTech Connect

    1991-03-28

    This report contains articles concerning the nuclear developments of the following countries: (1) China; (2) Japan, North Korea, South Korea; (3) Bulgaria; (4) Argentina, Brazil, Honduras; (5) India, Iran, Pakistan, Syria; (6) Soviet Union; and (7) France, Germany, Turkey.

  11. Cascade Distillation System Development

    NASA Technical Reports Server (NTRS)

    Callahan, Michael R.; Sargushingh, Miriam; Shull, Sarah

    2014-01-01

    NASA's Advanced Exploration Systems (AES) Life Support System (LSS) Project is chartered with de-veloping advanced life support systems that will ena-ble NASA human exploration beyond low Earth orbit (LEO). The goal of AES is to increase the affordabil-ity of long-duration life support missions, and to re-duce the risk associated with integrating and infusing new enabling technologies required to ensure mission success. Because of the robust nature of distillation systems, the AES LSS Project is pursuing develop-ment of the Cascade Distillation Subsystem (CDS) as part of its technology portfolio. Currently, the system is being developed into a flight forward Generation 2.0 design.

  12. Infant - newborn development

    MedlinePlus

    ... holding a hand; may take few steps alone SENSORY DEVELOPMENT Hearing, begins before birth, and is mature at birth. The infant prefers the human voice. Touch, taste, and smell, mature at birth; ...

  13. Developing Friendship and Intimacy.

    ERIC Educational Resources Information Center

    Maslow, Abraham H.

    1991-01-01

    Presents previously unpublished paper written by Abraham Maslow in April 1968 in which Maslow speculates on the issue that society had become pathologically individualistic and needed to develop better means of facilitating close relationships among people. (Author/ABL)

  14. Advanced Interconnect Development

    SciTech Connect

    Yang, Z.G.; Maupin, G.; Simner, S.; Singh, P.; Stevenson, J.; Xia, G.

    2005-01-27

    The objectives of this project are to develop cost-effective, optimized materials for intermediate temperature SOFC interconnect and interconnect/electrode interface applications and identify and understand degradation processes in interconnects and at their interfaces with electrodes.

  15. Fetal Health and Development

    MedlinePlus

    ... fetus grows and develops. There are specific prenatal tests to monitor both the mother's health and fetal health during each trimester. With modern technology, health professionals can Detect birth defects Identify problems ...

  16. Child Development & Behavior Topics

    MedlinePlus

    ... Children about September 11th Talking to Kids about War and Terrorism Tantrums: Behavior Problems Tantrums Podcast Teen ... Video Games Back to top W Walking Safety Water and Pool Safety Welcome to Your Child: Development ...

  17. Fiber Optics Instrumentation Development

    NASA Technical Reports Server (NTRS)

    Chan, Patrick Hon Man; Parker, Allen R., Jr.; Richards, W. Lance

    2010-01-01

    This is a general presentation of fiber optics instrumentation development work being conducted at NASA Dryden for the past 10 years and recent achievements in the field of fiber optics strain sensors.

  18. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  19. Initial Hardware Development Schedule

    NASA Technical Reports Server (NTRS)

    Culpepper, William X.

    1991-01-01

    The hardware development schedule for the Common Lunar Lander's (CLLs) tracking system is presented. Among the topics covered are the following: historical perspective, solution options, industry contacts, and the rationale for selection.

  20. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742