Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

PubMed

Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

2011-03-01

In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency

PubMed Central

Hannibal, Luciana; Lysne, Vegard; Bjørke-Monsen, Anne-Lise; Behringer, Sidney; Grünert, Sarah C.; Spiekerkoetter, Ute; Jacobsen, Donald W.; Blom, Henk J.

2016-01-01

Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status. Clinically, vitamin B12 deficiency leads to neurological deterioration and megaloblastic anemia, and, if left untreated, to death. Subclinical vitamin B12 deficiency (usually defined as a total serum B12 of <200 pmol/L) presents asymptomatically or with rather subtle generic symptoms that oftentimes are mistakenly ascribed to unrelated disorders. Numerous studies have now established that serum vitamin B12 has limited diagnostic value as a stand-alone marker. Low serum levels of vitamin B12 not always represent deficiency, and likewise, severe functional deficiency of the micronutrient has been documented in the presence of normal and even high levels of serum vitamin B12. This review discusses the usefulness and limitations of current biomarkers of B12 status in newborn screening, infant and adult diagnostics, the algorithms utilized to diagnose B12 deficiency and unusual findings of vitamin B12 status in various human disorders. PMID:27446930

Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency.

PubMed

Hannibal, Luciana; Lysne, Vegard; Bjørke-Monsen, Anne-Lise; Behringer, Sidney; Grünert, Sarah C; Spiekerkoetter, Ute; Jacobsen, Donald W; Blom, Henk J

2016-01-01

Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status. Clinically, vitamin B12 deficiency leads to neurological deterioration and megaloblastic anemia, and, if left untreated, to death. Subclinical vitamin B12 deficiency (usually defined as a total serum B12 of <200 pmol/L) presents asymptomatically or with rather subtle generic symptoms that oftentimes are mistakenly ascribed to unrelated disorders. Numerous studies have now established that serum vitamin B12 has limited diagnostic value as a stand-alone marker. Low serum levels of vitamin B12 not always represent deficiency, and likewise, severe functional deficiency of the micronutrient has been documented in the presence of normal and even high levels of serum vitamin B12. This review discusses the usefulness and limitations of current biomarkers of B12 status in newborn screening, infant and adult diagnostics, the algorithms utilized to diagnose B12 deficiency and unusual findings of vitamin B12 status in various human disorders.

Causes of vitamin B12 and folate deficiency.

PubMed

Allen, Lindsay H

2008-06-01

This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.

Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

PubMed

Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

2015-08-01

Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing

PubMed Central

Porter, Kirsty; Hoey, Leane; Hughes, Catherine F.; Ward, Mary; McNulty, Helene

2016-01-01

The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications. PMID:27854316

Strain Background Modifies Phenotypes in the ATP8B1-Deficient Mouse

PubMed Central

Vargas, Julie C.; Xu, Hongmei; Groen, Annamiek; Paulusma, Coen C.; Grenert, James P.; Pawlikowska, Ludmila; Sen, Saunak; Elferink, Ronald P. J. Oude; Bull, Laura N.

2010-01-01

Background Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency. Methodology/Principal Findings We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains. Conclusions/Significance Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease. PMID:20126555

Rationalising vitamin B6 biofortification in crop plants.

PubMed

Fudge, Jared; Mangel, Nathalie; Gruissem, Wilhelm; Vanderschuren, Hervé; Fitzpatrick, Teresa B

2017-04-01

Vitamin B 6 encompasses a group of related compounds (vitamers) that can only be biosynthesised de novo by plants and microorganisms. Enzymatic cofactor and antioxidant functions for vitamin B 6 are established in all kingdoms. Human vitamin B 6 dietary insufficiency or genetic defects in B 6 vitamer interconversion result in various neurological and inflammatory pathologies with several populations at-risk or marginal for vitamin B 6 status. Three (rice, wheat and cassava) of the world's top five staple crops do not meet the recommended dietary allowance for vitamin B 6 , when consumed as a major proportion of the diet. In addition, controlled enhancement of the appropriate B 6 vitamer in crops has the potential to confer stress resistance. Thus, crop biofortification strategies represent an opportunity to reduce the risk of deficiency in populations with limited diet diversity and quality, as well as improving stress tolerance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress

PubMed Central

Havaux, Michel; Ksas, Brigitte; Szewczyk, Agnieszka; Rumeau, Dominique; Franck, Fabrice; Caffarri, Stefano; Triantaphylidès, Christian

2009-01-01

Background Vitamin B6 is a collective term for a group of six interconvertible compounds: pyridoxine, pyridoxal, pyridoxamine and their phosphorylated derivatives. Vitamin B6 plays essential roles as a cofactor in a range of biochemical reactions. In addition, vitamin B6 is able to quench reactive oxygen species in vitro, and exogenously applied vitamin B6 protects plant cells against cell death induced by singlet oxygen (1O2). These results raise the important question as to whether plants employ vitamin B6 as an antioxidant to protect themselves against reactive oxygen species. Results The pdx1.3 mutation affects the vitamin B6 biosynthesis enzyme, pyridoxal synthase (PDX1), and leads to a reduction of the vitamin B6 concentration in Arabidopsis thaliana leaves. Although leaves of the pdx1.3 Arabidopsis mutant contained less chlorophyll than wild-type leaves, we found that vitamin B6 deficiency did not significantly impact photosynthetic performance or shoot and root growth. Chlorophyll loss was associated with an increase in the chlorophyll a/b ratio and a selective decrease in the abundance of several PSII antenna proteins (Lhcb1/2, Lhcb6). These changes were strongly dependent on light intensity, with high light amplifying the difference between pdx1.3 and the wild type. When leaf discs were exposed to exogenous 1O2, lipid peroxidation in pdx1.3 was increased relative to the wild type; this effect was not observed with superoxide or hydrogen peroxide. When leaf discs or whole plants were exposed to excess light energy, 1O2-mediated lipid peroxidation was enhanced in leaves of the pdx1.3 mutant relative to the wild type. High light also caused an increased level of 1O2 in vitamin B6-deficient leaves. Combining the pdx1.3 mutation with mutations affecting the level of 'classical' quenchers of 1O2 (zeaxanthin, tocopherols) resulted in a highly photosensitive phenotype. Conclusion This study demonstrates that vitamin B6 has a function in the in vivo antioxidant

Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development.

PubMed

Beutler, Ernest; Duparc, Stephan

2007-10-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.

B vitamin status, dietary intake and length of stay in a sample of elderly rehabilitation patients.

PubMed

O'Leary, F; Flood, V M; Petocz, P; Allman-Farinelli, M; Samman, S

2011-06-01

To investigate the relationships between previous diet, biomarkers of selected B vitamins, nutritional status and length of stay. Cross sectional study. Geriatric rehabilitation patients, Sydney, Australia. Fifty two consenting patients with normal serum creatinine levels and no dementia. Serum vitamin B12, plasma vitamin B6, serum and erythrocyte folate, homocysteine and methylmalonic acid (MMA) concentrations; dietary intake using a validated semi-quantitative food frequency questionnaire and nutritional assessment using the Mini Nutritional Assessment (MNA). Length of stay data were collected from medical records after discharge. The age was 80 ± 8 year (mean ± SD), BMI 26.4 ± 6.8 kg/m2 and MNA score 22 ± 3 indicating some risk of malnutrition. Deficiencies of vitamins B6, B12 and folate were found in 30, 22 and 5 subjects respectively. Length of stay was positively correlated with age and MMA (Spearman's correlation 0.4, p<0.01 and 0.28, p<0.05 respectively) and negatively correlated with albumin, vitamin B6 and MNA score (Spearman's correlation -0.35, -0.33 and -0.29, p<0.05). After adjustment for age and sex, ln vitamin B6 and ln MMA concentrations were significant in predicting ln LOS (p=0.006 and p=0.014 respectively). The study indicates a high risk of vitamin B deficiencies in the elderly and suggests that deficiencies of vitamins B6 and B12 are associated with length of stay. This is concerning as B vitamin status is rarely fully assessed.

Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients.

PubMed

Compher, Charlene W; Kinosian, Bruce P; Stoner, Nancy E; Lentine, Deborah C; Buzby, Gordon P

2002-01-01

Choline has recently been recognized as an essential nutrient, in part based on deficiency data in long-term home total parenteral nutrition (TPN) patients. Choline, a methyl donor in the metabolism of homocysteine, is intricately related to folate status, but little is known about choline and vitamin B12 status. Long-term TPN patients are also subject to vitamin B12 deficiency. The objective of the study was to evaluate any interaction between choline, vitamin B12, and folate in patients with severe malabsorption syndromes, requiring long-term TPN. Plasma free choline, serum and red blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma total homocysteine concentrations were assayed by standard methods. Low choline was defined as values that fall 1 to < or =3 and marked low choline concentration as >3 SD below the control mean. Both low choline concentrations (52% were marked low, 33% low, 14% normal) and elevated methylmalonic acid concentrations (47%) were prevalent. Choline concentration was significantly lower and RBC folate higher in patients with elevated methylmalonic acid. Total homocysteine elevations were rare (3 of 21) and mild. These data suggest a strong interaction between vitamin B12 and choline deficiencies and folate status in this population, which may be due in part to variations in vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid metabolism. Choline use may also increase, and choline deficiency may worsen if choline substitutes when the vitamin B12 side of the homocysteine metabolic pathway cannot be used.

Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring.

PubMed

Almeida, Mara Ribeiro; Mabasa, Lawrence; Crane, Courtney; Park, Chung S; Venâncio, Vinícius Paula; Bianchi, Maria Lourdes Pires; Antunes, Lusânia Maria Greggi

2016-07-01

Vitamin B6 plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring. Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B6 supplementation or deficiency did not change hippocampal global DNA methylation. A maternal vitamin B6 -deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial.

PubMed

Naik, Sadanand; Bhide, Vijayshri; Babhulkar, Ashish; Mahalle, Namita; Parab, Sonali; Thakre, Ravi; Kulkarni, Mohan

2013-10-09

Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 × 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 μ mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12

Vitamin B12 deficiency: Characterization of psychometrics and MRI morphometrics.

PubMed

Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Tu, Min-Chien

2016-01-01

Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations. We compared 34 consecutive patients with vitamin B12 deficiency (serum level ≤ 250 pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed. The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P < 0.05), language (P < 0.01), orientation (P < 0.01), and mental manipulation (P < 0.05). The patients also showed a greater frontal horn ratio than the controls (P < 0.05). Bicaudate ratio, fronto-occipital ratio, uncotemporal index, and normalized interuncal distance all showed a strong correlation with the total score of MMSE and CASI (all P < 0.01). Among these psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P < 0.01). Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying

Glucose-6-Phosphate Dehydrogenase Deficiency in Nigerian Children

PubMed Central

Williams, Olatundun; Gbadero, Daniel; Edowhorhu, Grace; Brearley, Ann; Slusher, Tina; Lund, Troy C.

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4±3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p = 0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p = 0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p = 0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection. PMID:23874768

Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

PubMed

Williams, Olatundun; Gbadero, Daniel; Edowhorhu, Grace; Brearley, Ann; Slusher, Tina; Lund, Troy C

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

B-vitamin deficiency is protective against DSS-induced colitis in mice

PubMed Central

Benight, Nancy M.; Stoll, Barbara; Chacko, Shaji; da Silva, Vanessa R.; Marini, Juan C.; Gregory, Jesse F.; Stabler, Sally P.

2011-01-01

Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B6-B12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-13C-methyl-2H3]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-α and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B6, as markers of B12 function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B6 deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B6 deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology. PMID:21596995

Impaired functional vitamin B6 status is associated with increased risk of lung cancer.

PubMed

Theofylaktopoulou, Despoina; Midttun, Øivind; Ueland, Per M; Meyer, Klaus; Fanidi, Anouar; Zheng, Wei; Shu, Xiao-Ou; Xiang, Yong-Bing; Prentice, Ross; Pettinger, Mary; Thomson, Cynthia A; Giles, Graham G; Hodge, Allison; Cai, Qiuyin; Blot, William J; Wu, Jie; Johansson, Mikael; Hultdin, Johan; Grankvist, Kjell; Stevens, Victoria L; McCullough, Marjorie M; Weinstein, Stephanie J; Albanes, Demetrius; Ziegler, Regina; Freedman, Neal D; Langhammer, Arnulf; Hveem, Kristian; Naess, Marit; Sesso, Howard D; Gaziano, J Michael; Buring, Julie E; Lee, I-Min; Severi, Gianluca; Zhang, Xuehong; Stampfer, Meir J; Han, Jiali; Smith-Warner, Stephanie A; Zeleniuch-Jacquotte, Anne; Le Marchand, Loic; Yuan, Jian-Min; Wang, Renwei; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Rothman, Nathaniel; Ericson, Ulrika; Sonestedt, Emily; Visvanathan, Kala; Jones, Miranda R; Relton, Caroline; Brennan, Paul; Johansson, Mattias; Ulvik, Arve

2018-06-15

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR 4th vs. 1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status. © 2017 UICC.

Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss.

PubMed

Ronnenberg, Alayne G; Venners, Scott A; Xu, Xiping; Chen, Changzhong; Wang, Lihua; Guang, Wenwei; Huang, Aiqun; Wang, Xiaobin

2007-08-01

Maternal vitamin status contributes to clinical spontaneous abortion, but the role of B-vitamin and homocysteine status in subclinical early pregnancy loss is unknown. Three-hundred sixty-four textile workers from Anqing, China, who conceived at least once during prospective observation (1996-1998), provided daily urine specimens for up to 1 year, and urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy loss. Homocysteine, folate, and vitamins B6 and B12 were measured in preconception plasma. Relative to women in the lowest quartile of vitamin B6, those in the third and fourth quartiles had higher adjusted proportional hazard ratios of conception (hazard ratio (HR)=2.2, 95% confidence interval (CI): 1.3, 3.4; HR=1.6, 95% CI: 1.1, 2.3, respectively), and the adjusted odds ratio for early pregnancy loss in conceptive cycles was lower in the fourth quartile (odds ratio=0.5, 95% CI: 0.3, 1.0). Women with sufficient vitamin B6 had a higher adjusted hazard ratio of conception (HR=1.4, 95% CI: 1.1, 1.9) and a lower adjusted odds ratio of early pregnancy loss in conceptive cycles (odds ratio=0.7, 95% CI: 0.4, 1.1) than did women with vitamin B6 deficiency. Poor vitamin B6 status appears to decrease the probability of conception and to contribute to the risk of early pregnancy loss in this population.

Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.

PubMed

Gregory, Jesse F; DeRatt, Barbara N; Rios-Avila, Luisa; Ralat, Maria; Stacpoole, Peter W

2016-07-01

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812. Copyright © 2016 Elsevier B.V. and Société Fran

Subtle abnormalities of gait detected early in vitamin B6 deficiency in aged and weanling rats with hind leg gait analysis.

PubMed

Schaeffer, M C; Cochary, E F; Sadowski, J A

1990-04-01

Motor abnormalities have been observed in every species made vitamin B6 deficient, and have been detected and quantified early in vitamin B6 deficiency in young adult female Long-Evans rats with hind leg gait analysis. Our objective was to determine if hind leg gait analysis could be used to detect vitamin B6 deficiency in weanling (3 weeks) and aged (23 months) Fischer 344 male rats. Rats (n = 10 per group) were fed: the control diet ad libitum (AL-CON); the control diet devoid of added pyridoxine hydrochloride (DEF); or the control diet pair-fed to DEF (PF-CON). At 10 weeks, plasma pyridoxal phosphate concentration confirmed deficiency in both age groups. Gait abnormalities were detected in the absence of gross motor disturbances in both aged and weanling DEF rats at 2-3 weeks. Width of step was significantly reduced (16%, p less than 0.003) in DEF aged rats compared to AL- and PF-CON. This pattern of response was similar to that reported previously in young adult rats. In weanling rats, pair feeding alone reduced mean width of step (+/- SEM) by 25% compared to ad libitum feeding (2.7 +/- 0.1 vs 3.6 +/- 0.1 cm for PF- vs AL-CON, respectively, p less than 0.05). In DEF weanling rats, width (3.0 +/- 0.1 cm) was increased compared to PF-CON (11%, p less than 0.05) but decreased compared to AL-CON (16%, p less than 0.05). Width of step was significantly altered early in B6 deficiency in rats of different ages and strains and in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Micronutrient Status among Pregnant Women in Zinder, Niger and Risk Factors Associated with Deficiency

PubMed Central

Wessells, K. Ryan; Ouédraogo, Césaire T.; Young, Rebecca R.; Faye, M. Thierno; Brito, Alex; Hess, Sonja Y.

2017-01-01

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages (n = 88) were included. Capillary and venous blood samples (n = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B12. C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (<15 µg/L) and sTfR (>8.3 mg/L), respectively. In total, 40.7% of women had low pZn (<50 µg/dL), 79.7% had marginal RBP (<1.32 µmol/L), 44.3% of women had low folate (<10 nmol/L) and 34.8% had low B12 concentrations (<148 pmol/L). Common risk factors associated with MN status included gravidity, mid-upper-arm circumference, geophagy, malaria, and result of the woman’s last pregnancy. Interventions to promote the strengthening of antenatal care, and access and adherence to nutrition and health interventions are critical among pregnant women in this population. PMID:28445440

Micronutrient Status among Pregnant Women in Zinder, Niger and Risk Factors Associated with Deficiency.

PubMed

Wessells, K Ryan; Ouédraogo, Césaire T; Young, Rebecca R; Faye, M Thierno; Brito, Alex; Hess, Sonja Y

2017-04-26

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages ( n = 88) were included. Capillary and venous blood samples ( n = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B 12 . C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (<15 µg/L) and sTfR (>8.3 mg/L), respectively. In total, 40.7% of women had low pZn (<50 µg/dL), 79.7% had marginal RBP (<1.32 µmol/L), 44.3% of women had low folate (<10 nmol/L) and 34.8% had low B 12 concentrations (<148 pmol/L). Common risk factors associated with MN status included gravidity, mid-upper-arm circumference, geophagy, malaria, and result of the woman's last pregnancy. Interventions to promote the strengthening of antenatal care, and access and adherence to nutrition and health interventions are critical among pregnant women in this population.

Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

PubMed

Pawlak, Roman

2015-06-01

The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Preconception folate and vitamin B(6) status and clinical spontaneous abortion in Chinese women.

PubMed

Ronnenberg, Alayne G; Goldman, Marlene B; Chen, Dafang; Aitken, Iain W; Willett, Walter C; Selhub, Jacob; Xu, Xiping

2002-07-01

To assess the association between preconception homocysteine and B vitamin status and risk of clinical spontaneous abortion in women from Anqing, China. All women were aged 21-34 years, had never smoked, and were primigravid. Patients (n = 49) were women with a clinically recognized pregnancy who experienced a fetal death before 100 days' gestation. Controls (n = 409) were women who maintained a pregnancy that ended in a live birth. Homocysteine, folate, and vitamins B(6) and B(12) concentrations were measured in plasma obtained before conception. Mean vitamin B(6) concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L, P =.04). In addition, the risk of spontaneous abortion tended to increase with decreasing plasma vitamin B(6) and folate concentration (P for trend =.06 and.07, respectively), although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of spontaneous abortion was four-fold higher among women with suboptimal plasma concentrations of both folate and vitamin B(6) (folate less than or equal to 8.4 nmol/L and vitamin B(6) less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1, 95% confidence interval 1.2, 14.4). Homocysteine and vitamin B(12) status were not associated with spontaneous abortion risk. Suboptimal preconception folate and vitamin B(6) status, especially when they occur together, may increase the risk of clinical spontaneous abortion. Additional prospective studies are needed to confirm these findings and to determine whether antenatal B vitamin supplementation reduces spontaneous abortion risk.

Vitamin B-12 Deficiency in Children Is Associated with Grade Repetition and School Absenteeism, Independent of Folate, Iron, Zinc, or Vitamin A Status Biomarkers.

PubMed

Duong, Minh-Cam; Mora-Plazas, Mercedes; Marín, Constanza; Villamor, Eduardo

2015-07-01

Micronutrients are essential to neurocognitive development; yet their role in educational outcomes is unclear. We examined the associations of micronutrient status biomarkers with the risk of grade repetition and rates of school absenteeism in a cohort of school children. We recruited 3156 children aged 5-12 y from public schools in Bogota, Colombia. Circulating ferritin, hemoglobin, zinc, vitamin A, and vitamin B-12; erythrocyte folate; and mean corpuscular volume (MCV) were measured in blood samples obtained at the beginning of the year. Absenteeism was recorded weekly during the school year, and grade repetition was determined the next year. Risk ratios for grade repetition and rate ratios for absenteeism were estimated by categories of micronutrient status indicators with use of Poisson regression, adjusting for potential confounders. The risk of grade repetition was 4.9%, and the absenteeism rate was 3.8 d per child-year of observation. Vitamin B-12 deficiency (<148 pmol/L) was associated with an adjusted 2.36-fold greater risk of grade repetition (95% CI: 1.03, 5.41; P = 0.04) compared with plasma concentrations ≥148 pmol/L. Other micronutrients were not related to grade repetition. Vitamin B-12 deficiency was also associated with school absenteeism rates. Compared with children with plasma vitamin B-12 concentrations ≥148 pmol/L, vitamin B-12-deficient children had a 1.89-times higher adjusted rate (95% CI: 1.53, 2.34; P < 0.0001). Anemia was related to a 72% higher rate (95% CI: 48%, 99%; P < 0.0001), whereas every 5-fL difference in MCV was associated with a 7% lower adjusted rate (95% CI: 4%, 10%; P < 0.0001). Vitamin B-12 deficiency was associated with risk of grade repetition and school absenteeism rates in school children from Bogota, Colombia. The effects of correcting vitamin B-12 deficiency on educational outcomes and neurocognitive development of school children need to be determined in intervention studies. © 2015 American Society for

The Emerging Role of Vitamin B6 in Inflammation and Carcinogenesis.

PubMed

Bird, Ranjana P

Vitamin B6 serves as a coenzyme catalyzing more than 150 enzymes regulating metabolism and synthesis of proteins, carbohydrates, lipids, heme, and important bioactive metabolites. For several years vitamin B6 and its vitamers (B6) were recognized as antioxidant and antiinflammatory and in modulating immunity and gene expression. During the last 10 years, there were growing reports implicating B6 in inflammation and inflammation-related chronic illnesses including cancer. It is unclear if the deficiency of B6 or additional intake of B6, above the current requirement, should be the focus. Whether the current recommended daily intake for B6 is adequate should be revisited, since B6 is important to human health beyond its role as a coenzyme and its status is affected by many factors including but not limited to age, obesity, and inflammation associated with chronic illnesses. A link between inflammation B6 status and carcinogenesis is not yet completely understood. B6-mediated synthesis of H 2 S, a gasotransmitter, and taurine in health and disease, especially in maintaining mitochondrial integrity and biogenesis and inflammation, remains an important area to be explored. Recent developments in the molecular role of B6 and its direct interaction with inflammasomes, and nuclear receptor corepressor and coactivator, receptor-interacting protein 140, provide a strong impetus to further explore the multifaceted role of B6 in carcinogenesis and human health. © 2018 Elsevier Inc. All rights reserved.

Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer

PubMed Central

Vashi, Pankaj; Edwin, Persis; Popiel, Brenten; Lammersfeld, Carolyn; Gupta, Digant

2016-01-01

Background/Aims Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer. Methods This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard". Results Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in

Neurologic Manifestations of Vitamin B Deficiency after Bariatric Surgery.

PubMed

Punchai, Suriya; Hanipah, Zubaidah Nor; Meister, Katherine M; Schauer, Philip R; Brethauer, Stacy A; Aminian, Ali

2017-08-01

The aim of this study was to assess the incidence, clinical presentation, and outcomes of neurologic disorders secondary to vitamin B deficiencies following bariatric surgery. Patients at a single academic institution who underwent bariatric surgery and developed neurologic complications secondary to low levels of vitamins B1, B2, B6, and B12 between the years 2004 and 2015 were studied. In total, 47 (0.7%) bariatric surgical patients (Roux-en-Y gastric bypass n = 36, sleeve gastrectomy n = 9, and duodenal switch n = 2) developed neurologic manifestations secondary to vitamin B deficiencies. Eleven (23%) patients developed postoperative anatomical complications contributed to poor oral intake. Median duration to onset of neurologic manifestation following surgery was 12 months (IQR, 5-32). Vitamin deficiencies reported in the cohort included B1 (n = 30), B2 (n = 1), B6 (n = 12), and B12 (n = 12) deficiency. The most common manifestations were paresthesia (n = 31), muscle weakness (n = 15), abnormal gait (n = 11), and polyneuropathy (n = 7). Four patients were diagnosed with Wernicke-Korsakoff syndrome (WKS) which was developed after gastric bypass (n = 3) and sleeve gastrectomy (n = 1). Seven patients required readmission for management of severe vitamin B deficiencies. Overall, resolution of neurologic symptoms with nutritional interventions and pharmacotherapy was noted in 40 patients (85%). The WKS was not reversible, and all four patients had residual mild ataxia and nystagmus at the last follow-up time. Nutritional neurologic disorders secondary to vitamin B deficiency are relatively uncommon after bariatric surgery. While neurologic disorders are reversible in most patients (85%) with vitamin replacements, persistent residual neurologic symptoms are common in patients with WKS.

Molecular identification of Gd A- and Gd B- G6PD deficient variants by ARMS-PCR in a Tunisian population.

PubMed

Haloui, Sabrine; Laouini, Naouel; Sahli, Chaima Abdelhafidh; Daboubi, Rim; Becher, Mariem; Jouini, Latifa; Kazdaghli, Kalthoum; Tinsa, Faten; Cherif, Semia; Khemiri, Monia; Fredj, Sondess Hadj; Othmani, Rim; Ouali, Faida; Siala, Hajer; Toumi, Nour El Houda; Barsaoui, Sihem; Bibi, Amina; Messaoud, Taieb

2016-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy. More than 200 mutations in the G6PD gene have been described. In Tunisia, the A-African and the B-Mediterranean mutations predominate the mutational spectrum. The purpose of this study was to apply the amplification refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and Gd B- variants in a cohort of deficient individuals and to establish a phenotype/genotype association. 90 subjects were screened for enzymatic deficiency by spectrophotometric assay. The molecular analyses were performed in a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no mutations have been identified. The ARMS-PCR showed complete concordance with the endonuclease cleavage reference method and agreed perfectly with previous Tunisian studies where Gd A- and Gd B- were the most encountered. Also, similarities in spectrum mutations with North African and Mediterranean countries suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS has been introduced in this study for common G6PD alleles identification in Tunisia. It gives some advantages compared to the traditional endonuclease digestion method since it is more convenient and timesaving and also offers the possibility to be applied in mass screening surveys.

Prevalence of G6PD deficiency and associated haematological parameters in children from Botswana.

PubMed

Motshoge, Thato; Ababio, Grace; Aleksenko, Larysa; Souda, Sajini; Muthoga, Charles Waithaka; Mutukwa, Naledi; Tawe, Leabaneng; Ramatlho, Pleasure; Gabaitiri, Lesego; Chihanga, Simon; Mosweunyane, Tjantilili; Hamda, Shimeles; Moakofhi, Kentse; Ntebela, Davies; Peloewetse, Elias; Mazhani, Loeto; Pernica, Jeffrey M; Read, John; Quaye, Isaac K; Paganotti, Giacomo Maria

2018-05-17

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is commonly seen in malaria endemic areas as it is known to confer a selective advantage against malaria. Recently, we reported a high proportion of asymptomatic reservoir of Plasmodium vivax in Botswana, that calls for intervention with primaquine to achieve radical cure of vivax malaria. Considering that individuals with this enzyme deficiency are at risk of haemolysis following primaquine treatment, assessment of the population for the relative frequency of G6PD deficiency is imperative. Samples from 3019 children from all the districts of Botswana were successfully genotyped for polymorphisms at positions 202 and 376 of the G6PD gene. Haematological parameters were also measured. The overall population allele frequency (based on the hemizygous male frequency) was 2.30% (95% CI, 1.77-2.83), while the overall frequency of G6PD-deficient genotypes A- (hemizygote and homozygote genotypes only) was 1.26% (95% CI, 0.86-1.66). G6PD deficiency is spread in Botswana according to the historical prevalence of malaria with a North-West to South-East decreasing gradient trend. There was no association between G6PD status and P. vivax positivity. G6PD A- form was found to be associated with decreased RBC count and haemoglobin levels without a known cause or illness. In conclusion, we report for the first time the prevalence of G6PD deficiency in Botswana which is relevant for strategies in the malaria elimination campaign. Further work to examine the activities of the enzyme in the Botswana population at risk for malaria is warranted. Copyright © 2017. Published by Elsevier B.V.

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Isa, Hasan M; Mohamed, Masooma S; Mohamed, Afaf M; Abdulla, Adel; Abdulla, Fuad

2017-04-01

This study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus. This is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients. Of 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male ( P <0.0001), and had lower Hb levels ( P <0.0001) and higher maximum bilirubin levels ( P =0.001). More G6PD-deficient patients needed ET ( P <0.0001). G6PD deficiency ( P =0.006), lower Hb level ( P =0.002), lower hematocrit count ( P =0.02), higher bilirubin level ( P <0.0001), higher maximal bilirubin level ( P <0.0001), and positive blood culture result ( P <0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus ( P =0.021) and independently related to ET ( P =0.03). G6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice

PubMed Central

Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

2016-01-01

Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects. PMID:26835453

Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

2016-01-01

Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects.

Increased risk of iron deficiency and reduced iron absorption but no difference in zinc, vitamin A or B-vitamin status in obese women in India.

PubMed

Herter-Aeberli, Isabelle; Thankachan, Prashanth; Bose, Beena; Kurpad, Anura V

2016-12-01

Two objectives were investigated: (1) to assess the risk of micronutrient deficiencies in relation to weight status in Indian women with a focus on iron but also including zinc, vitamin A and B vitamins and (2) to compare fractional iron absorption between obese (OB) and normal weight (NW) women. Part 1 was a cross-sectional study including 146 healthy, middle-class women from Bangalore, India, with a BMI between 19 and 40 kg/m 2 . Anthropometrics and blood pressure were measured, and a fasting blood sample was obtained for the analysis of vitamin and mineral status, hepcidin, blood lipids and glucose. In part 2, 16 OB and 13 NW women consumed a standardized test meal labeled with the stable iron isotope 57 Fe. Incorporation of the iron isotope into erythrocytes was measured 14 days later. In addition, iron status, hepcidin and inflammatory markers were determined. In part 1, compared to NW women, overweight/OB subjects had significantly higher C-reactive protein, serum ferritin, soluble transferrin receptor (sTfR) and hepcidin concentrations (p < 0.05). The odds ratio for having high sTfR concentrations (i.e., low iron status) with increasing BMI was 1.09 (95 % CI 1.02-1.17). None of the other micronutrients investigated showed any differences between weight status groups. In part 2, fractional iron absorption was significantly lower in the OB group compared to the NW group even after controlling for differences in iron status (10.0 ± 6.5 vs. 16.7 ± 4.6 %; p = 0.038). OB women in Bangalore have an increased risk of low iron status and absorb less dietary iron; however, their risk of other micronutrient deficiencies was similar to NW women. Our results clearly demonstrate the importance of considering the double burden of malnutrition in the planning of prevention strategies especially in transition countries with emerging obesity epidemics.

Pyridoxal-5'-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients.

PubMed

Molina-López, Jorge; Florea, Daniela; Quintero-Osso, Bartolomé; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Del Pozo, Elena Planells

2016-06-01

Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of pyridoxal-5'-phosphate decreasing their body reserves. This study was designed to assess the nutritional pyridoxal-5'-phosphate status in critical care patients with systemic inflammatory response syndrome, comparing them with a group of healthy people, and studying it's association with factors involved in the pyridoxine and other B vitamins metabolism, as the total antioxidant capacity and Hcy as cardiovascular risk biomarker. Prospective, multicentre, comparative, observational and analytic study. One hundred and three critically ill patients from different hospitals, and eighty four healthy subjects from Granada, Spain, all with informed consent. Data from daily nutritional assessment, ICU severity scores, clinical and nutritional parameters, antioxidant status and homocysteine levels was taken at admission and at the seventh day of the ICU stay. Thiamine, riboflavin, pyridoxine and folate status proved deficient in a large number of patients, being significantly lower in comparison with control group, and significantly decreased at 7th day of ICU stay. Higher homocysteine was observed in patients compared with control group (p < 0.05) where 31.5 and 26.8 percent of subjects presented hyperhomocysteinemia at initial and final of study, respectively. Antioxidant status was lower than control group in two periods analysed, and decreased at 7th day of ICU stay (p < 0.05) being associated with PLP deficiency. PLP deficiency was also correlated with hyperhomocysteinemia at two times measured (r. -0.73, p < 0.001; r. -0.69, p < 0.001, respectively), showing at day 7 an odds ratio of 6.62 in our multivariate model. Critically ill patients with SIRS show deficient B vitamin and low antioxidant statuses. Despite association found between PLP deficiency and low antioxidant status in critically ill patients, PLP deficiency

Glucose-6-phosphate dehydrogenase deficiency (G6PD) as a risk factor of male neonatal sepsis.

PubMed

Rostami-Far, Z; Ghadiri, K; Rostami-Far, M; Shaveisi-Zadeh, F; Amiri, A; Rahimian Zarif, B

2016-01-01

Introduction. Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods. This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results. The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions. G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.

FAD-induced in vitro activation of glutathione reductase in the lens of B2 deficient rats.

PubMed

Ono, S; Hirano, H

1984-04-01

We studied the FAD-induced in vitro stimulation of lenticular glutathione reductase in riboflavin-deficient rats. The stimulatory effect of FAD on lenticular glutathione reductase in rats fed a B2-deficient diet for 4 weeks was remarkably higher than in paired control rats fed a B2-supplemented basal diet and control rats had ad libitum access to a B2-supplemented basal diet. The in vitro FAD stimulation effect on rat lenticular glutathione reductase represents a sensitive indicator of the B2 deficient status.

High prevalence of suboptimal vitamin B12 status in young adult women of South Asian and European ethnicity.

PubMed

Quay, Teo A W; Schroder, Theresa H; Jeruszka-Bielak, Marta; Li, Wangyang; Devlin, Angela M; Barr, Susan I; Lamers, Yvonne

2015-12-01

Suboptimal vitamin B12 (B12) status has been associated with an increased risk of congenital anomalies, preterm birth, and childhood insulin resistance. South Asians - Canada's largest minority group - and women of reproductive age are vulnerable to B12 deficiency. This study aimed to assess the prevalence of and factors associated with B12 deficiency and suboptimal B12 status in a convenience sample of young adult women of South Asian and European descent in Metro Vancouver. We measured serum B12, holotranscobalamin, plasma methylmalonic acid, red blood cell and plasma folate, and hematologic parameters in 206 nonpregnant, healthy women aged 19-35 years. Categorization for B12 status adhered to serum B12 cutoffs for deficiency (<148 pmol/L) and suboptimal B12 status (148-220 pmol/L). We collected demographic, lifestyle, and dietary intake data and conducted genotyping for common genetic variants linked to B-vitamin metabolism. The prevalence of deficiency and suboptimal B12 status were 14% and 20%, respectively. Serum vitamin B12 concentrations were negatively associated with oral contraceptive use and first-generation immigrant status, and positively with dietary B12 intake and B12 supplement use. The prevalence of B12 inadequacy in this sample of highly educated women is higher than in the general Canadian population. In light of maternal and fetal health risks associated with B12 inadequacy in early-pregnancy, practitioners should consider monitoring B12 status before and during early pregnancy, especially in immigrants and women with low dietary B12 intakes including non-users of vitamin supplements.

Evaluation of Vitamin B12 Deficiency and Associated Factors in Patients With Systemic Sclerosis.

PubMed

Tas Kilic, Diler; Akdogan, Ali; Kilic, Levent; Sari, Alper; Erden, Abdulsamet; Armagan, Berkan; Kilickaya, Muhammed; Kalyoncu, Umut; Turhan, Turan; Kiraz, Sedat; Karaahmetoglu, Selma

2018-01-30

In patients with systemic sclerosis (SSc) gastrointestinal (GI) involvement, nutritional status and medications may lead to cobalamin (Vit B12) deficiency. We aimed to determine the frequency and the potential causes of Vit B12 deficiency in SSc patients. We conducted a cross-sectional analysis of 62 SSc patients in a single center in 1 year period. Medical history and physical examination of patients were reevaluated. Data about organ involvements were obtained from hospital file records. The nutritional status of the patients was assessed with Malnutrition Universal Screening Tool (MUST). Vit B12, homocysteine (except in three patients) and Helicobacter Pylori Immunoglobulin G (H. Pylori IgG) levels were measured in all patients. Vit B12 deficiency was considered as serum Vit B12 level <200 pg/mL or being on Vit B12 replacement therapy. Serum Vit B12 levels of the patients were also grouped as low (<200 pg/mL), borderline (200-300 pg/mL) and normal (>300 pg/mL). Plasma homocysteine levels of the patients were classified as elevated (>9 μmol/L) and hyperhomocysteinemia (>15 μmol/L). Mann-Whitney U and Kruskal-Wallis tests were used to compare parameters among the groups. Correlation was tested by Spearman's correlation coefficient. Forty-four (71.0%) patients were defined as Vit B12 deficient; 22 had Vit B12 level <200 pg/mL (four were on Vit B12 replacement therapy) and the remaining 22 had Vit B12 >200 pg/mL and were already on Vit B12 replacement therapy. The percentage of the patients with hyperhomocysteinemia was significantly higher in the group with Vit B12 <200 pg/mL as compared to other groups (P = 0.004) but only 33.3% (7/21) of the patients with Vit B12 <200 pg/mL had hyperhomocysteinemia. There were no statistically significant differences between patients with and without Vit B12 deficiency regarding age, mean disease duration, MUST scores, mean hemoglobin levels, H. Pylori IgG positivity and organ involvements (P > 0.05 for all). Vit B12 deficiency

Glucose-6-phosphate dehydrogenase deficiency

MedlinePlus

G6PD deficiency; Hemolytic anemia due to G6PD deficiency; Anemia - hemolytic due to G6PD deficiency ... Gallagher PG. Hemolytic anemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 161. Janz ...

Changes in barrier health status of the gill for grass carp (Ctenopharyngodon idella) during valine deficiency: Regulation of tight junction protein transcript, antioxidant status and apoptosis-related gene expression.

PubMed

Feng, Lin; Luo, Jian-Bo; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

2015-08-01

This study investigated the effects of dietary valine on tight junction protein transcription, antioxidant status and apoptosis on grass carp gills (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of valine (4.3, 8.0, 10.6, 13.1, 16.7, 19.1 g/kg). The results indicated that valine deficiency decreased Claudin b, Claudin 3, Occludin and ZO-1 transcription and increased Claudin 15 expression in the fish gill (P < 0.05). These effects were partly due to the down-regulation of interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and IκB α and the up-regulation of relative mRNA expression of interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and nuclear factor κB P65 (NF-κB P65) (P < 0.05). However, valine deficiency and valine supplementation did not have a significant effect on Claudin c and Claudin 12 expression in grass carp gills (P > 0.05). Valine deficiency also disrupted antioxidant status in the gill by decreasing anti-superoxide radicals and hydroxyl radical capacity, glutathione contents and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) (P < 0.05). These results may be ascribed to the down-regulation of NF-E2-related factor 2 (Nrf2), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1) and the up-regulation of Kelch-like-ECH-associated protein 1 (Keap1) (P < 0.05). Additionally, valine deficiency induced DNA fragmentation via the up-regulation of Caspase 3, Caspase 8 and Caspase 9 expressions (P < 0.05). These results may be ascribed to the improvement in ROS levels in the fish gill (P < 0.05). Taken together, the results showed that valine deficiency impaired the structural integrity of fish gill by disrupted fish antioxidant defenses and regulating the expression of tight junction protein, cytokines, antioxidant

Vitamin B6 status, immune response and inflammation markers in kidney transplant recipients treated with polyclonal anti-thymocyte globulin.

PubMed

Jankowska, M; Trzonkowski, P; Dębska-Ślizień, A; Marszałł, M; Rutkowski, B

2014-10-01

Vitamin B6 status has an impact on the body's inflammatory and immune responses. Immunosuppressive therapy may influence vitamin B6 metabolism in kidney transplant recipients. Treatment with polyclonal anti-thymocyte globulin (ATG) is associated with long-term changes in inflammatory and immune parameters. It is not known if ATG therapy also may have an impact on vitamin B6 status in kidney transplant recipients. We aimed to analyze the impact of therapy with ATG on vitamin B6 status, immune response, and the profile of inflammatory cytokines. This was a retrospective, observational study that included 44 kidney allograft recipients. Twenty patients received induction therapy with ATG (6 to 24 months before enrollment). Twenty-four patients constituted the control group, matched with respect to time since transplantation. The B6 vitamers, total lymphocyte count, CD3 percentage, interleukin (IL)-6, -7, and -10, transforming growth factor β, interferon γ, and chemokine ligand 21 were analyzed in a study group. All indicators of vitamin B6 status were lower in the ATG group than in the control group. There were also significant differences with respect to immune response (significantly lower total lymphocyte count and CD3 in the ATG group) and inflammatory status (significantly higher IL-6 and IL-10 in the ATG group). Vitamin B6 vitamers and derivatives were not related to lymphocyte count and cytokine levels or to estimated glomerular filtration rate and age of the study population. Vitamin B6 stores and active forms are lower in kidney transplant recipients treated with ATG. ATG therapy promotes CD3 and total lymphocyte depletion and increases indicators of inflammation. We found no associations between vitamers of B6, immune response cells, and inflammatory cytokines in study population.

Comparative Study of Antimalarial and Other Drugs on G6PD Deficient Red Cells.

DTIC Science & Technology

33063 (1600 mg x day for 6 days) and WR 30090 (690 mg x day for 3- 6 days) demonstrated that these drugs were not hemolytic for G6PD deficient red cells...The studies concerning the effects of DFD on G6PD deficient red cells of the A- and B- variants were completed during the course of this contract...DFD is especially hemolytic even at low single dosages for G6PD deficient red cells of the B- type. The investigations on the new antimalarials WR

Vitamin B6 is essential for serine de novo biosynthesis.

PubMed

Ramos, Rúben J; Pras-Raves, Mia L; Gerrits, Johan; van der Ham, Maria; Willemsen, Marcel; Prinsen, Hubertus; Burgering, Boudewijn; Jans, Judith J; Verhoeven-Duif, Nanda M

2017-11-01

Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.

Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficiency in women.

PubMed

Peters, Anna L; Van Noorden, Cornelis J F

2009-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a X-chromosomally transmitted disorder of the erythrocyte that affects 400 million people worldwide. Diagnosis of heterozygously-deficient women is complicated: as a result of lyonization, these women have a normal and a G6PD-deficient population of erythrocytes. The cytochemical assay is the only reliable assay to discriminate between heterozygously-deficient women and non-deficient women or homozygously-deficient women. G6PD deficiency is mainly found in areas where malaria is or has been endemic. In these areas, malaria is treated with drugs that can cause (severe) hemolysis in G6PD-deficient individuals. A cheap and reliable test is necessary for diagnosing the deficiency to prevent hemolytic disorders when treating malaria. In this review, it is concluded that the use of two different tests for diagnosing men and women is the ideal approach to detect G6PD deficiency. The fluorescent spot test is inexpensive and easy to perform but only reliable for discriminating hemizygous G6PD-deficient men from non-deficient men. For women, the cytochemical assay is recommended. However, this assay is more expensive and difficult to perform and should be simplified into a kit for use in developing countries.

Anemia in patients with coinherited thalassemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Pornprasert, Sakorn; Phanthong, Siratcha

2013-01-01

Thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are genetic disorders that cause hemolytic anemia. In areas with high frequencies of both hematological disorders, coinheritance of G-6-PD deficiency with thalassemia can be found. Whether G-6-PD deficiency, coinherited with thalassemia, enhances severe anemia is still unclear. Hematological parameters between thalassemia carriers with G-6-PD deficiency and those without G-6-PD deficiency were compared. The G-6-PD deficiency was diagnosed in 410 blood samples from thalassemia patients using a fluorescent spot test. The levels of hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and Hb A2/Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] were measured using an automated blood counter and high performance liquid chromatography (HPLC), respectively. The G-6-PD deficiency was found in 37 samples (9.02%). Mean levels of Hb, PCV, MCV and Hb A2/E were similar between the two groups. Thus, G-6-PD deficiency did not enhance red blood cell pathology or induce more anemic severity in thalassemia patients.

Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

PubMed Central

Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

2015-01-01

Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

Glucose-6-phosphate dehydrogenase deficiency.

PubMed

Cappellini, M D; Fiorelli, G

2008-01-05

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community.

Neurological consequences of vitamin B12 deficiency and its treatment.

PubMed

Chalouhi, Christel; Faesch, Sabine; Anthoine-Milhomme, Marie-Constance; Fulla, Yvonne; Dulac, Olivier; Chéron, Gérard

2008-08-01

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.

Parental discussion of G6PD deficiency and child health: implications for clinical practice.

PubMed

Guan, Yue; Roter, Debra L; Huang, Aichu; Erby, Lori A H; Chien, Yin-Hsiu; Hwu, Wuh-Liang

2014-03-01

Parents are encouraged to discuss self-care with children affected by G6PD deficiency; however, little is known about the extent or impact of these discussions on the physical and psychosocial health of these children. The purpose of this study was to examine the nature of parental-child discussions of G6PD deficiency self-care and their relationship to child health. A quantitative cross-sectional survey of 178 Taiwanese parents of children with G6PD deficiency was conducted. The extent of parental-child self-care discussions was assessed in regards to coverage of nine key topics. Parent's G6PD deficiency status, knowledge of haemolytic anaemia symptoms and reported G6PD deficiency education from providers were examined as correlates of parental discussion. Child health was assessed with the child health questionnaire-parent form (Chinese version) and a 13-item haemolytic anaemia symptom list. Self-care discussions were positively correlated with parental G6PD deficiency status (β=2.08, p=0.03), accurate identification of haemolytic anaemia symptoms (β=0.18, p=0.01), the thoroughness and clarity of patient education (β=0.14, p<0.001) and child age (β=1.04, p<0.001). Among children reported to have experienced significant symptoms of acute haemolytic anaemia (35%), the extent of self-care discussions was positively associated with reported physical and psychosocial child health (β=1.18, p<0.001). Parental-child G6PD deficiency self-care discussions are associated with better child health, and parental involvement in these discussions is facilitated by the thoroughness and clarity of patient education received from providers.

G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients

PubMed Central

Dore, Maria Pina; Marras, Giuseppina; Rocchi, Chiara; Soro, Sara

2016-01-01

Background Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. Methods We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. Results Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. Conclusions These results demonstrate for the first time that G6PD deficiency does not enhance patients’ susceptibility to acquire H. pylori infection in Sardinia. PMID:27467818

[Vitamin B12 Deficiency in Type 2 Diabetes Mellitus].

PubMed

Tavares Bello, Carlos; Capitão, Ricardo Miguel; Sequeira Duarte, João; Azinheira, Jorge; Vasconcelos, Carlos

2017-10-31

Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values < 0.05. The study included a total of 1007 patients (58% women) with a mean age of 66.4 ± 12.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (< 174 ng / dL) was present in 21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p < 0.001), and calcium channel blockers (26.8% vs 18.2%; p = 0.001). After adjustment for possible

Intake of medication and vitamin status in the elderly.

PubMed

Fabian, Elisabeth; Bogner, Michaela; Kickinger, Andrea; Wagner, Karl-Heinz; Elmadfa, Ibrahim

2011-01-01

An inadequate vitamin status is associated with higher morbidity and frailty in the elderly and might be due to medication. This study aimed to evaluate the status of several vitamins in relation to regular intake of medication in this population. A total of 102 non-institutionalized subjects aged 70-90 years were recruited. Plasma levels of vitamins A, D, E, K and C were determined by HPLC. The functional parameters of vitamins B(1), B(2) and B(6), i.e. the activities of the erythrocyte enzymes transketolase, glutathione reductase and glutamic oxaloacetic transaminase were analyzed photometrically; plasma folate and vitamin B(12) were determined by RIA. The status of vitamins A, E and C was generally satisfactory. Eighty-eight percent and 42% of participants were deficient in vitamins D and K, respectively, as were 29% in B(6); up to 10% were deficient in vitamins B(1), B(2), B(12) and folate. A considerable percentage of participants was, however, at risk for vitamin deficiencies (vitamins B(1), B(6), B(12) and folate: 20-30%; vitamin B(2): 60%). Regular intake of maximally 2 drugs per day was not adversely related to the status of several vitamins; intake of ≥ 3 drugs per day was significantly negatively associated with the status of vitamins D, K, B(6) and folate. Daily intake of ≥ 3 drugs was found to be adversely associated with the status of some vitamins in the elderly. Hence, the medication schedule and nutritional status of these subjects should be monitored closely to ensure that the daily micronutrient requirement is fulfilled. Copyright © 2011 S. Karger AG, Basel.

Vegan Diet, Subnormal Vitamin B-12 Status and Cardiovascular Health

PubMed Central

Woo, Kam S.; Kwok, Timothy C.Y.; Celermajer, David S.

2014-01-01

Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases. PMID:25195560

Vegan diet, subnormal vitamin B-12 status and cardiovascular health.

PubMed

Woo, Kam S; Kwok, Timothy C Y; Celermajer, David S

2014-08-19

Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases.

Vitamin B12 deficiency

USDA-ARS?s Scientific Manuscript database

Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, sub...

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.

PubMed

Del Bo', Cristian; Riso, Patrizia; Gardana, Claudio; Brusamolino, Antonella; Battezzati, Alberto; Ciappellano, Salvatore

2018-02-15

Vegetarians and vegans are more vulnerable to vitamin B 12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 μg. However, single large oral doses of vitamin B 12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B 12 (350 μg/week vs 2000 μg/week) in improving cyanocobalamin (vitamin B 12 ) nutritional status in vegans and vegetarians with a marginal deficiency. A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B 12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 μg/week) and control group Hd (high dose, 2000 μg/week) vitamin B 12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B 12 , related metabolic markers, and blood cell counts. Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B 12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (LdvsHd). No effect was detected for vitamin B 6 and blood cell count. In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B 12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 μg/day (350�

Education and micronutrient deficiencies: an ecological study exploring interactions between women's schooling and children's micronutrient status.

PubMed

Harding, Kassandra L; Aguayo, Victor M; Masters, William A; Webb, Patrick

2018-04-10

Formal education can be a nutrition-sensitive intervention that supports the scale-up and impact of nutrition-specific actions. Maternal education has long been linked to child survival, growth, and development while adult earnings and nutrition are tied to years in school as a child. However, less is known about the relationship between maternal education and the micronutrient status of children, women and the general population. Using country-level data and an ecological study design, we explored the global associations between women's educational attainment and: a) anemia and vitamin A deficiency (VAD) in children aged 6-59 months; b) anemia in non-pregnant women; and c) zinc deficiency, urinary iodine excretion (UIE), and the proportion of infants protected against iodine deficiency in the general population Cross-sectional relationships (2005-2013) were assessed using linear regression models. Percentage of women without schooling was negatively associated with all outcomes. Number of years of schooling among women was positively associated with all outcomes except for UIE and the proportion of infants protected against iodine deficiency. Income level was a significant effect modifier of the effect of years of women's schooling on child anemia as well as of the proportion of women without formal education on zinc deficiency in the population. The relationship was strongest in low-income countries for child anemia, and was not significant in upper middle-income countries. For zinc deficiency, the relationship was not significant in low or lower middle income countries, which may suggest that a minimum threshold of resources needs to be reached before education can influence zinc status. While relationships between maternal schooling and micronutrient outcomes vary around the globe, more schooling is generally linked to lower rates of deficiency. These findings draw policy-relevant connections between formal education and anemia and micronutrient status

Folate and vitamin B12 status of adolescent girls in northern Nigeria.

PubMed Central

VanderJagt, D. J.; Spelman, K.; Ambe, J.; Datta, P.; Blackwell, W.; Crossey, M.; Glew, R. H.

2000-01-01

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12. PMID:10946529

Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial.

PubMed

Winkels, Renate M; Brouwer, Ingeborg A; Clarke, Robert; Katan, Martijn B; Verhoef, Petra

2008-08-01

Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). The consumption of fortified bread increased serum folate concentrations by 45% (mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49% (mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to 0% after 12 wk. Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.

Intravenous Vitamin B6 Increases Resistance to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: A Randomized Controlled Trial.

PubMed

Obi, Yoshitsugu; Mikami, Satoshi; Hamano, Takayuki; Obi, Yasue; Tanaka, Hirotaka; Shimomura, Akihiro; Rakugi, Hiromi; Inoue, Toru; Isaka, Yoshitaka

2016-11-01

Vitamin B6 deficiency is common in hemodialysis patients and may contribute to anemia and abnormal bone metabolism in this population. 6-month, open-label, randomized controlled parallel-group study in hemodialysis centers. Fifty-six maintenance hemodialysis patients with relatively high resistance to erythropoiesis-stimulating agents (ESA). Intravenous vitamin B6 (60 mg of intravenous pyridoxal 5'-phosphate after each thrice-weekly hemodialysis session). The primary and secondary outcomes were changes over time in ESA resistance index and bone turnover markers, respectively. The prevalence of vitamin B6 deficiency was 40% overall. Compared with the control group, the B6 group showed an upward change in ESA resistance index over time (P interaction  = .038). At week 13 (a priori-defined time point), pyridoxal 5'-phosphate administration was associated with higher ESA resistance index by 0.97 (95% confidence interval, 0.02-1.92) ×10 -2  μg ⋅darbepoetin-α/kg per g/dL⋅hemoglobin after baseline adjustment, which was not modified by baseline vitamin B6 status. There was a trend toward increase in serum erythropoietin concentrations in the B6 group after adjustment for baseline values, hemoglobin, and weekly ESA dose (P interaction  = .06). The downward changes of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b in the B6 group relative to the control group were pronounced in patients without vitamin B6 deficiency (P interaction < .001 and .017, respectively), despite nonsignificant between-group difference in 1-84 parathyroid hormone. Thrice-weekly intravenous vitamin B6 (60 mg pyridoxal 5'-phosphate hydrate) worsens the response to ESA and may blunt the response of bone to parathyroid hormone in hemodialysis patients. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies.

PubMed

Mathis, Déborah; Abela, Lucia; Albersen, Monique; Bürer, Céline; Crowther, Lisa; Beese, Karin; Hartmann, Hans; Bok, Levinus A; Struys, Eduard; Papuc, Sorina M; Rauch, Anita; Hersberger, Martin; Verhoeven-Duif, Nanda M; Plecko, Barbara

2016-09-01

Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for further molecular work-up. This has so far been investigated in only a small number of patients. We evaluated the vitamin B6 vitamers pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the catabolite pyridoxic acid (PA) in the so far largest patient cohort: reference (n = 50); pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency (n = 6); antiquitin (ATQ) deficiency (n = 21); tissue non-specific alkaline phosphatase (TNSALP) deficiency (n = 2) and epileptic encephalopathy (EE) of unknown etiology tested negative for ATQ and PNPO deficiency (n = 64). High plasma PM concentration was found in all patients with PNPO deficiency irrespective of vitamin B6 supplementation. Their PM concentration and the PM/PA ratio was significantly higher (p < 0.0001), compared to any other patients analysed. One patient with TNSALP deficiency and sampling prior to PN supplementation had markedly elevated plasma PLP concentration. On PN supplementation, patients with TNSALP deficiency, ATQ deficiency and patients of the EE cohort had similar plasma vitamin B6 profiles that merely reflect the intake of supra-physiological doses of vitamin B6. The interval of sampling to the last PN intake strongly affected the plasma concentrations of PN, PL and PA. PM concentrations and the PM/PA ratio clearly separated PNPO-deficient patients from the other cohorts. The plasma PM/PA ratio thus represents a robust biomarker for the selective screening of PNPO deficiency.

Pediatric Provider Insight Into Newborn Screening for Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Bernardo, Janine; Nock, Mary

2015-06-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a major contributor to neonatal hyperbilirubinemia, yet newborn screening for this disorder in the United States is not standard practice. We surveyed pediatric providers regarding a novel newborn G6PD screening program successfully implemented in 2007 at a US urban women's hospital newborn nursery. An electronic survey was distributed to 472 pediatric providers addressing extent to which they were influenced by the screening program. Ninety-two (20%) providers responded, of whom 74 (80%) had taken care of G6PD-deficient patients diagnosed by the screening program. A majority found the diagnosis helpful for patient management and influential in their management. Most common changes in management included more counseling on jaundice and follow-up and avoidance of hemolytic crisis triggers. General pediatric providers support newborn G6PD screening and appreciate the current program. Knowing the G6PD deficiency status of newborns informed and influenced pediatric providers' care. © The Author(s) 2014.

VITAMIN B-12 SUPPLEMENTATION OF DEFICIENT LACTATING GUATEMALAN WOMEN IMPROVES MATERNAL BUT NOT INFANT STATUS

USDA-ARS?s Scientific Manuscript database

Vitamin B-12 deficiency is common in mothers and infants where maternal intake of animals source foods is low. The first six months post-partum is a critical period of neurological development requiring vitamin B-12. A pilot study was designed to determine the dose of B-12 to the mothers that would ...

Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yang-Che; Wu, Yu-Hsueh; Tseng, Chih-Huang; Sun, Andy

2016-10-01

Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA + /DG + /EOLP patients). The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA + /DG + /EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups. We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA + /DG + /EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL), iron (< 60 μg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA + /DG + /EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA + /DG + /EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p < 0.001). Of 27 anemic GPCA + /DG + /EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA + /DG + /EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia. We conclude that GPCA + /DG + /EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA + /DG + /EOLP patients may sometimes have normocytic anemia or iron deficiency anemia. Copyright © 2016. Published by Elsevier B.V.

Vitamin B12 deficiency: unusual cause of jaundice in an adolescent.

PubMed

Katakam, Phalguna Kousika; Hegde, Asha P; Venkataramaiahyappa, Manju

2018-01-12

Vitamin B 12 deficiency in vegans is a known cause of megaloblastic anaemia. We report an adolescent girl who presented with jaundice and weight loss for 6 months secondary to vitamin B 12 deficiency, leading to megaloblastic anaemia. Replacement with vitamin B 12 reversed her symptoms, resulting in weight gain, and normalised her haemoglobin, red blood cell morphology, bilirubin levels and serum vitamin B 12 levels. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Luzzatto, Lucio; Nannelli, Caterina; Notaro, Rosario

2016-04-01

G6PD is a housekeeping gene expressed in all cells. Glucose-6-phosphate dehydrogenase (G6PD) is part of the pentose phosphate pathway, and its main physiologic role is to provide NADPH. G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age. G6PD-deficient persons are mostly asymptomatic, but they can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or when they are exposed to certain infections or drugs. G6PD deficiency is a global health issue. Copyright © 2016 Elsevier Inc. All rights reserved.

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.

PubMed

Ahmed, Marwan A; Muntingh, George; Rheeder, Paul

2016-10-07

The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3

Micronutrient Deficiencies Are Common in 6- to 8-Year-Old Children of Rural Nepal, with Prevalence Estimates Modestly Affected by Inflammation12

PubMed Central

Schulze, Kerry J.; Christian, Parul; Wu, Lee S.-F.; Arguello, Margia; Cui, Hongjie; Nanayakkara-Bind, Ashika; Stewart, Christine P.; Khatry, Subarna K.; LeClerq, Steven; West, Keith P.

2014-01-01

Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for which comprehensive data are lacking in school-aged children. We assessed the micronutrient status of Nepalese children, aged 6 to 8 y, born to mothers who participated in a community-based antenatal micronutrient supplementation trial from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a random sample of 1000 children. Results revealed deficiencies of vitamins A (retinol <0.70 μmol/L, 8.5%), D (25-hydroxyvitamin D <50 nmol/L, 17.2%), E (α-tocopherol <9.3 μmol/L, 17.9%), K (decarboxy prothombin >2 μg/L, 20%), B-12 (cobalamin <150 pmol/L, 18.1%), B-6 [pyridoxal-5′-phosphate (PLP) <20 nmol/L, 43.1%], and β-carotene (41.5% <0.09 μmol/L), with little folate deficiency (6.2% <13.6 nmol/L). Deficiencies of iron [ferritin <15 μg/L, 10.7%; transferrin receptor (TfR) >8.3 mg/L, 40.1%; TfR:ferritin >500 μg/μg, 14.3%], iodine (thyroglobulin >40 μg/L, 11.4%), and selenium (plasma selenium <0.89 μmol/L, 59.0%) were observed, whereas copper deficiency was nearly absent (plasma copper <11.8 μmol/L, 0.7%). Hemoglobin was not assessed. Among all children, 91.7% experienced at least 1 micronutrient deficiency, and 64.7% experienced multiple deficiencies. Inflammation (α-1 acid glycoprotein >1 g/L, C-reactive protein >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of deficiency as assessed by retinol, β-carotene, PLP, ferritin, TfR, selenium, copper, or having any or multiple deficiencies. For any nutrient, population deficiency prevalence estimates were altered by ≤5.4% by the presence of inflammation, suggesting that the majority of deficiencies exist regardless of inflammation. Multiple micronutrient deficiencies coexist in school-aged children in rural Nepal, meriting more comprehensive strategies for their assessment and prevention. PMID:24744314

Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients.

PubMed

Kotepui, Manas; Uthaisar, Kwuntida; PhunPhuech, Bhukdee; Phiwklam, Nuoil

2016-04-25

This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, in the western region of Thailand, an endemic region for malaria. Data about patients with malaria hospitalized between 2013 and 2015 were collected. Clinical and sociodemographic characteristics such as age and gender, diagnosis on admission, and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province, Thailand. Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination. Other data such as complete blood count and parasite density were also collected and analyzed. Among the 245 malaria cases, 28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P. vivax infections. Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1 %) patients did not have a G6PD deficiency. Prevalence of male patients with G6PD deficiency was higher than that of female patients (P < 0.05, OR = 5.167). Among the patients with a G6PD deficiency, two (11.8 %) were infected with P. falciparum, while the remaining were infected with P. vivax. Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 10(3)/μL) than those without a G6PD deficiency (0.33 × 10(3)/μL) (P < 0.05, OR = 5.167). Univariate and multivariate analyses also confirmed that malaria patients with a G6PD deficiency have high monocyte counts. The association between G6PD status and monocyte counts was independent of age, gender, nationality, Plasmodium species, and parasite density (P < 0.005). This study showed a prevalence of G6PD deficiency in a malaria-endemic area. This study also supported the assertion that patients with G6PD-deficient red blood cells had no

Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception.

PubMed

Var, Chivorn; Keller, Sheryl; Tung, Rathavy; Freeland, Dylan; Bazzano, Alessandra N

2014-08-26

Hormonal contraceptives may produce side effects that deter women from their use as a method of family planning. In nutritionally vulnerable populations these effects may be more pronounced due to micronutrient deficiencies and health status. Previous studies have been unable to resolve whether micronutrient supplementation may reduce such side effects. In a longitudinal study, 1011 women obtaining oral contraception through the public health system in rural Cambodia were allocated to either intervention or control groups, receiving either daily Vitamin B6 supplement or care as usual (without placebo). The intervention participants (n = 577) reported fewer side effects in three categories: nausea/no appetite, headache, and depression compared with control group participants (n = 434). Women taking Vitamin B6 supplement were less likely to report side effects in a nutritionally vulnerable population. Underlying nutrition status should be considered by clinicians and reproductive health policy makers in the context of providing contraceptive services. Further investigation into micronutrient supplementation, particularly with B6, in reproductive-aged women using hormonal contraception should be conducted in other settings to determine the potential for widespread adoption.

Heat Shock Protein B1-Deficient Mice Display Impaired Wound Healing

PubMed Central

McNamee, Kay; Przybycien, Paulina M.; Lu, Xin; Williams, Richard O.; Bou-Gharios, George; Saklatvala, Jeremy; Dean, Jonathan L. E.

2013-01-01

There is large literature describing in vitro experiments on heat shock protein (hsp)B1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates inflammatory gene expression, and drives cell proliferation. To investigate the function of the protein in vivo we generated hspB1-deficient mice. HspB1-deficient fibroblasts display increased expression of the pro-inflammatory cytokine, interleukin-6, compared to wild-type cells, but reduced proliferation. HspB1-deficient fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27kip1 and p21waf1. The expression of hspB1 protein and mRNA is also controlled by the cell cycle. To investigate the physiological function of hspB1 in regulating inflammation and cell proliferation we used an excisional cutaneous wound healing model. There was a significant impairment in the rate of healing of wounds in hspB1-deficient mice, characterised by reduced re-epithelialisation and collagen deposition but also increased inflammation. HspB1 deficiency augments neutrophil infiltration in wounds, driven by increased chemokine (C-X-C motif) ligand 1 expression. This appears to be a general mechanism as similar results were obtained in the air-pouch and peritonitis models of acute inflammation. PMID:24143227

Pancreatic SEC23B deficiency is sufficient to explain the perinatal lethality of germline SEC23B deficiency in mice

PubMed Central

Khoriaty, Rami; Everett, Lesley; Chase, Jennifer; Zhu, Guojing; Hoenerhoff, Mark; McKnight, Brooke; Vasievich, Matthew P.; Zhang, Bin; Tomberg, Kärt; Williams, John; Maillard, Ivan; Ginsburg, David

2016-01-01

In humans, loss of function mutations in SEC23B result in Congenital Dyserythropoietic Anemia type II (CDAII), a disease limited to defective erythroid development. Patients with two nonsense SEC23B mutations have not been reported, suggesting that complete SEC23B deficiency might be lethal. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration and that mice with hematopoietic SEC23B deficiency do not exhibit CDAII. We now show that SEC23B deficiency restricted to the pancreas is sufficient to explain the lethality observed in mice with global SEC23B-deficiency. Immunohistochemical stains demonstrate an acinar cell defect but normal islet cells. Mammalian genomes contain two Sec23 paralogs, Sec23A and Sec23B. The encoded proteins share ~85% amino acid sequence identity. We generate mice with pancreatic SEC23A deficiency and demonstrate that these mice survive normally, exhibiting normal pancreatic weights and histology. Taken together, these data demonstrate that SEC23B but not SEC23A is essential for murine pancreatic development. We also demonstrate that two BAC transgenes spanning Sec23b rescue the lethality of mice homozygous for a Sec23b gene trap allele, excluding a passenger gene mutation as the cause of the pancreatic lethality, and indicating that the regulatory elements critical for Sec23b pancreatic function reside within the BAC transgenes. PMID:27297878

Effect of Pre-treatment Nutritional Status, Folate and Vitamin B12 Levels on Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia.

PubMed

Tandon, Sneha; Moulik, Nirmalya Roy; Kumar, Archana; Mahdi, Abbas Ali; Kumar, Ashutosh

2015-05-01

To evaluate pre-treatment undernutrition, and folate and B12 deficiency in children with acute lymphoblastic leukemia, and their correlation with complications and outcome of induction chemotherapy. Observational study. Tertiary care teaching hospital in Northern India. 50 children with acute lymphoblastic leukemia. Children were assessed for nutritional status (Weight for age Z-score, serum albumin, folate and B12) at presentation, and were followed-up during induction for bone marrow response, counts and outcome. Folate and B12 were repeated twice at monthly intervals after induction. Univariate and multivariate analyses were done to determine the association of nutritional parameters with the outcome variables. Baseline undernutrition was observed in 66%, hypo-albuminemia in 32.6%, folate deficiency in 41.3% and B12 deficiency in 36.9% of included children. Significant decline in folate levels was noted on serial assays during chemotherapy (P=0.001). Folate deficient children had higher risk for delayed marrow recovery and counts on day 14 (P=0.007 and P=0.001). Hypoalbuminemia (P=0.04), B12 deficiency (P=0.001) and folate (P=0.03) deficiency were associated with toxic deaths during induction. Baseline nutritional deficiencies negatively influence the outcome and occurrence of complications during induction chemotherapy in children with acute lymphoblastic leukemia.

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Vitamin B12 deficiency: what's new?].

PubMed

Braillard, O; Casini, A; Samii, K; Rufenacht, P; Junod, Perron N

2012-09-26

Vitamin B12 screening is only recommended among symptomatic patients or in those with risk factors. The main cause of vitamin B12 deficiency is the food cobalamin malabsorption syndrom. Holotranscobalamin is a more reliable marker than cyanocobalamin to confirm vitamin B12 deficiency, but it has not been validated yet in complex situations. An autoimmune gastritis must be excluded in the absence of risk factors but in the presence of a probable deficiency. Oral substitution treatment is effective but requires excellent therapeutic compliance and close follow-up to monitor the response to treatment. It has not yet been studied among patients suffering from severe symptoms, inflammatory bowel disease and ileal resection.

G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications

PubMed Central

Luzzatto, Lucio; Seneca, Elisa

2014-01-01

That primaquine and other drugs can trigger acute haemolytic anaemia in subjects who have an inherited mutation of the glucose 6-phosphate dehydrogenase (G6PD) gene has been known for over half a century: however, these events still occur, because when giving the drug either the G6PD status of a person is not known, or the risk of this potentially life-threatening complication is under-estimated. Here we review briefly the genetic basis of G6PD deficiency, and then the pathophysiology and the clinical features of drug-induced haemolysis; we also update the list of potentially haemolytic drugs (which includes rasburicase). It is now clear that it is not good practice to give one of these drugs before testing a person for his/her G6PD status, especially in populations in whom G6PD deficiency is common. We discuss therefore how G6PD testing can be done reconciling safety with cost; this is once again becoming of public health importance, as more countries are moving along the pathway of malaria elimination, that might require mass administration of primaquine. Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine. PMID:24372186

Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development.

PubMed

Molloy, Anne M; Kirke, Peadar N; Brody, Lawrence C; Scott, John M; Mills, James L

2008-06-01

The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B12 status have not been sufficiently researched.

The combination of two Sle2 lupus-susceptibility loci and Cdkn2c deficiency leads to T cell-mediated pathology in B6.Faslpr mice

PubMed Central

Xu, Zhiwei; Croker, Byron P.; Morel, Laurence

2013-01-01

The NZM2410 Sle2c1 lupus susceptibility locus is responsible for the expansion of the B1a cell compartment and for the induction of T-cell induced renal and skin pathology on a CD95 deficient (Faslpr)-background. We have previously shown that deficiency in cyclin-dependent kinase inhibitor p18INK4c (p18) was responsible for the B1a cell expansion but was not sufficient to account for the pathology in B6.lpr mice. This study was designed to map the additional Sle2c1 loci responsible for autoimmune pathology when co-expressed with CD95 deficiency. The production, fine-mapping and phenotypic characterization of five recombinant intervals indicated that three interacting sub-loci were responsive for inducting autoimmune pathogenesis in B6.lpr mice. One of these sub-loci corresponds most likely to p18-deficiency. Another major locus mapping to a 2 Mb region at the telomeric end of Sle2c1 is necessary to both renal and skin pathology. Finally, a third locus centromeric to p18 enhances the severity of lupus nephritis. These results provide new insights into the genetic interactions leading to SLE disease presentation, and represent a major step towards the identification of novel susceptibility genes involved in T-cell mediated organ damage. PMID:23698709

[Glucose-6-phosphate dehydrogenase deficiency in Japan].

PubMed

Kanno, Hitoshi; Ogura, Hiromi

2015-07-01

In the past 10 years, we have diagnosed congenital hemolytic anemia in 294 patients, approximately 33% of whom were found to have glucose-6-phosphate dehydrogenase (G6PD) deficiency. It is becoming more common for Japanese to marry people of other ethnic origins, such that G6PD deficiency is becoming more prevalent in Japan. Japanese G6PD deficiency tends to be diagnosed in the neonatal period due to severe jaundice, while G6PD-deficient patients with foreign ancestors tend to be diagnosed at the onset of an acute hemolytic crisis before the age of six. It is difficult to predict the clinical course of each patient by G6PD activity, reduced glutathione content, or the presence/absence of severe neonatal jaundice. We propose that both neonatal G6PD screening and systematic analyses of G6PD gene mutations may be useful for personalized management of patients with G6PD-deficient hemolytic anemia.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest and Sud-Est departments of Haiti.

PubMed

von Fricken, Michael E; Weppelmann, Thomas A; Eaton, Will T; Alam, Meer T; Carter, Tamar E; Schick, Laura; Masse, Roseline; Romain, Jean R; Okech, Bernard A

2014-07-01

Malaria remains a significant public health issue in Haiti, with chloroquine (CQ) used almost exclusively for the treatment of uncomplicated infections. Recently, single dose primaquine (PQ) was added to the Haitian national malaria treatment policy, despite a lack of information on the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency within the population. G6PD deficient individuals who take PQ are at risk of developing drug induced hemolysis (DIH). In this first study to examine G6PD deficiency rates in Haiti, 22.8% (range 14.9%-24.7%) of participants were found to be G6PD deficient (class I, II, or III) with 2.0% (16/800) of participants having severe deficiency (class I and II). Differences in deficiency were observed by gender, with males having a much higher prevalence of severe deficiency (4.3% vs. 0.4%) compared to females. Male participants were 1.6 times more likely to be classified as deficient and 10.6 times more likely to be classified as severely deficient compared to females, as expected. Finally, 10.6% (85/800) of the participants were considered to be at risk for DIH. Males also had much higher rates than females (19.3% vs. 4.6%) with 4.9 times greater likelihood (p value 0.000) of having an activity level that could lead to DIH. These findings provide useful information to policymakers and clinicians who are responsible for the implementation of PQ to control and manage malaria in Haiti. Copyright © 2014 Elsevier B.V. All rights reserved.

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency.

PubMed

Pao, Mritunjay; Kulkarni, Anjali; Gupta, Vidya; Kaul, Sushma; Balan, Saroja

2005-10-01

This study was carried out to detect the incidence of erythrocytic Glucose-6 -Phosphate dehydrogenase (G-6-PD) deficiency, to compare the incidence of hyperbilirubinemia in G-6-PD deficient neonates as compared to G-6-PD normal neonates and to asses the usefulness of neonatal screening for G-6-PD deficiency. In a retrospective hospital based study 2,479 male and female neonates consecutively born at Indraprastha Apollo hospital between July 1998 to June 2003 who were screened for G-6-PD levels were evaluated for the incidence of G-6-PD deficiency. Incidence of G-6-PD deficiency was found to be 2.0%. Incidence in males was 283% and female was 1.05%. The incidence of hyperbilirubinemia was found to be 32% in G-6-PD deficient neonates which was significantly higher than the incidence of hyperbilirubinemia in neonates with normal G-6-PD, which was 12.3% (P< 0.001). Our data suggests that neonatal screening for G-6-PD deficiency is a useful test for preventing and early treatment of complications associated with it.

Simultaneous occurrence of hereditary C6 and C2 deficiency in a French-Canadian family.

PubMed

Delâge, J M; Lehner-Netsch, G; Lafleur, R; Simard, J; Brun, G; Prochazka, E

1979-06-01

The sera of four sisters were found to lack the sixth component of complement (C6) and the serum of one was also partially deficient in the second component (C2). Two other blood relatives were found to be heterozygous for both deficiencies, while only one sibling had normal values. The father of these eight siblings was heterozygous for C2D and C6D and in the third generation, six children were heterozygous for C6 deficiency was treated for chronic active brucel-transmitted; the C6 deficiency was not linked to the HLA system, while the C2-deficiency segregated with the haplotype A10,B18. The proband, homozygous for C6 deficiency was treated for chronic active Brucellosis and in another sibling with C6 deficiency, toxoplasmosis was diagnosed. Neither bleeding disorders nor a tendency to collagen diseases have been observed and the opsonic activity was normal in the sera of all family members.

Simultaneous occurrence of hereditary C6 and C2 deficiency in a French-Canadian family.

PubMed Central

Delâge, J M; Lehner-Netsch, G; Lafleur, R; Simard, J; Brun, G; Prochazka, E

1979-01-01

The sera of four sisters were found to lack the sixth component of complement (C6) and the serum of one was also partially deficient in the second component (C2). Two other blood relatives were found to be heterozygous for both deficiencies, while only one sibling had normal values. The father of these eight siblings was heterozygous for C2D and C6D and in the third generation, six children were heterozygous for C6 deficiency was treated for chronic active brucel-transmitted; the C6 deficiency was not linked to the HLA system, while the C2-deficiency segregated with the haplotype A10,B18. The proband, homozygous for C6 deficiency was treated for chronic active Brucellosis and in another sibling with C6 deficiency, toxoplasmosis was diagnosed. Neither bleeding disorders nor a tendency to collagen diseases have been observed and the opsonic activity was normal in the sera of all family members. PMID:468307

Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

PubMed Central

Harrington, Janas; Cadogan, Sharon; Honari, Bahman; Perera, Kanthi; Fitzgerald, Anthony P.; Perry, Ivan J.; Cahill, Mary R.

2013-01-01

Objective To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. Methods A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). Results The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland

Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates.

PubMed

Bayoumi, R A; Nur-E-Kamal, M S; Tadayyon, M; Mohamed, K K; Mahboob, B H; Qureshi, M M; Lakhani, M S; Awaad, M O; Kaeda, J; Vulliamy, T J; Luzzatto, L

1996-01-01

In a cross-sectional study, the activity, electrophoretic mobility and genotypes of glucose-6-phosphate dehydrogenase (G6PD) were determined among healthy, UAE national school boys from Al-Ain District in the United Arab Emirates, The prevalence of G6PD deficiency in this population sample was 11%. The majority of G6PD-deficient subjects were descendants of Omani, Baluchi or Yemeni migrants. Of 18 deficient subjects, 16 had an enzyme activity of < 10% of normal while 2 had an activity of just above 10%. Electrophoresis was performed on 166 samples and showed that, apart from deficient samples, all had the normal mobility of G6PD type B. Of the 18 deficient subjects, 14 had the B type mobility of G6PD Mediterranean and 4 had the A type mobility of G6PD A-. Genotyping demonstrated that 10 had the Mediterranean mutation while 3 had the A- mutation, consistent with their electrophoretic mobility. Another 3 had the G6PD Aures mutation, recently described as polymorphic in Algeria and Spain. The mutations in the remaining 2 subjects have not yet been identified.

How prevalent is vitamin B(12) deficiency among vegetarians?

PubMed

Pawlak, Roman; Parrott, Scott James; Raj, Sudha; Cullum-Dugan, Diana; Lucus, Debbie

2013-02-01

Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. The goal of the present literature review was to assess the rate of B12 depletion and deficiency among vegetarians and vegans. Using a PubMed search to identify relevant publications, 18 articles were found that reported B12 deficiency rates from studies that identified deficiency by measuring methylmalonic acid, holo-transcobalamin II, or both. The deficiency rates reported for specific populations were as follows: 62% among pregnant women, between 25% and almost 86% among children, 21-41% among adolescents, and 11-90% among the elderly. Higher rates of deficiency were reported among vegans compared with vegetarians and among individuals who had adhered to a vegetarian diet since birth compared with those who had adopted such a diet later in life. The main finding of this review is that vegetarians develop B12 depletion or deficiency regardless of demographic characteristics, place of residency, age, or type of vegetarian diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12. © 2012 International Life Sciences Institute.

Involvement of Vitamin B6 Biosynthesis Pathways in the Insecticidal Activity of Photorhabdus luminescens.

PubMed

Sato, Kazuki; Yoshiga, Toyoshi; Hasegawa, Koichi

2016-06-15

Photorhabdus luminescens is a Gram-negative entomopathogenic bacterium which symbiotically associates with the entomopathogenic nematode Heterorhabditis bacteriophora P. luminescens is highly virulent to many insects and nonsymbiotic nematodes, including Caenorhabditis elegans To understand the virulence mechanisms of P. luminescens, we obtained virulence-deficient and -attenuated mutants against C. elegans through a transposon-mutagenized library. From the genetic screening, we identified the pdxB gene, encoding erythronate-4-phosphate dehydrogenase, as required for de novo vitamin B6 biosynthesis. Mutation in pdxB caused growth deficiency of P. luminescens in nutrient-poor medium, which was restored under nutrient-rich conditions or by supplementation with pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 Supplementation with three other B6 vitamers (pyridoxal, pyridoxine, and pyridoxamine) also restored the growth of the pdxB mutant, suggesting the existence of a salvage pathway for vitamin B6 biosynthesis in P. luminescens Moreover, supplementation with PLP restored the virulence-deficient phenotype against C. elegans Combining these results with the fact that pdxB mutation also caused attenuation of insecticidal activity, we concluded that the production of appropriate amounts of vitamin B6 is critical for P. luminescens pathogenicity. The Gram-negative entomopathogenic bacterium Photorhabdus luminescens symbiotically associates with the entomopathogenic nematode Heterorhabditis bacteriophora P. luminescens is highly virulent to many insects and nonsymbiotic nematodes, including Caenorhabditis elegans We have obtained several virulence-deficient and -attenuated P. luminescens mutants against C. elegans through genetic screening. From the genetic analysis, we present the vitamin B6 biosynthetic pathways in P. luminescens that are important for its insecticidal activity. Mutation in pdxB, encoding erythronate-4-phosphate dehydrogenase and required for

Deficient selenium status of a healthy adult Spanish population.

PubMed

Millán Adame, E; Florea, D; Sáez Pérez, L; Molina López, J; López-González, B; Pérez de la Cruz, A; Planells del Pozo, E

2012-01-01

Selenium is an essential micronutrient for human health, being a cofactor for enzymes with antioxidant activity that protect the organism from oxidative damage. An inadequate intake of this mineral has been associated with the onset and progression of chronic diseases such as hypertension, diabetes, coronary diseases, asthma, and cancer. For this reason, knowledge of the plasma and erythrocyte selenium levels of a population makes a relevant contribution to assessment of its nutritional status. The objective of the present study was to determine the nutritional status of selenium and risk of selenium deficiency in a healthy adult population in Spain by examining food and nutrient intake and analyzing biochemical parameters related to selenium metabolism, including plasma and erythrocyte levels and selenium-dependent glutathione peroxidase (GPx) enzymatic activity. We studied 84 healthy adults (31 males and 53 females) from the province of Granada, determining their plasma and erythrocyte selenium concentrations and the association of these levels with the enzymatic activity of glutathione peroxidase (GPx) and with life style factors. We also gathered data on their food and nutrient intake and the results of biochemical analyses. Correlations were studied among all of these variables. The mean plasma selenium concentration was 76.6 ± 17.3 μg/L (87.3 ± 17.4 μg/L in males, 67.3 ± 10.7 μg/L in females), whereas the mean erythrocyte selenium concentration was 104.6 μg/L (107.9 ± 26.1 μg/L in males and 101.7 ± 21.7 μg/L in females). The nutritional status of selenium was defined by the plasma concentration required to reach maximum GPx activity, establishing 90 μg/L as reference value. According to this criterion, 50% of the men and 53% of the women were selenium deficient. Selenium is subjected to multiple regulation mechanisms. Erythrocyte selenium is a good marker of longer term selenium status, while plasma selenium appears to be a marker of short

Vitamin B12 deficiency presenting as acute ataxia

PubMed Central

Crawford, John Ross; Say, Daphne

2013-01-01

A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient. PMID:23536622

Vitamin B12 deficiency presenting as acute ataxia.

PubMed

Crawford, John Ross; Say, Daphne

2013-03-26

A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.

Glucose-6-phosphate dehydrogenase deficiency and sickle cell genes in Bisha.

PubMed

el-Hazmi, M A; al-Swailem, A; Warsy, A S

1995-08-01

This study was conducted on 820 Saudi males and females from Bisha in the western province of Saudi Arabia. Blood samples were analysed to determine the frequency of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S (Hb S) genes, and to investigate interactions between the two genes. Severe G-6-PD deficiency in this population was due to G-6-PD-Mediterranean; the African variant G-6-PD-A- was not detected. The normal and common form of the enzyme was G-6-PD-B+, occurring at a frequency of 0.8444 and 0.8177 in males and females, respectively. Variants included G-6-PD-A+, G-6-PD-Mediterranean, and G-6-PD-Mediterranean-like at frequencies of 0.0043, 0.0767, and 0.0746, respectively, in males and 0.0057, 0.05413, and 0.0855, respectively, in females. Sickle cell haemoglobin (Hb S) was encountered in the homozygous (4 per cent) and heterozygous (10 per cent) states at a gene frequency of 0.0860. No interaction between G-6-PD deficiency and Hb S gene was observed. A severe haematological and clinical presentation of the Hb SS disease was encountered in the children from Bisha.

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

PubMed

Brito, Alex; Grapov, Dmitry; Fahrmann, Johannes; Harvey, Danielle; Green, Ralph; Miller, Joshua W; Fedosov, Sergey N; Shahab-Ferdows, Setareh; Hampel, Daniela; Pedersen, Theresa L; Fiehn, Oliver; Newman, John W; Uauy, Ricardo; Allen, Lindsay H

2017-08-09

Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized. Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion. Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated. Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 ( P < 0.001), and reduced tHcy and serum MMA ( P < 0.001). Metabolomic changes from before to after treatment included increases ( P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism-that is, methionine and cysteine-were reduced ( P < 0.001). Direct significant correlations ( P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function

Evaluation of the Diagnostic Accuracy of CareStart G6PD Deficiency Rapid Diagnostic Test (RDT) in a Malaria Endemic Area in Ghana, Africa

PubMed Central

Adu-Gyasi, Dennis; Asante, Kwaku Poku; Newton, Sam; Dosoo, David; Amoako, Sabastina; Adjei, George; Amoako, Nicholas; Ankrah, Love; Tchum, Samuel Kofi; Mahama, Emmanuel; Agyemang, Veronica; Kayan, Kingsley; Owusu-Agyei, Seth

2015-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) as a point-of-care tool for screening G6PD deficiency. Methods A cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the “gold standard”. Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval. Results The sensitivity (SE) and specificity (SP) of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199) change on the performance of the G6PD RDT test kit compared to the “gold standard”. Conclusions The outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy. PMID:25885097

Evaluation of the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) in a malaria endemic area in Ghana, Africa.

PubMed

Adu-Gyasi, Dennis; Asante, Kwaku Poku; Newton, Sam; Dosoo, David; Amoako, Sabastina; Adjei, George; Amoako, Nicholas; Ankrah, Love; Tchum, Samuel Kofi; Mahama, Emmanuel; Agyemang, Veronica; Kayan, Kingsley; Owusu-Agyei, Seth

2015-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) as a point-of-care tool for screening G6PD deficiency. A cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the "gold standard". Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval. The sensitivity (SE) and specificity (SP) of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199) change on the performance of the G6PD RDT test kit compared to the "gold standard". The outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy.

G6PD Deficiency (Glucose-6-Phosphate Dehydrogenase) (For Parents)

MedlinePlus

... In rare cases, G6PD deficiency leads to chronic anemia . With the right precautions, a child with G6PD deficiency can lead a healthy and ... to rule out other possible causes of the anemia. If you feel that your child may be at risk because of either a ...

Markers of vitamin B6 status and metabolism as predictors of incident cancer: the Hordaland Health Study.

PubMed

Zuo, Hui; Ueland, Per M; Eussen, Simone J P M; Tell, Grethe S; Vollset, Stein E; Nygård, Ottar; Midttun, Øivind; Meyer, Klaus; Ulvik, Arve

2015-06-15

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'-phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3-hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4-pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community-based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998-99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site-specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow-up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate-adjusted Cox-regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) = 1.31 (1.12-1.52) per two standard deviation (SD) increment (p < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) = 2.46 (1.49-4.05) per two SD increment (p < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Restoring balance to B cells in ADA deficiency.

PubMed

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease?

PubMed

Albayrak, Canan; Albayrak, Davut

2015-03-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study

USDA-ARS?s Scientific Manuscript database

Background: Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved. Objective: Our objective was to examine the cross-sectional association of ...

Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6 in rats.

PubMed

Gmoshinsky, I V; Vrzhesinskaya, O A; Shumakova, A A; Shipelin, V A; Kodentsova, V M; Khotimchenko, S A

2016-01-01

Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a food additive E551 in many enriched foods and food supplements. The aim of this study was to evaluate the effect of oral administration of SiO2 NPs on assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats. Amorphous SiO2 «Orisil-300 ®» was used with the size of the primary NPs 20-60 nm according to the electronic, atomic force microscopy and dynamic light scattering. The experiment was conducted on 8 groups of growing male Wistar rats (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14 and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through­out the experiment balanced semi-synthetic diet. Animals of the 2nd group received a diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and 8th groups -the same diet from the 1st to the 21th day, and then, before the closure of the experiment, the diet provided with the indicated B vitamins at 100% of normal level. From day 22 of experiment and until the end at day 29 the animals of the 3rd and 6th groups received deionized water (placebo) through intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2 dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day. Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter­mined by fluorimetric methods. It was found that rats in group 2 lagged in weight gain at day 21 significantly compared to group 1, and developed a marked deficiency of vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6 to 8 at day 29 par­tial recovery was achieved in vitamin status. Administration of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had no significant effect on any param­eters of vitamin status in comparison to group 3. However

Vitamin E Deficiency and Oxidative Status are Associated with Prediabetes in Apparently Healthy Subjects.

PubMed

Rodríguez-Ramírez, Gabriela; Simental-Mendía, Luis E; Carrera-Gracia, Manuela de la A; Quintanar-Escorza, Martha-Angélica

2017-04-01

Previous studies have indicated that vitamin E deficiency and oxidative stress affect the beta cell function. Hence, the aim of this study was to determine the association between vitamin E deficiency and oxidative status with prediabetes in apparently healthy subjects. Apparently healthy men and women aged 18-65 years were enrolled in a case-control study. Individuals with new diagnosis of prediabetes were considered as cases and compared with a control group of individuals with normal glucose tolerance. Smoking, alcohol intake, pregnancy, diabetes, kidney disease, liver disease, cardiovascular disease, malignancy, glucocorticoid treatment and consumption of lipid-lowering drugs, antioxidants and vitamin supplements were exclusion criteria. Vitamin E deficiency was defined by serum levels of α-tocopherol <11.6 μmol/L, oxidative status was assessed by total antioxidant capacity and lipid peroxidation, and prediabetes was considered by the presence of impaired fasting glucose and/or impaired glucose tolerance. A total of 148 subjects were allocated into the case (n = 74) and control (n = 74) groups. The frequency of vitamin E deficiency was higher in the case group (41.8%) compared with the control group (35.1%), p = 0.03. The logistic regression analysis adjusted by age, waist circumference and body mass index, revealed a significant association between vitamin E deficiency (OR 3.23; 95% CI: 1.34-7.79, p = 0.009), lipoperoxidation (OR 2.82; CI 95%: 1.42-5.59, p = 0.003) and total antioxidant capacity (OR 0.93; CI 95%: 0.90-0.96, p <0.001) with prediabetes. Results of the present study suggest that both vitamin E deficiency and oxidative status are associated with prediabetes in apparently healthy subjects. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Vitamin B6 metabolism in microbes and approaches for fermentative production.

PubMed

Rosenberg, Jonathan; Ischebeck, Till; Commichau, Fabian M

Vitamin B6 is a designation for the six vitamers pyridoxal, pyridoxine, pyridoxamine, pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate, and pyridoxamine. PLP, being the most important B6 vitamer, serves as a cofactor for many proteins and enzymes. In contrast to other organisms, animals and humans have to ingest vitamin B6 with their food. Several disorders are associated with vitamin B6 deficiency. Moreover, pharmaceuticals interfere with metabolism of the cofactor, which also results in vitamin B6 deficiency. Therefore, vitamin B6 is a valuable compound for the pharmaceutical and the food industry. Although vitamin B6 is currently chemically synthesized, there is considerable interest on the industrial side to shift from chemical processes to sustainable fermentation technologies. Here, we review recent findings regarding biosynthesis and homeostasis of vitamin B6 and describe the approaches that have been made in the past to develop microbial production processes. Moreover, we will describe novel routes for vitamin B6 biosynthesis and discuss their potential for engineering bacteria that overproduce the commercially valuable substance. We also highlight bottlenecks of the vitamin B6 biosynthetic pathways and propose strategies to circumvent these limitations. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency.

PubMed

Nguyen, Thi Phuong Mai; Nguyen, Thu Hien; Ngo, Diem Ngoc; Vu, Chi Dung; Nguyen, Thi Kim Lien; Nong, Van Hai; Nguyen, Huy Hoang

2015-07-10

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5 years old at 2 years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription. Copyright © 2015 Elsevier B.V. All rights reserved.

Inverse Association between Glucose‒6‒Phosphate Dehydrogenase Deficiency and Hepatocellular Carcinoma

PubMed

Dore, Maria Pina; Vidili, Gianpaolo; Marras, Giuseppina; Assy, Silas; Pes, Giovanni Mario

2018-04-27

Background: Studies in experimental models and humans suggest that glucose‒6‒phosphate dehydrogenase (G6PD) deficiency, an inherited condition, may be inversely related to hepatocellular carcinoma (HCC). We tested this hypothesis in a large cohort of Sardinian patients. Methods: A case-control study was performed using data from 11,143 records of patients who underwent upper endoscopy between 2002 and 2017. Gender, age, G6PD status and information regarding the presence of HCC, were recorded. Cases (HCC positive) and controls (HCC negative) were compared for the presence of G6PD deficiency adjusting for major HCC risk factors using logistic regression. Results: Overall, 114 HCC cases and 11,029 controls were identified. G6PD deficiency was detected in 11.5% of study participants, and was associated with a reduced risk of HCC [odds ratio (OR); 0.451; 95% confidence interval (CI), 0.207−0.982] after adjusting for all covariates. Factors significantly associated with HCC were cirrhosis (OR, 23.30; 95% CI, 11.48−47.25), diabetes (OR, 2.396; 95% CI, 1.449−3.963), among infection hepatitis HBV with an OR of 2.326, age ≥65 years (OR, 1.941; 95% CI, 1.234−2.581) and male gender (OR, 1.611; 95% CI, 1.006−3.081). Conclusions: Our study revealed a significant inverse association between G6PD deficiency and risk of HCC. These findings need to be confirmed in further studies. Creative Commons Attribution License

Nutritional Deficiencies in Chinese Patients Undergoing Gastric Bypass and Sleeve Gastrectomy: Prevalence and Predictors.

PubMed

Guan, Bingsheng; Yang, Jingge; Chen, Yanya; Yang, Wah; Wang, Cunchuan

2018-05-12

Nutritional deficiencies have been reported in bariatric surgery patients with inconsistent results. However, scarce data exist for Chinese patients. We aimed to assess nutritional deficiencies in Chinese patients undergoing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), and to identify predictors of postoperative nutritional status. A retrospective review of a prospectively collected database was conducted in the patients undergoing RYGB and SG in our hospital between June 2013 and January 2017. Anthropometric data and nutritional data were collected before surgery, at 6 and 12 months postoperatively. This study enrolled 269 patients (120 RYGB, 149 SG). Nutritional deficiencies were common in Chinese bariatric candidates, with vitamin D deficiency the most serious (78.8%), followed by vitamin B1 (39.2%), vitamin B6 (28.0%), folate (26.8%), vitamin C (18.0%) albumin (13.4%), transferrin (11.6%), and phosphorus (11.5%). Despite postoperative routine multivitamin and calcium supplements, nutritional deficiencies were still obvious for RYGB and SG patients. The prevalence of hemoglobin and vitamin B12 deficiencies increased remarkably in the RYGB group; the levels of hemoglobin, globin, vitamin B12, and ferritin decreased significantly (P < 0.05). Preoperative hemoglobin, vitamin B12, and ferritin levels were independently associated with postoperative decrease, respectively. Deficiencies of vitamin D, vitamin B1, vitamin B6, vitamin C, and albumin before surgery were predictors for deficiencies 1 year after surgery, respectively. Nutritional deficiencies are common in Chinese bariatric surgery candidates. Similar deficiencies were also seen after RYGB and SG. Routine evaluation and related corrections of preoperative nutritional abnormity could contribute to postoperative nutrient balance.

Glucose-6-phosphate dehydrogenase deficiency in internationally adopted children.

PubMed

Spring, Rachel; Schlaack, Hanna; Rice, Marilyn; Staat, Mary A; Quinn, Charles T

2018-05-01

There are conflicting guidelines about screening of internationally adopted children for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic disorder. In a multi-ethnic population of 2,169 internationally adopted children, we found that the prevalence of G6PD deficiency was 1.6% overall and 2.2% in males. Prevalence differed by country or region of origin, ranging from 0 to 13% overall and 0 to 22% in males. The prevalence in females was 1%. A diagnosis of G6PD deficiency informs the treatment of malaria and enables education and counseling to prevent morbidity and mortality from G6PD deficiency. Screening for G6PD deficiency should be strongly considered for internationally adopted children. © 2018 Wiley Periodicals, Inc.

Inflammation, vitamin B6 and related pathways.

PubMed

Ueland, Per Magne; McCann, Adrian; Midttun, Øivind; Ulvik, Arve

2017-02-01

The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), serves as a co-factor in more than 150 enzymatic reactions. Plasma PLP has consistently been shown to be low in inflammatory conditions; there is a parallel reduction in liver PLP, but minor changes in erythrocyte and muscle PLP and in functional vitamin B6 biomarkers. Plasma PLP also predicts the risk of chronic diseases like cardiovascular disease and some cancers, and is inversely associated with numerous inflammatory markers in clinical and population-based studies. Vitamin B6 intake and supplementation improve some immune functions in vitamin B6-deficient humans and experimental animals. A possible mechanism involved is mobilization of vitamin B6 to the sites of inflammation where it may serve as a co-factor in pathways producing metabolites with immunomodulating effects. Relevant vitamin B6-dependent inflammatory pathways include vitamin B6 catabolism, the kynurenine pathway, sphingosine 1-phosphate metabolism, the transsulfuration pathway, and serine and glycine metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence of Vitamin B12 and Folate Deficiency in School Children Residing at High Altitude Regions in India.

PubMed

Gupta, Aakriti; Kapil, Umesh; Ramakrishnan, Lakshmy; Pandey, Ravindra Mohan; Yadav, Chander Prakash

2017-04-01

To assess the prevalence of vitamin B 12 and folate deficiencies among children residing at high altitude regions of Himachal Pradesh, India. A total of 215 school children in the age group of 6-18 y were included. Biochemical estimation of serum vitamin B 12 and folate levels was undertaken using chemiluminescence immunoassay method. The consumption pattern of foods high in dietary vitamin B 12 and folate was recorded using Food Frequency Questionnaire. The median levels (interquartile range) of serum vitamin B 12 and folate were 326 (259-395) pg/ml and 7.7 (6-10) ng/ml respectively. The prevalence of vitamin B 12 and folate deficiency amongst school age children was found as 7.4% and 1.5% respectively. A low prevalence of vitamin B 12 and folate deficiencies was found amongst children aged 6-18 y living at high altitude regions in India. This is possibly due to high frequency of consumption of foods rich in vitamin B 12 and folate.

[G6PD deficiency among children under 7 years old from Yunnan with unique ethnic minority origin].

PubMed

Yao, Li-qin; Zou, Tuan-biao; Wang, Xing-tian; Quan, Xing; Chen, Qian; Yang, Fa-bin; Hu, Li-sha; Fan, Li-mei; Wang, Min; Feng, Xi-yun; Liu, Jin-tao; Zhao, Zhong-ming

2013-04-01

To investigate the epidemiological status of glucose-6-phosphate dehydrogenase (G6PD) deficiency among children from Yunnan with unique ethnic origins. DNA samples from 11759 children were tested with fluorescent spot test, G6PD/6PGD quantitative ratio assay and hemoglobin electrophoresis. The detection rate of G6PD deficiency was 2.5%, for which boys were significantly greater than girls (3.5% vs. 1.4%, P<0.05). Significant differences were also detected among children from different ethnic groups and different regions. For ethnic Han Chinese, the detection rate was 0.7%, which was lower than the majority of ethnic minorities. By regression analysis, altitude of residence and family history both have significant influence on the calculated rate. Occurrence of G6PD deficiency seems to be influenced by gender. It also varies substantially between different ethnic groups as well as regions, e.g., more common in south. It also showed a declining trend after years of diagnosis and intervention. This survey may provide a valuable basis for counseling of G6PD deficiency in Yunnan.

Glucose-6-phosphate dehydrogenase deficiency and the sickle cell gene in Makkah, Saudi Arabia.

PubMed

el-Hazmi, M A; Warsy, A S; Bahakim, H H; al-Swailem, A

1994-02-01

This study was conducted on 689 Saudi males and females living in the Makkah area in the western province of Saudi Arabia. The frequency of severe glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in the male and female populations was 0.055 and 0.042 respectively. The normal G-6-PD was G-6-PD-B+ and the G-6-PD phenotypes identified included G-6-PD-A+, G-6-PD-A-, G-6-PD-Mediterranean, and G-6-PD-Mediterranean-like at gene frequencies of 0.0288, 0.0026, 0.05497, and 0.1969 in the male population and 0.026, 0.0146, 0.0407, and 0.02606 in the female population. The main variants producing severe and mild G-6-PD deficiency were G-6-PD-Mediterranean and G-6-PD-Mediterranean-like, respectively. The sickle cell gene was identified at a frequency of 0.029 and no interaction between sickle cell and G-6-PD deficiency genes was encountered.

Vitamin status in elderly people in relation to the use of nutritional supplements.

PubMed

Fabian, E; Bogner, M; Kickinger, A; Wagner, K H; Elmadfa, I

2012-03-01

This study aimed to evaluate the status of several vitamins and to investigate the effect of regular individual supplementation on their status in this population. An observational study. State of Burgenland, Austria. A total of 102 non-institutionalized subjects (49% supplementing regularly, 51% without supplementation) aged between 70-90 years were recruited. Plasma levels of vitamins A, D, E, K and C were determined by HPLC. The functional parameters of vitamins B1, B2 and B6, i.e. the activities of the erythrocyte enzymes transketolase, glutathione reductase and glutamic oxaloacetic transaminase, were analyzed photometrically; plasma folate and vitamin B12 were determined by RIA. The status of vitamins A, E and C was generally satisfactory. Eighty-eight percent and 42% of participants were deficient in vitamins D and K, respectively, as were 29% for B6; up to 10% of participants were deficient in vitamins B1, B2, B12 and folate. A considerable percentage of participants was, however, at risk for vitamin deficiencies (vitamins B1, B6, B12, folate: 20-30%, vitamin B2: 60%). Except for vitamins A and K, regular intake of supplements had a significant positive influence on vitamin levels. These results indicate that use of supplements significantly improved the status of several vitamins in elderly people. Due to age-related problems concerning the intake and digestion of nutrients, a moderate, regular supplementation might be a useful option for older people who are otherwise unable to satisfy their micronutrient requirements.

High Serum Folate Is Associated with Brain Atrophy in Older Diabetic People with Vitamin B12 Deficiency.

PubMed

Deng, Y; Wang, D; Wang, K; Kwok, T

2017-01-01

Previous studies have reported the adverse cognitive effects of high folate status in older individuals with vitamin B12 (VB12) deficiency. Thus, the aim of this study was to investigate how high serum folate and VB12 deficiency could collaboratively aggravate neuronal degeneration. In total, 146 older non-demented diabetic individuals with an average age of 75 ± 3.9 were recruited. VB12 deficiency and high folate status were based on high serum methylmalonic acid (MMA) concentrations (> 0.3 μmol/L) and the serum folate concentration being in the top tertile (> 31.4 nmol/L) respectively. Among these subjects, there were 20 with elevated MMA and high folate. The structural magnetic resonance imaging data of these subjects were analyzed by performing flexible factorial analysis with the "folate level" and "MMA level" added as main effects, and the interaction effect of folate and VB12 on brain volume was evaluated. The results showed significant gray matter atrophy of the right middle occipital gyrus and the opercular part of the inferior frontal gyrus in subjects with a simultaneous high folate status and VB12 deficiency. Together with previous observational studies on cognitive function, this study lends support to the notion that high serum folate concentrations in older people with VB12 deficiency may be associated with increased neurodegeneration.

Short-Term Vitamin B-6 Restriction Does Not Affect Plasma Concentrations of Hydrogen Sulfide Biomarkers Lanthionine and Homolanthionine in Healthy Men and Women.

PubMed

DeRatt, Barbara N; Ralat, Maria A; Gregory, Jesse F

2016-03-09

Suboptimal vitamin B-6 status is associated with increased cardiovascular disease risk, although the mechanism is unknown. The synthesis of the vasodilator hydrogen sulfide occurs through side reactions of the transsulfuration enzymes cystathionine β-synthase and cystathionine γ-lyase, with pyridoxal 5'-phosphate as a coenzyme. Two proposed hydrogen sulfide biomarkers, lanthionine and homolanthionine, are produced concurrently. To determine whether hydrogen sulfide production is reduced by vitamin B-6 deficiency, we examined the relations between plasma concentrations of lanthionine and homolanthionine, along with other components of the transsulfuration pathway (homocysteine, cystathionine, and Cys), in a secondary analysis of samples from 2 vitamin B-6 restriction studies in healthy men and women. Metabolite concentrations were measured in plasma from 23 healthy adults (12 men and 11 women) before and after 28-d controlled dietary vitamin B-6 restriction (0.37 ± 0.04 mg/d). Vitamin B-6 restriction effects on lanthionine and homolanthionine concentrations were assessed. Associations between hydrogen sulfide biomarkers, transsulfuration metabolites, and functional indicators of vitamin B-6 deficiency were analyzed by linear regression. Preprandial plasma lanthionine and homolanthionine concentrations ranged from 89.0 to 372 nmol/L and 5.75 to 32.3 nmol/L, respectively, in healthy adults. Mean lanthionine and homolanthionine concentrations were not affected by vitamin B-6 restriction (P < 0.66), with marked heterogeneity of individual responses. After restriction, homolanthionine was positively associated with functional indicators of vitamin B-6 deficiency, which differed from hypothesized negative associations. Plasma lanthionine was positively correlated with the concentration of its precursor, Cys, before (R 2 = 0.36; P = 0.002) and after (R 2 = 0.37; P = 0.002) restriction. Likewise, homolanthionine concentration was positively correlated with its precursor

Overview of the nutritional status of selected micronutrients in Mexican children in 2006.

PubMed

Shamah-Levy, Teresa; Villalpando, Salvador; Jáuregui, Alejandra; Rivera, Juan A

2012-01-01

To present an overview of micronutrient status of Mexican children in 2006. Data on iron, zinc, folate and vitamin B12 deficiencies and low serum copper and magnesium were gathered and critically analyzed from the 2006 National Health and Nutrition Survey. Iron deficiency is still the main nutritional deficiency in children (13%-26%). Zinc deficiency was high in all age groups (≈25%) but reduced 5.6 PP in children <5 y from 1999 to 2006. Folate deficiency was 3.2% and vitamin B12 deficiency 7.7% in children. Low serum magnesium and copper were high (22.6% and 30.6%, respectively). The prevalence of iron deficiency seems to be lowering, and zinc deficiency has reduced in Mexican children. A high prevalence of copper and magnesium deficiencies warrants further research on their public health implications.

Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of Life

PubMed Central

Varsi, Kristin; Bolann, Bjørn; Torsvik, Ingrid; Rosvold Eik, Tina Constanse; Høl, Paul Johan; Bjørke-Monsen, Anne-Lise

2017-01-01

Pregnant women and infants are at risk for selenium deficiency, which is known to have negative effects on immune and brain function. We have investigated selenium levels in 158 healthy never-pregnant women and in 114 pregnant and lactating women and their infants at age 6 months and related this to clinical outcomes during the first 6 months of life. Neurodevelopment was assessed with the parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium level ≤0.90 µmol/L in pregnancy week 18 was negatively related to infant neurodevelopment at 6 months (B = −20, p = 0.01), whereas a selenium level ≤0.78 µmol/L in pregnancy week 36 was associated with an increased risk (odds ratio 4.8) of having an infant infection during the first 6 weeks of life. A low maternal selenium status in pregnancy was found to be associated with an increased risk of infant infection during the first 6 weeks of life and a lower psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium deficiency of 0.90 µmol/L in pregnancy week 18 and 0.78 µmol/L in pregnancy week 36. This should be reevaluated in an intervention study. PMID:28492511

Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of Life.

PubMed

Varsi, Kristin; Bolann, Bjørn; Torsvik, Ingrid; Rosvold Eik, Tina Constanse; Høl, Paul Johan; Bjørke-Monsen, Anne-Lise

2017-05-11

Pregnant women and infants are at risk for selenium deficiency, which is known to have negative effects on immune and brain function. We have investigated selenium levels in 158 healthy never-pregnant women and in 114 pregnant and lactating women and their infants at age 6 months and related this to clinical outcomes during the first 6 months of life. Neurodevelopment was assessed with the parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium level ≤0.90 µmol/L in pregnancy week 18 was negatively related to infant neurodevelopment at 6 months (B = -20, p = 0.01), whereas a selenium level ≤0.78 µmol/L in pregnancy week 36 was associated with an increased risk (odds ratio 4.8) of having an infant infection during the first 6 weeks of life. A low maternal selenium status in pregnancy was found to be associated with an increased risk of infant infection during the first 6 weeks of life and a lower psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium deficiency of 0.90 µmol/L in pregnancy week 18 and 0.78 µmol/L in pregnancy week 36. This should be reevaluated in an intervention study.

Chronic transgenerational vitamin B12 deficiency of severe and moderate magnitudes modulates adiposity-probable underlying mechanisms.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Muralikrishna, Bojanapalli; Putcha, Uday Kumar; Raghunath, Manchala

2017-05-06

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Evaluation of the phenotypic test and genetic analysis in the detection of glucose-6-phosphate dehydrogenase deficiency.

PubMed

Nantakomol, Duangdao; Paul, Rick; Palasuwan, Attakorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika

2013-08-21

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is particularly prevalent in historically malaria-endemic countries. Although most individuals with G6PD deficiency are asymptomatic, deficiency can result in acute haemolytic anaemia after exposure to oxidative agents. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis following, for example, anti-malarial treatment. The aim of this study was to investigate which method was the best predictor of this disorder. The present study investigated four G6PD activity detections (fluorescence spot (FS), methaemoglobin reduction (MR), biochemical and cytochemical test). These methods accompanied with mutation analysis of blood samples were taken from 295 apparently healthy individuals with unknown G6PD deficiency status. Molecular characterization of 295 Thai adults revealed an overall prevalence of 14.2%. The G6PD Viangchan (871 G>A) was the most common (83.3%), followed by G6PD Mahidol (487G>A) (11.9%), and G6PD Union (1360 C>T) (4.8%). There were two cases of G6PD deficiency carrying the double mutations of Viangchan (871G > A)-Mahidol (487G > A) and Viangchan (871G > A)-Union (1360C > T). In comparison, the prevalence of G6PD deficiency was 6.1% by FS test and 7.1% by MR test. G6PD activity was 11 ± 2.5 IU/gHb in non-deficient females (mean ± SD), and 10.9 ± 0.6 IU/gHb in non-deficient males. The upper and lower limit cut-off points for partial and severe deficiency in adults were 5.7 IU/gHb (60% of the normal mean) and 0.95 IU/gHb (10% of the normal mean), respectively. All hemizygote, homozygote and double mutations were associated with severe enzyme deficiency (the residual enzyme activity <10% of the normal mean), whereas only 14.3% of the heterozygote mutations showed severe enzyme deficiency. Based on the cut-off value <5.7 IU/gHb, the quantitative G6PD assay diagnosed 83% of cases as G6PD-deficient. Using a cut-off number of negative cell >20% in

Vitamin D and vitamin B12 deficiencies are common in patients with midgut carcinoid (SI-NET).

PubMed

Lind, A; Wängberg, B; Ellegård, L

2016-09-01

Patients with small intestinal neuroendocrine tumours (SI-NET) often have diarrhoea from hormonal overproduction, surgery and medical treatment, leading to malabsorption of bile salts, fats, vitamin B12 and fat-souble vitamins. This could lead to malnutrition. We assessed nutritional status in 50 consecutive out patients with disseminated SI-NET, 25 patients in each cohort. The first cohort was descriptive and the second cohort supplemented with vitamin D, B12 and calcium. Vitamin D deficiency was defined as <50 nmol/l. All patients were assessed by clinical chemistry and dual-energy X-ray absorptiometry (DXA) and interviewed about weight changes, appetite, gastrointestinal disorders, sunhabits and the use of supplements. In the first cohort, 29% of the patients were severely and 17% moderately vitamin D deficient. In patients without prior substitution, 32% had subnormal vitamin B12 levels. Seventy-six percent had low bone density. In the second cohort with vitamin and mineral supplementation, none had severe vitamin D deficiency, but 28% had moderate deficiency. No patient had subnormal vitamin B12 levels. Sixty percent had low bone density. The serum levels of vitamin D and B12 were higher and parathyroid hormone (PTH) lower in the second cohort compared with the first cohort (P⩽0,022). Vitamin D and PTH were negatively correlated, r=-30, P=⩽0.036. Low serum levels of vitamin D and vitamin B12, and low bone density are common in patients with disseminated SI-NET. Supplementation of vitamin D, B12 and calcium resulted in higher serum levels of vitamins, lower PTH levels and diminished severe vitamin D deficiency and is thus recommended as standard care.

Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates.

PubMed

Miao, Jing-Kun; Chen, Qi-Xiong; Bao, Li-Ming; Huang, Yi; Zhang, Juan; Wan, Ke-Xing; Yi, Jing; Wang, Shi-Yi; Zou, Lin; Li, Ting-Yu

2013-09-23

Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assay's sensitivity to identify male and female G6PD deficiency neonates, respectively. We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012.

PubMed

Shamah-Levy, Teresa; Villalpando, Salvador; Mejía-Rodríguez, Fabiola; Cuevas-Nasu, Lucía; Gaona-Pineda, Elsa Berenice; Rangel-Baltazar, Eduardo; Zambrano-Mujica, Norma

2015-01-01

To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.

PubMed

Plewes, Katherine; Soontarawirat, Ingfar; Ghose, Aniruddha; Bancone, Germana; Kingston, Hugh W F; Herdman, M Trent; Leopold, Stije J; Ishioka, Haruhiko; Faiz, Md Abul; Anstey, Nicholas M; Day, Nicholas P J; Hossain, Md Amir; Imwong, Mallika; Dondorp, Arjen M; Woodrow, Charles J

2017-03-29

Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh. G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations. One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants. In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of

Short-Term Vitamin B-6 Restriction Does Not Affect Plasma Concentrations of Hydrogen Sulfide Biomarkers Lanthionine and Homolanthionine in Healthy Men and Women123

PubMed Central

DeRatt, Barbara N; Ralat, Maria A; Gregory, Jesse F

2016-01-01

Background: Suboptimal vitamin B-6 status is associated with increased cardiovascular disease risk, although the mechanism is unknown. The synthesis of the vasodilator hydrogen sulfide occurs through side reactions of the transsulfuration enzymes cystathionine β-synthase and cystathionine γ-lyase, with pyridoxal 5′-phosphate as a coenzyme. Two proposed hydrogen sulfide biomarkers, lanthionine and homolanthionine, are produced concurrently. Objective: To determine whether hydrogen sulfide production is reduced by vitamin B-6 deficiency, we examined the relations between plasma concentrations of lanthionine and homolanthionine, along with other components of the transsulfuration pathway (homocysteine, cystathionine, and Cys), in a secondary analysis of samples from 2 vitamin B-6 restriction studies in healthy men and women. Methods: Metabolite concentrations were measured in plasma from 23 healthy adults (12 men and 11 women) before and after 28-d controlled dietary vitamin B-6 restriction (0.37 ± 0.04 mg/d). Vitamin B-6 restriction effects on lanthionine and homolanthionine concentrations were assessed. Associations between hydrogen sulfide biomarkers, transsulfuration metabolites, and functional indicators of vitamin B-6 deficiency were analyzed by linear regression. Results: Preprandial plasma lanthionine and homolanthionine concentrations ranged from 89.0 to 372 nmol/L and 5.75 to 32.3 nmol/L, respectively, in healthy adults. Mean lanthionine and homolanthionine concentrations were not affected by vitamin B-6 restriction (P < 0.66), with marked heterogeneity of individual responses. After restriction, homolanthionine was positively associated with functional indicators of vitamin B-6 deficiency, which differed from hypothesized negative associations. Plasma lanthionine was positively correlated with the concentration of its precursor, Cys, before (R2 = 0.36; P = 0.002) and after (R2 = 0.37; P = 0.002) restriction. Likewise, homolanthionine concentration was

[Maternal and neonatal vitamin B12 deficiency detected by expanded newborn screening].

PubMed

Papp, Ferenc; Rácz, Gábor; Lénárt, István; Kóbor, Jenő; Bereczki, Csaba; Karg, Eszter; Baráth, Ákos

2017-12-01

Infant vitamin B 12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B 12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B 12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. To summarize our experiences gained by screening for vitamin B 12 deficiency. Clinical and laboratory data of vitamin B 12 -deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B 12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B 12 deficiency. We also detected an additional vitamin B 12 -deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B 12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B 12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B 12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.

Prevalence of vitamin A deficiency in children aged 6-9 years in Wukro, northern Ethiopia.

PubMed Central

Kassaye, T.; Receveur, O.; Johns, T.; Becklake, M. R.

2001-01-01

OBJECTIVE: To determine the prevalence of vitamin A deficiency in children aged 6-9 years in northern Ethiopia. METHODS: A cross-sectional study was carried out and the data were analysed for 824 (61.5%) of 1339 eligible children for whom there was complete information on biochemical vitamin A status, dietary vitamin A intake, ocular examination for xerophthalmia, and anthropometry. FINDINGS: The prevalence of xerophthalmia was 5.8%; serum retinol levels were below 0.35 mumol/l and between 0.35 and 0.70 mumol/l in 8.4% and 51.1% of the children respectively. The liver vitamin A reserve (modified relative dose response ratio > or = 0.06) was low in 41.0% of the children. CONCLUSION: The high prevalence of severe vitamin A deficiency in children aged 6-9 years indicates the need to reevaluate the practice of targeting vitamin A supplementation programmes on children under 6 years of age in areas where vitamin A deficiency is endemic. PMID:11417037

Biochemical characteristics of glucose-6-phosphate dehydrogenase variants among the Malays of Singapore with report of a new non-deficient (GdSingapore) and three deficient variants.

PubMed

Saha, N; Hong, S H; Wong, H A; Jeyaseelan, K; Tay, J S

1991-12-01

Biochemical characteristics of one non-deficient fast G6PD variant (GdSingapore) and six different deficient variants (three new, two Mahidol, one each of Indonesian and Mediterranean) were studied among the Malays of Singapore. The GdSingapore variant had normal enzyme activity (82%) and fast electrophoretic mobilities (140% in TEB buffer, 160% in phosphate and 140% in Tris-HCl buffer systems respectively). This variant is further characterized by normal Km for G6P; utilization of analogues (Gal6P, 2dG6P; dAmNADP), heat stability and pH optimum. The other six deficient G6PD variants had normal electrophoretic mobility in TEB buffer with enzyme activities ranging from 1 to 12% of GdB+. The biochemical characteristics identity them to be 2 Mahidol, 1 Indonesian and 1 Mediterranean variants and three new deficient variants.

The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects.

PubMed

Bancone, Germana; Kalnoky, Michael; Chu, Cindy S; Chowwiwat, Nongnud; Kahn, Maria; Malleret, Benoit; Wilaisrisak, Pornpimon; Rénia, Laurent; Domingo, Gonzalo J; Nosten, Francois

2017-08-29

Glucose-6-phosphate dehydrogenase (G6PD) activity is essential for redox equilibrium of red blood cells (RBCs) and, when compromised, the RBCs are more susceptible to haemolysis. 8-aminoquinolines (primaquine and tafenoquine) are used for the radical curative treatment of Plasmodium vivax malaria and can cause haemolysis in G6PD deficient subjects. Haemolytic risk is dependent on treatment dose and patient G6PD status but ultimately it correlates with the number of G6PD deficient RBCs. The G6PD spectrophotometric assay reliably identifies deficient subjects but is less reliable in heterozygous females, especially when other blood conditions are present. In this work we analysed samples with a range of G6PD phenotypes and haematologic conditions from 243 healthy volunteers of Asian or African-American heritage using both the spectrophotomeric assay and the G6PD flow-cytometric assay. Overall 18.5% of subjects (29.3% of Asian females) presented with anaemia, associated with decreased RBCs volume (MCV) and reticulocytosis; the flow-cytometric assay showed good correlation with the spectrophotometric assay (Pearson's r 0.918-0.957) and was less influenced by haemoglobin concentration, number of RBCs and number of reticulocytes. This resulted in more precise quantification of the number of G6PD deficient RBCs and presumably higher predictive power of drug induced haemolytic risk.

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

PubMed

Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

Toward reassessing data-deficient species.

PubMed

Bland, Lucie M; Bielby, Jon; Kearney, Stephen; Orme, C David L; Watson, James E M; Collen, Ben

2017-06-01

One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. © 2016 Society for Conservation Biology.

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

PubMed Central

Rizzo, Gianluca; Laganà, Antonio Simone; Rapisarda, Agnese Maria Chiara; La Ferrera, Gioacchina Maria Grazia; Buscema, Massimo; Rossetti, Paola; Nigro, Angela; Muscia, Vincenzo; Valenti, Gaetano; Sapia, Fabrizio; Sarpietro, Giuseppe; Zigarelli, Micol; Vitale, Salvatore Giovanni

2016-01-01

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism. PMID:27916823

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation.

PubMed

Rizzo, Gianluca; Laganà, Antonio Simone; Rapisarda, Agnese Maria Chiara; La Ferrera, Gioacchina Maria Grazia; Buscema, Massimo; Rossetti, Paola; Nigro, Angela; Muscia, Vincenzo; Valenti, Gaetano; Sapia, Fabrizio; Sarpietro, Giuseppe; Zigarelli, Micol; Vitale, Salvatore Giovanni

2016-11-29

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

A new paper-based analytical device for detection of Glucose-6-phosphate dehydrogenase deficiency.

PubMed

Kaewarsa, Phuritat; Laiwattanapaisal, Wanida; Palasuwan, Attakorn; Palasuwan, Duangdao

2017-03-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic haemolytic disorder. Most persons with G6PD deficiency are asymptomatic, but exposure to oxidant drugs, such as the anti-malarial drug primaquine, may induce haemolysis, which is commonly found in Asian countries. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis. This study proposes a novel quantitative method to detect G6PD deficiency using paper-based analytical devices (G6PDD-PAD). Wax printing was utilized for fabricating circular reaction zone patterns in paper. The colorimetric assay is based on the formation of formazan via a reduction of tetra-nitro blue tetrazolium (TNBT) by the G6PD enzyme on G6PDD-PAD. Detection was achieved by capturing the colour using a desktop scanner and the colour intensity was analysed with Adobe Photoshop C56. The results showed that the G6PD activity analysed by G6PDD-PAD was highly correlated with the standard biochemical assay (SBA) (r 2 =0.87, p<0.01). Moreover, good agreement by Bland-Altman bias plot was demonstrated between G6PDD-PAD and the SBA (mean bias 1.4 IU/gHb). The detection limit was 0 IU/gHb of G6PD activity. This study demonstrates the feasibility of using G6PDD-PAD. This simple, low-cost test ($0.1/test) should be useful for diagnosing G6PD deficiency in resource-limited settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Glucose-6-phosphate dehydrogenase deficiency in Tunisia: molecular data and phenotype-genotype association.

PubMed

Laouini, N; Bibi, A; Ammar, H; Kazdaghli, K; Ouali, F; Othmani, R; Amdouni, S; Haloui, S; Sahli, C A; Jouini, L; Hadj Fredj, S; Siala, H; Ben Romdhane, N; Toumi, N E; Fattoum, S; Messsaoud, T

2013-02-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. In this study, we aimed to perform a molecular investigation of G6PD deficiency in Tunisia and to associate clinical manifestations and the degree of deficiency with the genotype. A total of 161 Tunisian subjects of both sexes were screened by spectrophotometric assay for enzyme activity. Out of these, 54 unrelated subjects were selected for screening of the most frequent mutations in Tunisia by PCR/RFLP, followed by size-based separation of double-stranded fragments under non-denaturing conditions on a denaturing high performance liquid chromatography system. Of the 56 altered chromosomes examined, 75 % had the GdA(-) mutation, 14.28 % showed the GdB(-) mutation and no mutations were identified in 10.72 % of cases. Hemizygous males with GdA(-) mutation were mostly of class III, while those with GdB(-) mutation were mainly of class II. The principal clinical manifestation encountered was favism. Acute hemolytic crises induced by drugs or infections and neonatal jaundice were also noted. Less severe clinical features such as low back pain were present in heterozygous females and in one homozygous female. Asymptomatic individuals were in majority heterozygote females and strangely one hemizygous male. The spectrum of mutations seems to be homogeneous and similar to that of Mediterranean countries; nevertheless 10.72 % of cases remain with undetermined mutation thus suggesting a potential heterogeneity of the deficiency at the molecular level. On the other hand, we note a better association of the molecular defects with the severity of the deficiency than with clinical manifestations.

OCT Angiographic Findings in Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Jiang, Shangjun; Choudhry, Netan

2017-08-01

Fovea plana (FP) describes the abnormal absence of the foveal pit in the retina. It is a sign that is associated with prematurity, albinism, and other ophthalmic disorders. The authors present the optical coherence tomography angiographic findings in a case of a 19-year-old male with FP and glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is a very common condition that typically presents with hemolytic anemia and jaundice. G6PD deficiency is also known to affect vision, but these pathologies have been less well-characterized. To the authors' knowledge, this is the first report of G6PD deficiency in FP. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:664-667.]. Copyright 2017, SLACK Incorporated.

Fulminant hemolysis in glucose-6-phosphate dehydrogenase deficiency.

PubMed

Moiz, Bushra; Ali, Sidra Asad

2018-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder affecting some 400 million people worldwide. Though clinically silent, it may result in hemolysis on oxidative stress induced by drugs or infections. Viral hepatitis A with coexisting G6PD deficiency can be devastating associated with severe hemolysis, anemia, renal failure, and hepatic encephalopathy.

Vitamin Status among Breastfed Infants in Bhaktapur, Nepal

PubMed Central

Ulak, Manjeswori; Chandyo, Ram K.; Thorne-Lyman, Andrew L.; Henjum, Sigrun; Ueland, Per M.; Midttun, Øivind; Shrestha, Prakash S.; Fawzi, Wafaie W.; Graybill, Lauren; Strand, Tor A.

2016-01-01

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B6, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5′-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B6 deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal. PMID:27005657

Molecular characterization of G6PD deficiency in Cyprus.

PubMed

Drousiotou, Anthi; Touma, Elias H; Andreou, Nicoletta; Loiselet, Jacques; Angastiniotis, Michalis; Verrelli, Brian C; Tishkoff, Sarah A

2004-01-01

In the present study, we determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus using two different procedures in two separate adult population groups: a semiquantitative fluorescence test on blood spotted on filter paper and a quantitative spectrophotometric test on liquid blood. The frequency of G6PD deficiency among healthy adult males was found to be 5.1% using the semiquantitative procedure and 6.4% using the quantitative procedure. Neither method was able to detect all the expected female heterozygotes (5.3% and 47.1% of the expected number, respectively). A total of 21 male hemizygotes, 1 female homozygote and 9 female heterozygotes that tested positive for G6PD deficiency were studied at the molecular level. All 32 chromosomes were genotyped and five different mutations were identified. The Mediterranean mutation in exon 6 (563C-->T) (Ser188Phe) was found to be the most common variant in the Cypriot population, accounting for 52.6% of the deficient alleles. In the remaining chromosomes, four different mutations were identified: three known mutations, Kaiping 1388G-->A (Arg463His), Chatham 1003G-->A (Ala335Thr) and Acrokorinthos 463C-->G (His155Asp), and one previously undescribed mutation in exon 3, 148C-->T (Pro50Ser), which we called G6PD Kambos. We conclude that the frequency of G6PD deficiency in Cypriot males is 6.4%, and that this deficiency is the result of several different mutations. Although all the individuals carrying the Mediterranean variant can be detected using a semiquantitative screening method, a quantitative enzyme measurement is required to detect the G6PD variants with less severe enzyme deficiencies, while the most appropriate method for heterozygote detection is DNA analysis.

Effect of supplementation with a lipid-based nutrient supplement on the micronutrient status of children aged 6-18 months living in the rural region of Intibucá, Honduras.

PubMed

Siega-Riz, Anna M; Estrada Del Campo, Yaniré; Kinlaw, Alan; Reinhart, Gregory A; Allen, Lindsay H; Shahab-Ferdows, Setareh; Heck, Jeff; Suchindran, Chirayath M; Bentley, Margaret E

2014-05-01

Lipid-based nutrient supplements (LNS) have been effective in the treatment of acute malnutrition among children. We evaluated the use of LNS supplementation for improving the micronutrient status of young children. A 12-month randomised controlled trial was conducted among children aged 6-18 months living in Intibucá, Honduras. Communities (n = 18) were randomised into clusters matched by poverty indicators (9 intervention, n = 160 and 9 controls, n = 140). Intervention participants received LNS. All children received food vouchers and nutrition education. Primary outcomes included measures of micronutrient status: at baseline, 6 and 12 months' blood were collected for assessment of folate, iron, zinc, riboflavin, and vitamin B12 status; haemoglobin was measured every 3 months; and dietary and anthropometry collected monthly. Longitudinal analyses were based on intent to treat and LNS adherence. Generalised estimating equations were used in the estimation of generalised linear regression models specified for the data. At 6-month follow-up, children in the intervention group had a lower proportion classified as deficient for B12 (43.6%) compared with the control (67.7%; P = 0.03). The intervention group had a higher mean concentration for folate at 6 months (P = 0.06), and improvements continued through 12 months for folate (P = 0.002) and vitamin A deficiency (P = 0.03). This pattern of results, with improved significance, remained in subanalysis based on LNS adherence. These data demonstrate that LNS improved select micronutrient status in young non-malnourished Honduran children. © 2014 John Wiley & Sons Ltd.

SIRT6 deficiency culminates in low-turnover osteopenia.

PubMed

Sugatani, Toshifumi; Agapova, Olga; Malluche, Hartmut H; Hruska, Keith A

2015-12-01

Deficiency of Sirtuin 6 (SIRT6), a chromatin-related deacetylase, in mice reveals severe premature aging phenotypes including osteopenia. However, the underlying molecular mechanisms of SIRT6 in bone metabolism are unknown. Here we show that SIRT6 deficiency in mice produces low-turnover osteopenia caused by impaired bone formation and bone resorption, which are mechanisms similar to those of age-related bone loss. Mechanistically, SIRT6 interacts with runt-related transcription factor 2 (Runx2) and osterix (Osx), which are the two key transcriptional regulators of osteoblastogenesis, and deacetylates histone H3 at Lysine 9 (H3K9) at their promoters. Hence, excessively elevated Runx2 and Osx in SIRT6(-/-) osteoblasts lead to impaired osteoblastogenesis. In addition, SIRT6 deficiency produces hyperacetylation of H3K9 in the promoter of dickkopf-related protein 1 (Dkk1), a potent negative regulator of osteoblastogenesis, and osteoprotegerin, an inhibitor of osteoclastogenesis. Therefore, the resulting up-regulation of Dkk1 and osteoprotegerin levels contribute to impaired bone remodeling, leading to osteopenia with a low bone turnover in SIRT6-deficient mice. These results establish a new link between SIRT6 and bone remodeling that positively regulates osteoblastogenesis and osteoclastogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of age, period and birth-cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults.

PubMed

Pes, Giovanni Mario; Errigo, Alessandra; Bitti, Angela; Dore, Maria Pina

2018-02-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD-deficiency across age groups and birth cohorts was investigated using Age-Period-Cohort analysis. Data were collected from the clinical records of 11,252 patients (6975 women, age range 17-94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency. Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age-Period-Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively). These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues. Key message The frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication.

[Vitamin B12 deficiency associated with high doses od metformin in older people diabetic].

PubMed

Sánchez, Hugo; Masferrer, Dominique; Lera, Lydia; Arancibia, Estrella; Angel, Barbara; Albala, Cecilia

2014-06-01

The aim of the study was to estimate if B12 deficiency is associated with the use of metformin in the elderly diabetics. Case-control study in diabetic OP. Cases (n = 137) were defined as elderly with B12 < 221 pmol/L and controls (n = 279) elderly with B12 > 221 pmol/L. Four categories of metformin use were defined: non-users, ≤850 mg/day, > 850 and < 2,550 mg/day and ≥2,550 mg/day. Metformin ≥2,550 mg/day was high doses considered. The crude OR for B12 deficiency and consumption of Metformin were calculated. Logistic regression models were developed to explore the association between B12 deficiency and metformin dose. The research protocol was approved by the Ethics Committee of INTA. The age of cases and controls was (70.2 years vs 68.6 years (p < 0.05). The 62% were women in cases vs 74.9% in controls (p < 0.05). The 73% of cases and 76% of controls used metformin (p < 0.05) the average consumption of metformin was de 1,954.3 mg/day (SD: 1,063.2) in cases and 1,696.6 mg/day (SD: 1,074.4) in controls (p < 0.05). The use of 2,550 mg/day was observed in 29.2% of cases and 19.3% for controls (p < 0.05). It was observed that OP who consumed high doses of metformin had 1.9 times the risk of B12 deficiency (OR: 1.9; 95%CI: 1,08- 3,30). These results show a strong association between high doses of metformin and low levels of vitamin B12 in diabetic elderly. This project was funded by FONIS SA11I2092. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in African children with severe malaria.

PubMed

Nguetse, Christian N; Meyer, Christian G; Adegnika, Ayola Akim; Agbenyega, Tsiri; Ogutu, Bernhards R; Kremsner, Peter G; Velavan, Thirumalaisamy P

2016-07-07

Extensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti-malarial drug induced with haemolytic anaemia. A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6-120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A(+)) and deficient (type A(-)) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia. Two hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia. In this study, moderately (type A(+)) and severely (type A(-)) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission.

Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

PubMed

Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

2017-08-01

Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.

PubMed

Guindo, Aldiouma; Fairhurst, Rick M; Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

2007-03-01

Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A- form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. We conducted large case-control studies of the A- form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. The A- form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these

X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

PubMed Central

Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

2007-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A− form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. Methods and Findings We conducted large case-control studies of the A− form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. Conclusions The A− form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is

High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.

PubMed

Fanello, Caterina I; Karema, Corine; Avellino, Pamela; Bancone, Germana; Uwimana, Aline; Lee, Sue J; d'Alessandro, Umberto; Modiano, David

2008-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7). CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary.

Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial.

PubMed

Torsvik, Ingrid Kristin; Ueland, Per Magne; Markestad, Trond; Midttun, Øivind; Bjørke Monsen, Anne-Lise

2015-12-18

Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months. Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month. Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03). The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function

Anemia and Micronutrient Status of Women of Childbearing Age and Children 6-59 Months in the Democratic Republic of the Congo.

PubMed

Harvey-Leeson, Sarah; Karakochuk, Crystal D; Hawes, Meaghan; Tugirimana, Pierrot L; Bahizire, Esto; Akilimali, Pierre Z; Michaux, Kristina D; Lynd, Larry D; Whitfield, Kyly C; Moursi, Mourad; Boy, Erick; Foley, Jennifer; McLean, Judy; Houghton, Lisa A; Gibson, Rosalind S; Green, Tim J

2016-02-17

Little is known about the micronutrient status of women and children in the Democratic Republic of the Congo, which is critical for the design of effective nutrition interventions. We recruited 744 mother-child pairs from South Kivu (SK) and Kongo Central (KC). We determined hemoglobin (Hb), serum zinc, vitamin B12, folate, ferritin, soluble transferrin receptor (sTfR), retinol binding protein (RBP), C-reactive protein, and α-1 acid glycoprotein concentrations. Anemia prevalence was determined using Hb adjusted for altitude alone and Hb adjusted for both altitude and ethnicity. Anemia prevalence was lower after Hb adjustment for altitude and ethnicity, compared to only altitude, among women (6% vs. 17% in SK; 10% vs. 32% in KC), children 6-23 months (26% vs. 59% in SK; 25% vs. 42% in KC), and children 24-59 months (14% vs. 35% in SK; 23% vs. 44% in KC), respectively. Iron deficiency was seemingly higher with sTfR as compared to inflammation-adjusted ferritin among women (18% vs. 4% in SK; 21% vs. 5% in KC), children 6-23 months (51% vs. 14% in SK; 74% vs. 10% in KC), and children 24-59 months (23% vs. 4% in SK; 58% vs. 1% in KC). Regardless of indicator, iron deficiency anemia (IDA) never exceeded 3% in women. In children, IDA reached almost 20% when sTfR was used but was only 10% with ferritin. Folate, B12, and vitamin A (RBP) deficiencies were all very low (<5%); RBP was 10% in children. The prevalence of anemia was unexpectedly low. Inflammation-adjusted zinc deficiency was high among women (52% in SK; 58% in KC), children 6-23 months (23% in SK; 20% in KC), and children 24-59 months (25% in SK; 27% in KC). The rate of biochemical zinc deficiency among Congolese women and children requires attention.

Msh6 Protects Mature B Cells from Lymphoma by Preserving Genomic Stability

PubMed Central

Peled, Jonathan U.; Sellers, Rani S.; Iglesias-Ussel, Maria D.; Shin, Dong-Mi; Montagna, Cristina; Zhao, Chunfang; Li, Ziqiang; Edelmann, Winfried; Morse, Herbert C.; Scharff, Matthew D.

2010-01-01

Most human B-cell non-Hodgkin’s lymphomas arise from germinal centers. Within these sites, the mismatch repair factor MSH6 participates in antibody diversification. Reminiscent of the neoplasms arising in patients with Lynch syndrome III, mice deficient in MSH6 die prematurely of lymphoma. In this study, we characterized the B-cell tumors in MSH6-deficient mice and describe their histological, immunohistochemical, and molecular features, which include moderate microsatellite instability. Based on histological markers and gene expression, the tumor cells seem to be at or beyond the germinal center stage. The simultaneous loss of MSH6 and of activation-induced cytidine deaminase did not appreciably affect the survival of these animals, suggesting that these germinal center-like tumors arose by an activation-induced cytidine deaminase-independent pathway. We conclude that MSH6 protects B cells from neoplastic transformation by preserving genomic stability. PMID:20934970

Glucose-6-Phosphate Dehydrogenase-Deficiency in Transfusion Medicine: The Unknown Risks

PubMed Central

Francis, Richard O.; Jhang, Jeffrey S.; Pham, Huy P.; Hod, Eldad A.; Zimring, James C.; Spitalnik, Steven L.

2013-01-01

The hallmark of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce hemolysis in G6PD-deficient RBCs. Although it is not routine practice to screen healthy blood donors for G6PD deficiency, case reports identified transfusion of G6PD-deficient RBCs as causing hemolysis and other adverse events. In addition, some patient populations may be more at risk for complications associated with transfusions of G6PD-deficient RBCs because they receive RBCs from donors who are more likely to have G6PD deficiency. This review discusses G6PD deficiency, its importance in transfusion medicine, changes in the RBC antioxidant system (of which G6PD is essential) during refrigerated storage, and mechanisms of hemolysis. In addition, as yet unanswered questions that could be addressed by translational and clinical studies are identified and discussed. PMID:23815264

Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks.

PubMed

Francis, R O; Jhang, J S; Pham, H P; Hod, E A; Zimring, J C; Spitalnik, S L

2013-11-01

The hallmark of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce haemolysis in G6PD-deficient RBCs. Although it is not routine practice to screen healthy blood donors for G6PD deficiency, case reports identified transfusion of G6PD-deficient RBCs as causing haemolysis and other adverse events. In addition, some patient populations may be more at risk for complications associated with transfusions of G6PD-deficient RBCs because they receive RBCs from donors who are more likely to have G6PD deficiency. This review discusses G6PD deficiency, its importance in transfusion medicine, changes in the RBC antioxidant system (of which G6PD is essential) during refrigerated storage and mechanisms of haemolysis. In addition, as yet unanswered questions that could be addressed by translational and clinical studies are identified and discussed. © 2013 International Society of Blood Transfusion.

Erythrocyte glucose-6-phosphate dehydrogenase (1.1.1.49) deficiency in Antalya province, Turkey: an epidemiologic and biochemical study.

PubMed

Aksu, T A; Esen, F; Dolunay, M S; Alicigüzel, Y; Yücel, G; Cali, S; Baykal, Y

1990-06-01

Glucose-6-phosphate dehydrogenase (1.1.1.49) activity was assessed in 1986-1988 in blood samples from 1,521 individuals from 375 families living an Antalya city and adjacent villages by Beutler's fluorescence spot test. The families were randomly selected by the State Statistical Institute. Complete deficiency occurred in 7.4% of males and 1.8% of females. Mean enzyme activity was 6.77 +/- 1.07 IU/g Hb in normals and ranged between 0 and 0.48 IU/g Hb in those considered deficient. Kinetic measurements made with partially purified enzyme showed that GdB+ and GdB- variants were present in normal and in deficient subjects, respectively.

Glucose-6-phosphate dehydrogenase deficiency in Singapore.

PubMed

Quak, S H; Saha, N; Tay, J S

1996-01-01

Glucose-6-phosphate dehydrogenase (G6PD) in man is an X-linked enzyme. The deficiency of this enzyme is one of the most common inherited metabolic disorders in man. In Singapore, three clinical syndromes associated with G6PD deficiency had been described: severe haemolysis in neonates with kernicterus, haemoglobinuria and "viral hepatitis"-like syndrome. The human G6PD monomer consists of 515 amino acids. Only the tetrameric or dimeric forms composed of a single type subunit are catylitically active. The complete amino acid sequence of G6PD had been elucidated in man and various other animals. The region of high homology among the enzymes of various animals is presumably functionally active. Among the Chinese in Singapore, three common molecular variants had been identified: Canton (nt 1376 G --> T), Kaiping (nt 1388 G --> A) and Mediterranean (nt 563 C --> T) in frequencies of 24%, 21% and 10% respectively. In addition, two common mutants (Gaozhou, nt 95 A --> G and Chinese 5, nt 1024 C --> T) have been detected in Singapore Chinese in low frequencies. In Malays, 6 different deficient variants are known in Singapore (3 new, 1 Mahidol, 1 Indonesian and 1 Mediterranean).

Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates.

PubMed

M Abo El Fotoh, Wafaa Moustafa; Rizk, Mohammed Soliman

2016-12-01

The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia. To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer's instructions. A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases. Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

[Maternal vitamin B12 deficiency: cause for neurological symptoms in infancy].

PubMed

Lücke, T; Korenke, G C; Poggenburg, I; Bentele, K H P; Das, A M; Hartmann, H

2007-08-01

Symptoms of Vitamin B (12) deficiency in infancy include growth retardation, regression of psychomotor development, muscular hypotonia and brain atrophy. Besides an inappropriate vegetarian diet of the infants, a vegan diet or a pernicious anaemia of the mother may lead to an insufficient vitamin B (12) supply of the child. We report here the neurological symptoms of 4 fully breast-fed infants from mothers on vegan diet or with pernicious anaemia. Vitamin B (12) deficiency can easily be diagnosed by detection of methylmalonic acid when measuring the organic acids in urine. Vitamin B (12) deficiency should be avoided or diagnosed as early as possible since a supplementation of mother and child can prevent neurological symptoms of the baby. Furthermore, the neurological symptoms of the infant with manifest vitamin B (12) deficiency are (partially) reversible.

Pyridoxine deficiency in adult patients with status epilepticus.

PubMed

Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

2015-11-01

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.

PubMed

Larson, Austin A; Balasubramaniam, Shanti; Christodoulou, John; Burrage, Lindsay C; Marom, Ronit; Graham, Brett H; Diaz, George A; Glamuzina, Emma; Hauser, Natalie; Heese, Bryce; Horvath, Gabriella; Mattman, Andre; van Karnebeek, Clara; Lane Rutledge, S; Williamson, Amy; Estrella, Lissette; Van Hove, Johan K L; Weisfeld-Adams, James D

2018-01-04

Elevations of specific acylcarnitines in blood reflect carboxylase deficiencies, and have utility in newborn screening for life-threatening organic acidemias and other inherited metabolic diseases. In this report, we describe a newly-identified association of biochemical features of multiple carboxylase deficiency in individuals harboring mitochondrial DNA (mtDNA) mutations in MT-ATP6 and in whom organic acidemias and multiple carboxylase deficiencies were excluded. Using retrospective chart review, we identified eleven individuals with abnormally elevated propionylcarnitine (C3) or hydroxyisovalerylcarnitine (C5OH) with mutations in MT-ATP6, most commonly m.8993T>G in high heteroplasmy or homoplasmy. Most patients were ascertained on newborn screening; most had normal enzymatic or molecular genetic testing to exclude biotinidase and holocarboxylase synthetase deficiencies. MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up. These cases expand the biochemical phenotype associated with MT-ATP6 mutations, especially m.8993T>G, to include acylcarnitine abnormalities mimicking carboxylase deficiency states. Clinicians should be aware of this association and its implications for newborn screening, and consider mtDNA sequencing in patients exhibiting similar acylcarnitine abnormalities that are biotin-unresponsive and in whom other enzymatic deficiencies have been excluded. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Anaemia, folate and vitamin B12 deficiency among pregnant women in an area of unstable malaria transmission in eastern Sudan.

PubMed

Abdelrahim, Ishraga I; Adam, Gamal K; Mohmmed, Ahmed A; Salih, Magdi M; Ali, Naji I; Elbashier, Mustafa I; Adam, Ishag

2009-05-01

A cross-sectional study was carried out between October 2007 and January 2008 to investigate the prevalence and types of anaemia among pregnant women of eastern Sudan. Socio-demographic and obstetrical data were collected using a questionnaire. Haemoglobin (Hb), serum ferritin, serum folate and vitamin B(12) were assessed using standard laboratory methods. Two hundred and seventy-nine pregnant Sudanese women were recruited. Anaemia (Hb <11 gdl) and iron deficiency (ferritin <15 microg/l) were prevalent in 80.3 and 14.3% of the study sample, respectively. Of the total sample, 11.1% had iron-deficiency anaemia. Serum folate (<6.6 ng/ml) and vitamin B(12) (<150 pg/ml) deficiency was reported in 57.7 and 1%, respectively, and none of the women had both folate and vitamin B(12) deficiencies. Univariate and multivariate analyses showed that ferritin, serum folate and vitamin B(12) levels were not significantly associated with anaemia. Thus, there was a high prevalence of anaemia and folate deficiency. Measures to control these should be considered.

Prevalence, genetic variants and clinical implications of G-6-PD deficiency in Burkina Faso: a systematic review.

PubMed

Ouattara, Abdoul Karim; Yameogo, Pouiré; Traore, Lassina; Diarra, Birama; Assih, Maléki; Compaore, Tegwindé Rébéca; Obiri-Yeboah, Dorcas; Soubeiga, Serge Théophile; Djigma, Florencia Wendkuuni; Simpore, Jacques

2017-11-23

It is now well-known that some antimalarials such as primaquine may induce severe hemolytic anemia in people with G-6-PD deficiency. Antimalarial drug prescriptions must, therefore take into account the patient's G-6-PD status in malaria endemic areas such as Burkina Faso, where the prevalence of this genetic abnormality is relatively high. Although great clinical heterogeneity is observed depending on the molecular nature of the deficiency and the residual enzyme activity in the red blood cell, there is very poor data on the prevalence of G-6-PD deficiency and the distribution of involved genetic variants in Burkina Faso. In this systematic review, we present a synthesis of the various studies carried out on the G-6-PD deficiency in Burkina Faso in order to determine its prevalence, probable distribution of the genetic variants involved and their clinical implications for a national systematic screening policy among the groups most vulnerable to malaria. A systematic review was carried out to analyze available published data on the prevalence, phenotypes and mutations responsible for G-6-PD deficiency in Burkina Faso. The key words used were "G-6-PD deficiency AND Burkina Faso" or "Déficit en G-6-PD AND Burkina Faso" in French. To identify the relevant articles, two independent reviewers reviewed the titles, abstracts and the full text of the selected papers. An average prevalence of 16.6% (183/1100; CI 95%: 0.145-0.190) and 6.5% (69/1066; CI 95%: 0.051-0.081) of G-6-PD deficiency was found respectively in men and women in this systematic review. Although the predominance (99.8% of G-6-PD deficient cases) of 202A/376G G-6-PD A- variant, the Santamaria and Betica Selma variants were identified in Burkina Faso. Independently of the method used, the enzymatic deficiency was significantly higher in males (2.5-20.5%) compared to females (3.3-12.3%). This systematic review suggests that despite the ubiquity of the 202A/376G G-6-PD A- variant in Burkina Faso, it will be

Effect of micronutrient supplement on health and nutritional status of schoolchildren: biochemical status.

PubMed

Sivakumar, Battiprolu; Nair, Krishnapillai Madhavan; Sreeramulu, Dande; Suryanarayana, Palla; Ravinder, Punjal; Shatrugna, Veena; Kumar, Prattipati Ajey; Raghunath, Manchala; Rao, Varaganti Vikas; Balakrishna, Nagalla; Kumar, Putcha Uday; Raghuramulu, Namala

2006-01-01

We assessed the effect of a daily intake of a micronutrient-fortified beverage for 14 mo on indicators of biochemical status of important micronutrients in schoolchildren. A double-blind, placebo-controlled, matched-pair, cluster, randomization study design was used. Biochemical indicators of micronutrient status were evaluated at baseline and at the end of 14 mo on a subsample in nine matched pairs. Prevalence (percentage) of subclinical deficiency, mean, and mean increments of each indicator were compared between supplemented and placebo groups. Extent of inadequacy at baseline was more or less 100% for folic acid, 65% for vitamins B2 and B6, and 55% for vitamins C and A. Prevalence of anemia among subjects was 55%, with inadequacy of vitamin B12 being 40% and that of vitamin D being 30%. No subject had inadequacy of iodine based on urinary iodine. Supplementation of a micronutrient-enriched beverage for 14 mo significantly improved the status of many of the nutrients. The effect was significant with respect to vitamins A, B2, and B12, folic acid, vitamin D, parathyroid hormone, and thyroid-stimulating hormone in children who received the supplement compared with those who received only placebo. Hemoglobin status improved only in children who had anemia in the supplemented group. Prevalence of multiple subclinical micronutrient deficiencies are high in middle-income Indian school children. Daily consumption of a micronutrient-enriched beverage had positive effects that were confined to those nutrients that were inadequate at baseline.

The influence of vitamin A status on iron-deficiency anaemia in anaemic adolescent schoolgirls in Myanmar.

PubMed

Htet, Min Kyaw; Fahmida, Umi; Dillon, Drupadi; Akib, Arwin; Utomo, Budi; Thurnham, David I

2014-10-01

The present study was conducted to investigate reasons for the high prevalence of anaemia among adolescent schoolgirls and to elucidate the role of vitamin A in contributing to Fe-deficiency anaemia (IDA). Among 1269 schoolgirls who were previously screened for anaemia (Hb < 120 g/l), 391 anaemic girls were further assessed for Fe, vitamin A and subclinical inflammation status. Fe and vitamin A indicators were corrected for inflammation and were compared in the Fe-deficient and non-deficient groups as well as between those with and without inflammation. Logistic regression was done to determine whether vitamin A status and subclinical inflammation were risk factors for Fe deficiency. The differences in Fe status among tertiles of vitamin A concentrations were assessed using ANOVA. Myanmar. Adolescent schoolgirls (n 391). One-third of the anaemia (30·4%) was IDA. Prevalence of low vitamin A status (serum retinol <1·05 μmol/l) was 31·5%. Fe and vitamin A status were significantly different between the IDA and non-IDA groups and also based on their inflammation status. Logistic regression showed that low vitamin A status was a significant predictor for being Fe deficient (OR = 1·81; 95% CI 1·03, 3·19 and OR = 2·31; 1·31, 4·07 in the middle (1·056-1·298 μmol/l) and low (≤1·056 μmol/l) vitamin A tertiles, respectively). ANOVA showed that better Fe status was associated with a higher concentration of serum retinol but only in IDA. Fe deficiency was not the main cause of anaemia in the present population. The role of vitamin A as well as other micronutrients should be taken into account in addressing the problem of anaemia.

Cardiolipin deficiency causes a dissociation of the b 6 c:caa 3 megacomplex in B. subtilis membranes.

PubMed

García Montes de Oca, Led Yered Jafet; Cabellos Avelar, Tecilli; Picón Garrido, Gerardo Ignacio; Chagoya-López, Alicia; González de la Vara, Luis; Delgado Buenrostro, Norma Laura; Chirino-López, Yolanda Irasema; Gómez-Lojero, Carlos; Gutiérrez-Cirlos, Emma Berta

2016-08-01

The associations among respiratory complexes in energy-transducing membranes have been established. In fact, it is known that the Gram-negative bacteria Paracoccus denitrificans and Escherichia coli have respiratory supercomplexes in their membranes. These supercomplexes are important for channeling substrates between enzymes in a metabolic pathway, and the assembly of these supercomplexes depends on the protein subunits and membrane lipids, mainly cardiolipin, which is present in both the mitochondrial inner membrane and bacterial membranes. The Gram-positive bacterium Bacillus subtilis has a branched respiratory chain, in which some complexes generate proton motive force whereas others constitute an escape valve of excess reducing power. Some peculiarities of this respiratory chain are the following: a type II NADH dehydrogenase, a unique b 6 c complex that has a b 6 type cytochrome with a covalently bound heme, and a c-type heme attached to the third subunit, which is similar to subunit IV of the photosynthetic b 6 f complex. Cytochrome c oxygen reductase (caa 3 ) contains a c-type cytochrome on subunit I. We previously showed that the b 6 c and the caa 3 complexes form a supercomplex. Both the b 6 c and the caa 3 together with the quinol oxygen reductase aa 3 generate the proton motive force in B. subtilis. In order to seek proof that this supercomplex is important for bacterial growth in aerobic conditions we compared the b 6 c: caa 3 supercomplex from wild type membranes with membranes from two mutants lacking cardiolipin. Both mutant complexes were found to have similar activity and heme content as the wild type. Clear native electrophoresis showed that mutants lacking cardiolipin had b 6 c:caa 3 supercomplexes of lower mass or even individual complexes after membrane solubilization with digitonin. The use of dodecyl maltoside revealed a more evident difference between wild-type and mutant supercomplexes. Here we provide evidence showing that cardiolipin

Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significa...

Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials

PubMed Central

2011-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Methods Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Results Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or

Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials.

PubMed

Carter, Nick; Pamba, Allan; Duparc, Stephan; Waitumbi, John N

2011-08-17

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline

26 CFR 1.963-6 - Deficiency distribution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAXES Controlled Foreign Corporations § 1.963-6 Deficiency distribution. (a) In general... the election under section 963 applied, but only if the subsequent deficiency distribution meets the... to which such election relates does not apply for such taxable year because of the failure of such...

Maternal folate status, but not that of vitamins B-12 or B-6, is associated with gestational age and preterm birth risk in a multiethnic Asian population.

PubMed

Chen, Ling-Wei; Lim, Ai Lin; Colega, Marjorelee; Tint, Mya-Thway; Aris, Izzuddin M; Tan, Chuen Seng; Chong, Yap-Seng; Gluckman, Peter D; Godfrey, Keith M; Kwek, Kenneth; Saw, Seang-Mei; Yap, Fabian; Lee, Yung Seng; Chong, Mary Foong-Fong; van Dam, Rob M

2015-01-01

Maternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive. We aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore. Maternal blood samples (n = 999) collected during weeks 26-28 of gestation were assayed for plasma folate, vitamin B-12, and vitamin B-6 concentrations. Birth weight and gestational age data were obtained from hospital records, and other anthropometric variables were measured within 72 h after birth. Relations between B-vitamin status and birth outcomes were assessed by linear or logistic regression with adjustment for potential confounders. Median (IQR) plasma concentrations were 34.4 (24.5-44.6) nmol/L for folate, 209 (167-258) pmol/L for vitamin B-12, and 61.8 (25.9-113) nmol/L for vitamin B-6. We found that higher plasma folate concentrations were associated with a longer gestational age (0.12 wk per SD increase in folate; 95% CI: 0.02, 0.21) and tended to be associated with lower risk of all preterm birth (delivery at <37 wk of gestation; OR: 0.79; 95% CI: 0.63, 1.00) and spontaneous preterm birth (OR: 0.76; 95% CI: 0.56, 1.04). Overall, concentrations of maternal folate, vitamin B-12, and vitamin B-6 were not independently associated with birth weight or being born small for gestational age (SGA; birth weight <10th percentile for gestational age). Higher maternal folate concentrations during late pregnancy were associated with longer gestational age and tended to be associated with a lower risk of preterm birth in this multiethnic Asian population. In contrast, the results of our study suggested little or no benefit of higher folate concentrations for reducing the risk of SGA or of higher vitamin B-6 and vitamin B-12 concentrations for reducing the risk of preterm birth or SGA. © 2015 American Society for Nutrition.

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets.

PubMed

Hecker, Peter A; Mapanga, Rudo F; Kimar, Charlene P; Ribeiro, Rogerio F; Brown, Bethany H; O'Connell, Kelly A; Cox, James W; Shekar, Kadambari C; Asemu, Girma; Essop, M Faadiel; Stanley, William C

2012-10-15

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects.

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

PubMed Central

Hecker, Peter A.; Mapanga, Rudo F.; Kimar, Charlene P.; Ribeiro, Rogerio F.; Brown, Bethany H.; O'Connell, Kelly A.; Cox, James W.; Shekar, Kadambari C.; Asemu, Girma; Essop, M. Faadiel

2012-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects. PMID:22829586

Hematological parameters and red blood cell morphological abnormality of Glucose-6-Phosphate dehydrogenase deficiency co-inherited with thalassemia.

PubMed

Pengon, Jutharat; Svasti, Saovaros; Kamchonwongpaisan, Sumalee; Vattanaviboon, Phantip

2018-03-01

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and thalassemia are genetically independent hemolytic disorders. Co-inheritance of both disorders may affect red blood cell pathology to a greater extent than normally seen in either disorder alone. This study determines the prevalence and evaluates hematological changes of G-6-PD deficiency and thalassemia co-inheritance. G-6-PD deficiency was screened from 200 male thalassemia blood samples using a fluorescent spot test. Hematological parameters and red blood cell morphology were evaluated among G-6-PD deficiency/thalassemia co-inheritance, G-6-PD deficiency alone, thalassemia alone, and normal individuals. G-6-PD deficiency was detected together with hemoglobin (Hb) E heterozygote, Hb E homozygote, β-thalassemia trait, and β-thalassemia/Hb E, α-thalassemia-2 trait, and Hb H disease. Hb level, hematocrit, mean cell volume, and mean cell Hb of G-6-PD deficiency co-inherited with asymptomatic thalassemia carriers show significantly lower mean values compared to carriers with only the same thalassemia genotypes. Higher mean red blood cell distribution width was observed in G-6-PD deficiency co-inherited with Hb E heterozygote, as with numbers of hemighost cells in G-6-PD deficiency/thalassemia co-inheritance compared to those with either disorder. Apart from Hb level, hematological parameters of co-inheritance disorders were not different from individuals with a single thalassemia disease. G-6-PD deficiency co-inherited with thalassemia in males was present in 10% of the participants, resulting in worsening of red blood cell pathology compared with inheritance of thalassemia alone. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

CD22 x Siglec-G double-deficient mice have massively increased B1 cell numbers and develop systemic autoimmunity.

PubMed

Jellusova, Julia; Wellmann, Ute; Amann, Kerstin; Winkler, Thomas H; Nitschke, Lars

2010-04-01

CD22 and Siglec-G are inhibitory coreceptors for BCR-mediated signaling. Although CD22-deficient mice show increased calcium signaling in their conventional B2 cells and a quite normal B cell maturation, Siglec-G-deficient mice have increased calcium mobilization just in B1 cells and show a large expansion of the B1 cell population. Neither CD22-deficient, nor Siglec-G-deficient mice on a pure C57BL/6 or BALB/c background, respectively, develop autoimmunity. Using Siglec-G x CD22 double-deficient mice, we addressed whether Siglec-G and CD22 have redundant functions. Siglec-G x CD22 double-deficient mice show elevated calcium responses in both B1 cells and B2 cells, increased serum IgM levels and an enlarged population of B1 cells. The enlargement of B1 cell numbers is even higher than in Siglecg(-/-) mice. This expansion seems to happen at the expense of B2 cells, which are reduced in absolute cell numbers, but show an activated phenotype. Furthermore, Siglec-G x CD22 double-deficient mice show a diminished immune response to both thymus-dependent and thymus-independent type II Ags. In contrast, B cells from Siglec-G x CD22 double-deficient mice exhibit a hyperproliferative response to stimulation with several TLR ligands. Aged Siglec-G x CD22 double-deficient mice spontaneously develop anti-DNA and antinuclear autoantibodies. These resulted in a moderate form of immune complex glomerulonephritis. These results show that Siglec-G and CD22 have partly compensatory functions and together are crucial in maintaining the B cell tolerance.

Kawasaki disease with G6PD deficiency--report of one case and literature review.

PubMed

Chen, Chia-Hao; Lin, Li-Yan; Yang, Kuender D; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2014-06-01

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are younger than 5 years. The most serious complications are coronary artery aneurysms and sequelae of vasculitis with the subsequent development of coronary artery aneurysm. According to the literature, intravenous immunoglobulin (IVIG) plus high-dose aspirin (acetylsalicylic acid) were standard treatment for KD, whereas low-dose aspirin (3-5 mg/kg/day) was used for thrombocytosis in KD via antiplatelet effect. However, aspirin has been reported to have hemolytic potential in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a child with G6PD-deficiency who has KD, and review the literature. Copyright © 2012. Published by Elsevier B.V.

Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency.

PubMed

Belfield, Kristen D; Tichy, Eric M

2018-02-01

The pathophysiology, diagnosis, and medication-use implications of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzyme deficiency in humans, are reviewed. Originally identified as favism in patients who experienced hemolysis after ingestion of fava beans, G6PD deficiency results from an X-linked chromosomal mutation that leads to reduced activity of the enzyme responsible for the final step of the pentose phosphate pathway, through which reduced nicotinamide adenine dinucleotide phosphate required for protection of cells from oxidative stress is produced. G6PD deficiency affects about 400 million people worldwide. Diagnosis of G6PD can be made through detection of enzymatic activity (by spectrophotometric testing, fluorescence testing, or formazan-based spot testing) or molecular analysis to detect known mutations of the gene encoding G6PD. Most individuals with G6PD deficiency are asymptomatic throughout life. Symptoms of acute hemolysis associated with G6PD deficiency include anemia, fatigue, back or abdominal pain, jaundice, and hemoglobinuria. The most common precipitators of oxidative stress and hemolysis in G6PD deficiency include medication use and infection. G6PD deficiency should be considered in patients who experience acute hemolysis after exposure to known oxidative medications, infection, or ingestion of fava beans. A diagnosis of G6PD deficiency is most often made through enzymatic activity detection, but molecular analysis may be required in females heterozygous for the disorder. When clinically feasible, rasburicase, primaquine, dapsone, pegloticase, and methylene blue should not be used until a G6PD diagnostic test has been performed. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Aberrant antibody affinity selection in SHIP-deficient B cells.

PubMed

Leung, Wai-Hang; Tarasenko, Tatiana; Biesova, Zuzana; Kole, Hemanta; Walsh, Elizabeth R; Bolland, Silvia

2013-02-01

The strength of the Ag receptor signal influences development and negative selection of B cells, and it might also affect B-cell survival and selection in the GC. Here, we have used mice with B-cell-specific deletion of the 5'-inositol phosphatase SHIP as a model to study affinity selection in cells that are hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP, B cells have lower thresholds for Ag- and interferon (IFN)-induced activation, resulting in augmented negative selection in the BM and enhanced B-cell maturation in the periphery. Despite a tendency to spontaneously downregulate surface IgM expression, SHIP deficiency does not alter anergy induction in response to soluble hen-egg lysozyme Ag in the MDA4 transgenic model. SHIP-deficient B cells spontaneously produce isotype-switched antibodies; however, they are poor responders in immunization and infection models. While SHIP-deficient B cells form GCs and undergo mutation, they are not properly selected for high-affinity antibodies. These results illustrate the importance of negative regulation of B-cell responses, as lower thresholds for B-cell activation promote survival of low affinity and deleterious receptors to the detriment of optimal Ab affinity maturation. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glucose-6-phosphate dehydrogenase deficiency: not exclusively in males.

PubMed

van den Broek, Leonie; Heylen, Evelien; van den Akker, Machiel

2016-12-01

Glucose-6-phosphate (G6PD) deficiency is the most common human enzyme defect, often presenting with neonatal jaundice and/or acute hemolytic anemia, triggered by oxidizing agents. G6PD deficiency is an X-linked, hereditary disease, mainly affecting men, but should also be considered in females with an oxidative hemolysis.

B vitamins and the aging brain.

PubMed

Selhub, Jacob; Troen, Aron; Rosenberg, Irwin H

2010-12-01

Deficiencies of the vitamins folate, B(12) , and B(6) are associated with neurological and psychological dysfunction and with congenital defects. In the elderly, cognitive impairment and incident dementia may be related to the high prevalence of inadequate B vitamin status and to elevations of plasma homocysteine. Plausible mechanisms include homocysteine neurotoxicity, vasotoxicity, and impaired S-adenosylmethionine-dependent methylation reactions vital to central nervous system function. In light of this, it is imperative to find safe ways of improving vitamin B status in the elderly without exposing some individuals to undue risk. © 2010 International Life Sciences Institute.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Sichuan, China.

PubMed

Zhang, Jing; Cui, Yali; Wang, Xia; Li, Yingying; Jiang, Dongmei; Dai, Wei; Jiang, Yongmei

2018-03-01

Our goals were to screen newborns and characterize the occurrence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southwestern China. Meanwhile, we would like to analyze the factors that might affect the results of neonatal dried blood spots for glucose-6-phosphate dehydrogenase screening test, to improve the clinical quality control level, effectively reduce the external factors in the process of detection. This study involved an evaluation of G6PD data for 20,644 newborns from a universal newborn screening program. Heel prick blood specimens were collected around 72 hours after birth and were dried on filter papers. For G6PD deficiency the fluorescent spot test was employed. We studied the association between incidence of G6PD deficiency and influence factors. This study involved an evaluation of G6PD data for 20,644 neonatal heel prick blood samples from 10,984 males and 9,660 females. There were 503 positive results for G6PD deficiency (299 males and 204 females), and the G6PD deficiency-positive rate was estimated to be around 2.4%. The gender-specific prevalence for males was 2.7%, and for females 2.1%. Multiple factors may influence the result of the G6PD test, such as season, temperature, and specimen of indwelling time. This study analyzed the prevalence of G6PD deficiency in Sichuan, China. Accelerating the speed of sample delivery and ensuring availability of screening results can aid the screening and diagnosis.

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.

PubMed

Vrolijk, Misha F; Opperhuizen, Antoon; Jansen, Eugène H J M; Hageman, Geja J; Bast, Aalt; Haenen, Guido R M M

2017-10-01

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does Abiotic Stress Cause Functional B Vitamin Deficiency in Plants?1[OPEN

PubMed Central

Beaudoin, Guillaume A.; Gregory, Jesse F.

2016-01-01

B vitamins are the precursors of essential metabolic cofactors but are prone to destruction under stress conditions. It is therefore a priori reasonable that stressed plants suffer B vitamin deficiencies and that certain stress symptoms are metabolic knock-on effects of these deficiencies. Given the logic of these arguments, and the existence of data to support them, it is a shock to realize that the roles of B vitamins in plant abiotic stress have had minimal attention in the literature (100-fold less than hormones) and continue to be overlooked. In this article, we therefore aim to explain the connections among B vitamins, enzyme cofactors, and stress conditions in plants. We first outline the chemistry and biochemistry of B vitamins and explore the concept of vitamin deficiency with the help of information from mammals. We then summarize classical and recent evidence for stress-induced vitamin deficiencies and for plant responses that counter these deficiencies. Lastly, we consider potential implications for agriculture. PMID:27807106

Vitamin-D deficiency predicts infections in young north Indian children: A secondary data analysis.

PubMed

Chowdhury, Ranadip; Taneja, Sunita; Bhandari, Nita; Sinha, Bireshwar; Upadhyay, Ravi Prakash; Bhan, Maharaj Kishan; Strand, Tor A

2017-01-01

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children. We used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Generalized estimating equations (GEE) were used to examine the associations between vitamin-D deficiency and episodes of ALRI, clinical pneumonia and diarrhea. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status and season), that the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not associated with episodes of diarrhea or clinical pneumonia. Vitamin-D deficiency is common in young children in New Delhi and is associated with a higher risk of ALRI. The role of vitamin D in Indian children needs to be elucidated in further studies.

Deficiencies Under Plenty of Sun: Vitamin D Status among Adults in the Kingdom of Saudi Arabia, 2013.

PubMed

Tuffaha, Marwa; El Bcheraoui, Charbel; Daoud, Farah; Al Hussaini, Hessah Abdulla; Alamri, Fahad; Al Saeedi, Mohammad; Basulaiman, Mohammed; Memish, Ziad A; AlMazroa, Mohammad A; Al Rabeeah, Abdullah A; Mokdad, Ali H

2015-10-01

Vitamin D deficiency has been correlated with several diseases and injuries including diabetes, osteoporosis, fractures, and falls. In the Kingdom of Saudi Arabia (KSA), current data on vitamin D status are lacking. To inform Saudi public health authorities on the current status of blood levels vitamin D deficiency, we analyzed data from the Saudi Health Interview Survey. The Saudi Health Interview Survey (SHIS) is a cross-sectional national multistage survey of individuals aged 15 years and above on sociodemographic characteristics, tobacco consumption, diet, physical activity, health care utilization, different health-related behaviors, and self-reported chronic conditions. A total of 10,735 participants completed a health questionnaire and were invited to the local health clinics for biomedical exams. 62.65% of female Saudis and 40.6% of male Saudis aged 15 years and above are deficient in vitamin D. Out of them, less than 1% males and less than 2% females consume vitamin D supplements. Women who have never married and obese individuals are more likely to be deficient in vitamin D, compared to men who were currently married and nonobese individuals. Those consuming vitamin D supplements are less likely to be deficient in vitamin D. Our study showed a high prevalence of vitamin D deficiency among Saudi men and women, and the results call for an increased awareness to ensure adequate levels of vitamin D for better health in Saudi Arabia. Moreover, our findings are certainly relevant for other countries in the Gulf region or countries with similar cultures, clothing, and religions.

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification1234

PubMed Central

Morris, Martha Savaria; Jacques, Paul F; Rosenberg, Irwin H; Selhub, Jacob

2007-01-01

Background Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. Objective We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <34) in senior participants in the 1999–2002 US National Health and Nutrition Examination Survey. Design The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration <148 pmol/L or a serum methylmalonic acid concentration >210 nmol/L—the maximum of the reference range for serum vitamin B-12–replete participants with normal creatinine. Results After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate ≤59 nmol/L (80th percentile), as opposed to ≤59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were <1.0 (Pinteraction <0.05), but significantly <1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). Conclusion In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When

Priapism and glucose-6-phosphate dehydrogenase deficiency: An underestimated correlation?

PubMed

De Rose, Aldo Franco; Mantica, Guglielmo; Tosi, Mattia; Bovio, Giulio; Terrone, Carlo

2016-10-05

Priapism is a rare clinical condition characterized by a persistent erection unrelated to sexual excitement. Often the etiology is idiopathic. Three cases of priapism in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients have been described in literature. We present the case of a 39-year-old man with glucose- 6-phosphate dehydrogenase deficiency, who reached out to our department for the arising of a non-ischemic priapism without arteriolacunar fistula. We suggest that the glucose-6-phosphate dehydrogenase deficiency could be an underestimated risk factor for priapism.

Is glucose-6-phosphate dehydrogenase deficiency more prevalent in Carrion's disease endemic areas in Latin America?

PubMed

Mazulis, Fernando; Weilg, Claudia; Alva-Urcia, Carlos; Pons, Maria J; Del Valle Mendoza, Juana

2015-12-01

Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme with an important function in cell oxidative damage prevention. Erythrocytes have a predisposition towards oxidized environments due to their lack of mitochondria, giving G6PD a major role in its stability. G6PD deficiency (G6PDd) is the most common enzyme deficiency in humans; it affects approximately 400 million individuals worldwide. The overall G6PDd allele frequency across malaria endemic countries is estimated to be 8%, corresponding to approximately 220 million males and 133 million females. However, there are no reports on the prevalence of G6PDd in Andean communities where bartonellosis is prevalent. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination.

PubMed

Tabatabaei, Seyed Mehdi; Salimi Khorashad, Alireza; Sakeni, Mohammad; Raeisi, Ahmad; Metanat, Zahra

2015-03-15

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions. It is an obstacle to malaria elimination, as primaquine administered in the treatment of malaria can cause hemolysis in G6PD-deficient individuals. This study presents information on the prevalence of G6PD deficiency in Sistan and Balouchetsan province, which hosts more than 90% of Plasmodium vivax malaria cases in Iran. This type of information is needed for a successful malaria elimination program. A total of 526 students were randomly recruited through schools located in southeast Iran. Information was collected by interviewing the students using a structured questionnaire. Blood samples taken on filter papers were examined for G6PD deficiency using the fluorescent spot test. Overall, 72.8% (383/526) of the subjects showed normal G6PD enzyme function. Mild and severe G6PD deficiency was observed in 14.8% (78) and 12.2% (64) of subjects, respectively. A total 193/261 males (73.9%) and 190/265 (72%) females had normal enzyme activity. Mild G6PD deficiency was observed in 10.8% (28) and 18.9% (50) of male and female subjects, respectively. However, in comparison with females, a greater proportion of males showed severe enzyme deficiency (15.3% versus 9.1%). All these differences were statistically significant (p < 0.006). G6PD deficiency is highly prevalent in southeast Iran. G6PD-deficient individuals are susceptible to potentially severe and life-threatening hemolytic reactions after primaquine treatment. In order to achieve malaria elimination goals in the province, G6PD testing needs to be made routinely available within the health system.

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

PubMed Central

Bawcom, Amanda; Romano, Mary E.

2014-01-01

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient’s diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.1 PMID:25367534

Cobalamin C deficiency in an adolescent with altered mental status and anorexia.

PubMed

Rahmandar, Maria H; Bawcom, Amanda; Romano, Mary E; Hamid, Rizwan

2014-12-01

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient's diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.(1.) Copyright © 2014 by the American Academy of Pediatrics.

Hyperhomocysteinemia and vitamin B-12 deficiency are more striking in Syrians than in Germans--causes and implications.

PubMed

Herrmann, Wolfgang; Obeid, Rima; Jouma, Muhidien

2003-01-01

Hyperhomocysteinemia is an accepted risk factor for coronary artery disease, but the determining factors are not fully understood. We investigated hyperhomocysteinemia and vitamin deficiency in Syrian coronary patients and apparently healthy Syrian and German controls. We enrolled 273 Syrian patients with angiographically confirmed stenosis, along with 159 Syrian and 75 German controls. Plasma total homocysteine (HCY), cystathionine, methylmalonic acid (MMA), vitamin B-6, B-12, folate, lipids, apolipoproteins and methylenetetrahydrofolate reductase (C677T-MTHFR) mutation were analysed. There was a very high prevalence of hyperhomocysteinemia (>12 micromol/l) in Syrians (patients 61%, controls 44%, Germans 16%) together with functional vitamin B-12 deficiency diagnosed by elevated MMA (patients 49%, controls 47%, Germans 3%), which was in contrast to the low frequency of decreased serum vitamin B-12 (12% in patients, 7% in Syrian controls). The HCY concentration in German controls was lower than in Syrians, median 8.8 vs. 11.3 micromol/l. The vitamin B-12 deficiency induces folate trapping; higher levels of folate are needed to prevent hyperhomocysteinemia. Germans achieved the HCY level of < or =12 micromol/l at significantly lower folate concentrations > or =4.4 ng/ml, than Syrians with normal MMA (> or =16.7 nmol/l folate) or Syrians with high MMA (> or =23.3 nmol/l folate). Smoking and homozygous state for C677T-MTHFR mutation contributed to hyperhomocysteinemia. We could confirm that the reasons for hyperhomocysteinemia in Syrians were in fact mostly related to a relative folate deficiency, which is due to a vitamin B-12 shortage. Vitamin B-12 deficiency induces folate trapping. Besides lifestyle, other presently unknown factors may contribute to hyperhomocysteinemia and vitamin B-12 deficiency in Syrians.

Dissimilar Deficiency of Glucose-6-Phosphate Dehydrogenase (G-6-PD) among the AFARS and the Somalis of Djibouti

DTIC Science & Technology

1991-01-01

DEFICIENCY OF GLUCOSE - 6 - PHOSPHATE DEHYDROGENASE (G- 6 ...the prevalence of deficient activity of the enzyme glucose - 6 - phosphate dehydrogenase (G- 6 -PD) among - Ces difficiences enzymatiques sant plus particu...Screening for glucose - 6 - 3 - CaosBy W.H. - Hematologic diseases. In : I lunter’s Tropical phosphate dehydrogenase (G- 6 -PD) deficiency by a simple

Vitamin B12 and folate deficiency in chronic heart failure.

PubMed

van der Wal, Haye H; Comin-Colet, Josep; Klip, Ijsbrand T; Enjuanes, Cristina; Grote Beverborg, Niels; Voors, Adriaan A; Banasiak, Waldemar; van Veldhuisen, Dirk J; Bruguera, Jordi; Ponikowski, Piotr; Jankowska, Ewa A; van der Meer, Peter

2015-02-01

To determine the prevalence, clinical correlates and the effects on outcome of vitamin B12 and folic acid levels in patients with chronic heart failure (HF). We studied an international pooled cohort comprising 610 patients with chronic HF. The main outcome measure was all-cause mortality. Mean age of the patients was 68±12 years and median serum N-terminal prohormone brain natriuretic peptide level was 1801 pg/mL (IQR 705-4335). Thirteen per cent of the patients had an LVEF >45%. Vitamin B12 deficiency (serum level <200 pg/mL), folate deficiency (serum level <4.0 ng/mL) and iron deficiency (serum ferritin level <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) were present in 5%, 4% and 58% of the patients, respectively. No significant correlation between mean corpuscular volume and vitamin B12, folic acid or ferritin levels was observed. Lower folate levels were associated with an impaired health-related quality of life (p=0.029). During a median follow-up of 2.10 years (1.31-3.60 years), 254 subjects died. In multivariable proportional hazard models, vitamin B12 and folic acid levels were not associated with prognosis. Vitamin B12 and folate deficiency are relatively rare in patients with chronic HF. Since no significant association was observed between mean corpuscular volume and neither vitamin B12 nor folic acid levels, this cellular index should be used with caution in the differential diagnosis of anaemia in patients with chronic HF. In contrast to iron deficiency, vitamin B12 and folic acid levels were not related to prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Vitamin B-12 supplementation of rural Mexican women changes biochemical vitamin B-12 status indicators but does not affect hematology or a bone turnover marker.

PubMed

Shahab-Ferdows, Setareh; Anaya-Loyola, Miriam A; Vergara-Castañeda, Haydé; Rosado, Jorge L; Keyes, William R; Newman, John W; Miller, Joshua W; Allen, Lindsay H

2012-10-01

A high prevalence of low serum vitamin B-12 concentrations has been reported in studies and surveys in Latin America including Mexico, but the functional consequences are unknown. This randomized controlled trial assessed the response to a high-dose vitamin B-12 supplementation of women in rural Querétaro, Mexico. Participants aged 20-59 y were stratified at baseline to deficient, marginal, and adequate status groups (serum vitamin B-12, 75-148, 149-220, and >220 pmol/L, respectively), and each group was randomized to vitamin B-12 treatment (single dose of 1 mg i.m. then 500 μg/d orally for 3 mo, n = 70) or placebo (n = 62). Measures at baseline and 3 mo included: complete blood count, serum vitamin B-12, holotranscobalamin (holoTC), folate, ferritin, C-reactive protein (CRP), bone alkaline phosphatase, and methylmalonic acid (MMA) and plasma total homocysteine (tHcy). At baseline, 11% of the women were vitamin B-12 deficient and 22% had marginal status. HoloTC was low (<35 pmol/L) in 23% and correlated with serum vitamin B-12 (r = 0.7; P < 0.001). Elevated MMA (>271 nmol/L) and tHcy (>12 μmol/L) occurred in 21 and 31%, respectively, and correlated with serum vitamin B-12 (r = -0.28, P < 0.0007 and r = -0.20, P < 0.01, respectively). Supplementation increased serum vitamin B-12 and holoTC and lowered MMA and tHcy, normalizing all values except for elevated tHcy in 21% of the women. Supplementation did not affect hematology or bone-specific alkaline phosphatase. Vitamin B-12 supplementation normalized biochemical indicators of vitamin B-12 status in the treatment group but did not affect the functional outcomes measured.

Thiamine Deficiency Complex Workshop final report: November 6-7, 2008, Ann Arbor, MI

USGS Publications Warehouse

Honeyfield, Dale C.; Tillitt, Donald E.; Riley, Stephen C.

2008-01-01

Fry mortality which was first observed in the late 1960s in Great Lakes salmonines and in Baltic Sea salmon in 1974 has now been linked to thiamine deficiency (historically referred to as Early Mortality Syndrome, or EMS and M74, respectively). Over the past 14 years significant strides have been made in our understanding of this perplexing problem. It is now known that thiamine deficiency causes embryonic mortality in these salmonids. Both overt mortality and secondary effects of thiamine deficiency are observed in juvenile and adult animals. Collectively the morbidity and mortality (fry and adult mortality, secondary metabolic and behavior affects in juveniles and adult fish) are referred to as Thiamine Deficiency Complex (TDC). A workshop was held in Ann Arbor, MI on 6-7 November 2008 that brought together 38 federal, state, provincial, tribal and university scientists to share information, present data and discuss the latest observations on thiamine status of aquatic animals with thiamine deficiency and the causative agent, thiaminase. Twenty presentations (13 oral and 7 posters) detailed current knowledge. In Lake Huron, low alewife Alosa pseudoharengus abundance has persisted and egg thiamine concentrations in salmonines continue to increase, along with evidence of natural reproduction in lake trout Salvelinus namaycush. Lake Michigan Chinook salmon Oncorhynchus tshawytscha appear to have a lower thiamine requirement than other salmonids in the lake. Lake Ontario American eel Anguilla rostrata foraging on alewife have approximately one third the muscle thiamine compared to eels not feeding on alewife, suggesting that eels may be suffering from thiamine deficiency. Secondary effects of low thiamine exist in Great Lakes salmonines and should not be ignored. Thiaminase activity in dreissenid mussels is extremely high but a connection to TDC has not been made. Thiaminase in net plankton was found more consistently in lakes Michigan and Ontario than other lakes

Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario.

PubMed

Mukherjee, Malay B; Colah, Roshan B; Martin, Snehal; Ghosh, Kanjaksha

2015-05-01

It is believed that the tribal people, who constitute 8.6 per cent of the total population (2011 census of India), are the original inhabitants of India. Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity. Deficiency of this enzyme is highly polymorphic in those areas where malaria is/has been endemic. G6PD deficiency was reported from India more than 50 years ago. t0 he prevalence varies from 2.3 to 27.0 per cent with an overall prevalence of 7.7 per cent in different tribal groups. Since the tribal populations live in remote areas where malaria is/has been endemic, irrational use of antimalarial drugs could result in an increased number of cases with drug induced haemolysis. Therefore, before giving antimalarial therapy, routine screening for G6PD deficiency should be undertaken in those tribal communities where its prevalence is high.

Vitamin B-12-fortified toothpaste improves vitamin status in vegans: a 12-wk randomized placebo-controlled study.

PubMed

Siebert, Anne-Kathrin; Obeid, Rima; Weder, Stine; Awwad, Hussain M; Sputtek, Andreas; Geisel, Juergen; Keller, Markus

2017-03-01

Background: The oral application of vitamin B-12 may prevent its deficiency if the vitamin is absorbed via the mucosal barrier. Objectives: We studied the effect of the use of a vitamin B-12-fortified toothpaste on vitamin-status markers in vegans and assessed the efficiency of markers in the identification of vitamin-augmentation status. Design: In this 12-wk, double-blinded, randomized, placebo-controlled study, 76 vegans received either a placebo ( n = 34) or vitamin B-12 ( n = 42) toothpaste. Sixty-six subjects ( n = 30 in the placebo arm; n = 36 in the vitamin B-12 arm) completed the intervention. Serum and plasma concentrations of vitamin B-12, holotranscobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) were measured before and after the intervention. Results: Both postintervention concentrations of vitamin B-12 and holotranscobalamin and their changes over 12 wk were higher in the vitamin B-12 group (mean ± SD change: 81 ± 135 pmol/L for vitamin B-12 and 26 ± 34 pmol/L for holotranscobalamin) than in the placebo group (-27 ± 64 and -5 ± 17 pmol/L, respectively) after adjustment for baseline concentrations. Postintervention concentrations of MMA and their changes differed significantly between groups (MMA changes: -0.169 ± 0.340 compared with -0.036 ± 0.544 μmol/L in vitamin B-12 and placebo groups, respectively; P < 0.001). After adjustment for baseline tHcy, postintervention concentrations of tHcy tended to be lower ( P = 0.051), and the changes in tHcy (-0.7 ± 4.4 compared with 2.0 ± 5.6 μmol/L, respectively) were greater in the vitamin B-12 group than in the placebo group. Changes in vitamin B-12 markers were more prominent in vegans who reported that they had not taken vitamin B-12 supplements. Conclusion: Vitamin B-12 that is applied to the oral cavity via toothpaste enters the circulation and corrects the vitamin B-12 markers in the blood of vegans who are at higher risk of vitamin B-12 deficiency. This trial was registered

Neonatal nucleated red blood cells in G6PD deficiency.

PubMed

Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

2002-05-01

The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

Folate and Vitamin B12 Deficiency Among Non-pregnant Women of Childbearing-Age in Guatemala 2009-2010: Prevalence and Identification of Vulnerable Populations.

PubMed

Rosenthal, Jorge; Lopez-Pazos, Eunice; Dowling, Nicole F; Pfeiffer, Christine M; Mulinare, Joe; Vellozzi, Claudia; Zhang, Mindy; Lavoie, Donna J; Molina, Roberto; Ramirez, Nicte; Reeve, Mary-Elizabeth

2015-10-01

Information on folate and vitamin B12 deficiency rates in Guatemala is essential to evaluate the current fortification program. The objectives of this study were to describe the prevalence of folate and vitamin B12 deficiencies among women of childbearing age (WCBA) in Guatemala and to identify vulnerable populations at greater risk for nutrient deficiency. A multistage cluster probability study was designed with national and regional representation of nonpregnant WCBA (15-49 years of age). Primary data collection was carried out in 2009-2010. Demographic and health information was collected through face-to-face interviews. Blood samples were collected from 1473 WCBA for serum and red blood cell (RBC) folate and serum vitamin B12. Biochemical concentrations were normalized using geometric means. Prevalence rate ratios were estimated to assess relative differences among different socioeconomic and cultural groups including ethnicity, age, education level, wealth index and rural versus urban locality. National prevalence estimates for deficient serum [<10 nmol per liter (nmol/L)] and RBC folate (<340 nmol/L) concentrations were 5.1 % (95 % CI 3.8, 6.4) and 8.9 % (95 % CI 6.7, 11.7), respectively; for vitamin B12 deficiency (<148 pmol/L) 18.5 % (95 % CI 15.6, 21.3). Serum and RBC folate deficiency prevalences were higher for rural areas than for urban areas (8.0 vs. 2.0 % and 13.5 vs. 3.9 %, respectively). The prevalence of RBC folate deficiency showed wide variation by geographic region (3.2-24.9 %) and by wealth index (4.1-15.1 %). The prevalence of vitamin B12 deficiency also varied among regions (12.3-26.1 %). In Guatemala, folate deficiency was more prevalent among indigenous rural and urban poor populations. Vitamin B12 deficiency was widespread among WCBA. Our results suggest the ongoing need to monitor existing fortification programs, in particular regarding its reach to vulnerable populations.

Folate and Vitamin B12 Deficiency Among Nonpregnant Women of Childbearing Age in Guatemala 2009–2010: Prevalence and Identification of Vulnerable Populations

PubMed Central

Rosenthal, Jorge; Lopez-Pazos, Eunice; Dowling, Nicole F.; Pfeiffer, Christine M.; Mulinare, Joe; Vellozzi, Claudia; Zhang, Mindy; Lavoie, Donna J; Molina, Roberto; Ramirez, Nicte; Reeve, Mary-Elizabeth

2015-01-01

Introduction Information on folate and vitamin B12 deficiency rates in Guatemala is essential to evaluate the current fortification program. The objectives of this study were to describe the prevalence of folate and vitamin B12 deficiencies among women of childbearing age (WCBA) in Guatemala and to identify vulnerable populations at greater risk for nutrient deficiency. Methods A multistage cluster probability study was designed with national and regional representation of nonpregnant WCBA (15–49 years of age). Primary data collection was carried out in 2009–2010. Demographic and health information was collected through face-to-face interviews. Blood samples were collected from 1,473 WCBA for serum and red blood cell (RBC) folate and serum vitamin B12. Biochemical concentrations were normalized using geometric means. Prevalence rate ratios were estimated to assess relative differences among different socioeconomic and cultural groups including ethnicity, age, education level, wealth index and rural versus urban locality. Results National prevalence estimates for deficient serum (<10 nanomoles per liter [nmol/L]) and RBC folate (<340 nmol/L) concentrations were 5.1% (95% CI 3.8, 6.4) and 8.9% (95% CI 6.7, 11.7), respectively; for vitamin B12 deficiency (<148 pmol/L) 18.5% (95% CI 15.6, 21.3). Serum and RBC folate deficiency prevalences were higher for rural areas than for urban areas (8.0% vs. 2.0% and 13.5% vs. 3.9%, respectively). The prevalence of RBC folate deficiency showed wide variation by geographic region (3.2%–24.9%) and by wealth index (4.1%–15.1%). The prevalence of vitamin B12 deficiency also varied among regions (12.3% –26.1%). Conclusions In Guatemala, folate deficiency was more prevalent among indigenous rural and urban poor populations. Vitamin B12 deficiency was widespread among WCBA. Our results suggest the ongoing need to monitor existing fortification programs, in particular regarding its reach to vulnerable populations. PMID:26002178

[Molecular analysis of glucose-6-dehydrogenase deficiency in Spain].

PubMed

Vives Corrons, J L; Zarza, R; Aymerich, J M; Boixadera, J; Carrera, A; Colomer, D; Corbella, M; Castro, M; Crespo, J M; Del Arco, A; Erkiaga, S; Font, L; González, I; Juncá, J; Lausin, A; Manrubia, E; Martín Núñez, G; Murga, M J; Oliva, E; Pérez de Mendiguren, B; Pujades, M A; Remacha, A; Rovira, A; Villegas, A

1997-10-01

G6PD deficiency is the most frequent enzymopathy-producing genetic polymorphism in humans. Up to now, over 400 putative variants of G6PD have been distinguished on the basis of biochemical characterization of the deficient enzyme. Analysis of the G6PD gene has made possible a precise classification of the G6PD molecular variants by identification of about 80 different point mutations causing much of the phenotypic heterogeneity. In the Spanish population, the analysis of G6PD has led to the identification of 15 different point mutations that underlay the phenotypic heterogeneity of G6PD previously reported by biochemical analysis. The purpose of the study has been to identify the genetic mutation responsible of the G6PD deficiency and to improve the knowledge of its genetic homogeneity. From 50 Spanish males with G6PD deficiency 34 came from out consultation and 16 from the Spanish Study Group on Red Cell Pathology (GEHBTA-Eritropatología) The methods employed included screening of prevalent mutations by ER-PCR, SSCP-PCR, genetic segmentation and biochemical characterization of the deficient enzyme. In 31 cases the mutations were characteristic of the four most frequent polymorphic variants found in Spain (G6PD A-376G/202A, G6PD Mediterranean 563T G6PD Union 1360T and G6PD Seattle 344C). Since these mutations either create or abolish a specific site recognized by a restriction endonuclease (RE), they can be rapidly detected by RE digestion of a PCR-amplified product (PCR-RE). In patients where none of these mutations were present (17 cases), the G6PD gene was subjected to PCR single-strand conformation polymorphism (PCR-SSCP) analysis combined with direct PCR-sequencing. By using this procedure, 9 new mutations have been identified, five of them have been also found in other geographical areas and were associated with favism (G6PD A-376G/968C, G6PD Santamaria 376G/542T, G6PD Aures 143C and G6PD Chatham 1003A) or chronic haemolytic anaemia (G6PD Tomah 1153C). The

Primaquine-induced haemolysis in females heterozygous for G6PD deficiency.

PubMed

Chu, Cindy S; Bancone, Germana; Nosten, François; White, Nicholas J; Luzzatto, Lucio

2018-03-02

Oxidative agents can cause acute haemolytic anaemia in persons with G6PD deficiency. Understanding the relationship between G6PD genotype and the phenotypic expression of the enzyme deficiency is necessary so that severe haemolysis can be avoided. The patterns of oxidative haemolysis have been well described in G6PD deficient hemizygous males and homozygous females; and haemolysis in the proportionally more numerous heterozygous females has been documented mainly following consumption of fava beans and more recently dapsone. It has long been known that 8-aminoquinolines, notably primaquine and tafenoquine, cause acute haemolysis in G6PD deficiency. To support wider use of primaquine in Plasmodium vivax elimination, more data are needed on the haemolytic consequences of 8-aminoquinolines in G6PD heterozygous females. Two recent studies (in 2017) have provided precisely such data; and the need has emerged for the development of point of care quantitative testing of G6PD activity. Another priority is exploring alternative 8-aminoquinoline dosing regimens that are practical and improve safety in G6PD deficient individuals.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army personnel.

PubMed

Chinevere, Troy D; Murray, Clinton K; Grant, Earl; Johnson, Gregory A; Duelm, Felix; Hospenthal, Duane R

2006-09-01

The U.S. Army recently mandated that soldiers undergo glucose-6-phosphate dehydrogenase (G6PD) testing before deployment to malarious regions. We retrospectively characterize the presence and degree of G6PD deficiency in U.S. military personnel by sex, self-reported ethnicity, and World Health Organization deficiency classification through test results obtained October 1, 2004 through January 17, 2005. Data were available for 63,302 (54,874 males and 8,428 females) subjects; 2.5% of males and 1.6% of females were deficient, with most having only moderate enzyme deficiency. African American males (12.2%) and females (4.1%), along with Asian males (4.3%), had the highest rates of G6PD deficiency. Most males were found to have class III variants while most females were class IV variants. The most severely deficient were Asian males (class II). These results suggest that universal screening for G6PD deficiency is clinically warranted, and particularly essential for those male service members who self-report ethnicity as African American, Asian, or Hispanic.

[Congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency].

PubMed

Mura, M; Saidi, R; Wolf, A; Moalic, J L; Oliver, M

2009-12-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme defect with a wide range of clinical manifestations that can be severe. A variety of factors including many medications can induce hemolytic episodes. Screening for G6PD deficiency is required before use of some drugs especially primaquine or dapsone.

High prevalence of hemoglobin disorders and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Republic of Guinea (West Africa).

PubMed

Millimono, Tamba S; Loua, Kovana M; Rath, Silvia L; Relvas, Luis; Bento, Celeste; Diakite, Mandiou; Jarvis, Martin; Daries, Nathalie; Ribeiro, Leticia M; Manco, Licínio; Kaeda, Jaspal S

2012-01-01

Reliable and accurate epidemiological data is a prerequisite for a cost effective screening program for inherited disorders, which however, is lacking in a number of developing countries. Here we report the first detailed population study in the Republic of Guinea, a sub-Saharan West African country, designed to assess the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies, including screening for thalassemia. Peripheral blood samples from 187 Guinean adults were screened for hemoglobin (Hb) variants by standard hematological methods. One hundred and ten samples from males were screened for G6PD deficiency by the fluorescent spot test. Molecular analysis was performed for the most common α-thalassemia (α-thal) deletions, β-globin gene mutations, G6PD variants B (376A), A (376G), A- (376G/202A) and Betica (376G/968C), using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) or sequencing. Of the 187 subjects screened, 36 were heterozygous for Hb S [β6(A3)Glu→Val, GAG>GTG] (allele frequency 9.62%). Sixty-four subjects were heterozygous and seven were homozygous for the -α(3.7) kb deletion (allele frequency 20.85%). β-Thalassemia alleles were detected in five subjects, four with the -29 (A>G) mutation (allele frequency 1.07%) and one with codon 15 (TGG>TAG) (allele frequency 0.96%). The G6PD A- and G6PD Betica deficient variants were highly prevalent with a frequency of 5.7 and 3.3%, respectively. While we did not test for ferritin levels or α(0)-thal, four females (5.2%) had red cell indices strongly suggestive of iron deficient anemia: Hb <9.7 g/dL; MCH <19.3 pg; MCV <68.2; MCHC <31.6 g/dl; RDW >19.8%. Our results are consistent with high frequency of alleles such as Hb S, α-thal and G6PD deficient alleles associated with malaria resistance. Finding a 9.6% Hb S allele frequency supports the notion for a proficient neonatal screening to identify the sickle cell patients, who might benefit

Prevalence and molecular basis of glucose-6-phosphate dehydrogenase deficiency in Afghan populations: implications for treatment policy in the region

PubMed Central

2013-01-01

Background Glucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition. In endemic areas, including in Afghanistan, the G6PD status of vivax patients is not routinely determined so the drug is rarely, if ever, prescribed even though it is included as a recommended treatment in local, regional and global guidelines. This study assessed the prevalence and genotype of G6PD deficiency in Afghan populations and examined the need for routine G6PD testing as a malaria treatment and control tool. Methods A cross-sectional household survey was conducted using random sampling in five Afghan cities to determine the prevalence of G6PD deficiency in Afghan ethnic groups. Filter-paper blood spots were analysed for phenotypic G6PD deficiency using a fluorescent spot test. Molecular analysis was conducted to identify the genetic basis of the disorder. Results Overall, 45/1,436 (3.1%) people were G6PD deficient, 36/728 (5.0%) amongst males and 9/708 (1.3%) amongst females. Amongst males the prevalence was highest in the Pashtun ethnic group (10%, 26/260) while in Tajik males it was 8/250 (3.2%); in Hazara males it was 1/77 (1.3%) and in Uzbek males is was 0/125. Genetic testing in those with deficiency showed that all were of the Mediterranean type (Med-) characterized by a C-T change at codon 563 of the G6PD gene. Conclusion Prevalence of G6PD deficiency in Afghanistan varies considerably by ethnic group and is predominantly of the Mediterranean type. G6PD deficient individuals are susceptible to potentially severe and life-threatening haemolysis after standard primaquine treatment. If the aim of increasing access to radical treatment of vivax is to be successful reliable G6PD testing needs to be made routinely available within the health system. PMID:23834949

Prevalence and molecular basis of glucose-6-phosphate dehydrogenase deficiency in Afghan populations: implications for treatment policy in the region.

PubMed

Leslie, Toby; Moiz, Bushra; Mohammad, Nader; Amanzai, Omar; Ur Rasheed, Haroon; Jan, Sakhi; Siddiqi, Abdul M; Nasir, Amna; Beg, Mohammad A; Vink, Martijn

2013-07-08

Glucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition. In endemic areas, including in Afghanistan, the G6PD status of vivax patients is not routinely determined so the drug is rarely, if ever, prescribed even though it is included as a recommended treatment in local, regional and global guidelines. This study assessed the prevalence and genotype of G6PD deficiency in Afghan populations and examined the need for routine G6PD testing as a malaria treatment and control tool. A cross-sectional household survey was conducted using random sampling in five Afghan cities to determine the prevalence of G6PD deficiency in Afghan ethnic groups. Filter-paper blood spots were analysed for phenotypic G6PD deficiency using a fluorescent spot test. Molecular analysis was conducted to identify the genetic basis of the disorder. Overall, 45/1,436 (3.1%) people were G6PD deficient, 36/728 (5.0%) amongst males and 9/708 (1.3%) amongst females. Amongst males the prevalence was highest in the Pashtun ethnic group (10%, 26/260) while in Tajik males it was 8/250 (3.2%); in Hazara males it was 1/77 (1.3%) and in Uzbek males is was 0/125. Genetic testing in those with deficiency showed that all were of the Mediterranean type (Med-) characterized by a C-T change at codon 563 of the G6PD gene. Prevalence of G6PD deficiency in Afghanistan varies considerably by ethnic group and is predominantly of the Mediterranean type. G6PD deficient individuals are susceptible to potentially severe and life-threatening haemolysis after standard primaquine treatment. If the aim of increasing access to radical treatment of vivax is to be successful reliable G6PD testing needs to be made routinely available within the health system.

Does G6PD deficiency protect against cancer? A critical review.

PubMed Central

Cocco, P

1987-01-01

Previous observations on the lower mortality for cancer experienced in populations with a higher frequency of G6PD deficiency support biochemical studies on the role of G6PD during cell proliferation. The general agreement among experimental studies prevented a deeper analysis of the sources of what has been called "epidemiological evidence of the protective role of G6PD deficiency against cancer". This review analyses the methods and findings in those papers, stressing their limitations and emphasising that no final conclusions can be drawn from them. Preliminary results of ongoing epidemiological studies of G6PD deficiency and cancer are presented, although they do not prove or disprove the hypothesis that G6PD deficiency protects against cancer. PMID:3309118

B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells

PubMed Central

Shen, Ping; Brown, Sheila; Lampropoulou, Vicky; Roch, Toralf; Lawrie, Sarah; Fan, Boli; O’Connor, Richard A.; Anderton, Stephen M.; Bar-Or, Amit; Fillatreau, Simon; Gray, David

2012-01-01

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS. PMID:22547654

Anemia and Iron Deficiency in Vietnamese Children, 6 to 11 Years Old.

PubMed

Le Nguyen Bao, Khanh; Tran Thuy, Nga; Nguyen Huu, Chinh; Khouw, Ilse; Deurenberg, Paul

2016-07-01

In a population sample of 385 children, 6 to 11 years old, venous blood parameters-hemoglobin (Hb), ferritin, red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), C-reactive protein (CRP), and α1-acid glycoprotein (AGP)-were determined to get insight into the iron status. The prevalence of anemia was 11.4%; 5.6% had iron deficiency (ID), whereas 0.4% had ID anemia. Correction for inflammation based on CRP and AGP did not markedly change the overall prevalence of ID and ID anemia. Stunted children had lower Hb and ferritin values compared with nonstunted children, and thin children had lower values compared with normal-weight or overweight and obese children. Many nonanemic children had alert values for RBC, MCV, MCH, and MCHC. It is concluded that although the prevalence of anemia is of the magnitude of a mild public health problem, the iron status of many nonanemic children is borderline, as indicated by a high number of children with low values for red blood cytology. © 2016 APJPH.

[Severe vitamin B12 deficiency in infants breastfed by vegans].

PubMed

Roed, Casper; Skovby, Flemming; Lund, Allan Meldgaard

2009-10-19

Weight loss and reduction of motor skills resulted in paediatric evaluation of a 10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and delayed development due to vitamin B12 deficiency caused by strict maternal vegan diet during pregnancy and nursing. Therapy with cyanocobalamin was instituted with remission of symptoms. Since infants risk irreversible neurologic damage following severe vitamin B12 deficiency, early diagnosis and treatment are mandatory. Vegan and vegetarian women should take vitamin B12 supplementation during the pregnancy and nursing period.

Vitamin B6 in plasma and cerebrospinal fluid of children.

PubMed

Albersen, Monique; Bosma, Marjolein; Jans, Judith J M; Hofstede, Floris C; van Hasselt, Peter M; de Sain-van der Velden, Monique G M; Visser, Gepke; Verhoeven-Duif, Nanda M

2015-01-01

Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce. B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples could not be obtained from healthy children. The influence of sex, age, epilepsy and treatment with anti-epileptic drugs, were investigated. The B6 vitamer composition of plasma (pyridoxal phosphate (PLP) > pyridoxic acid > pyridoxal (PL)) differed from that of CSF (PL > PLP > pyridoxic acid > pyridoxamine). Strong correlations were found for B6 vitamers in and between plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased concentrations of PL and PLP in CSF. We provide concentrations of all B6 vitamers in plasma and CSF of children with intellectual disability (±epilepsy), which can be used in the investigation of known and novel disorders associated with vitamin B6 metabolism as well as in monitoring of the biochemical effects of treatment with vitamin B6.

Vitamin B12 intake and status in early pregnancy among urban South Indian women

PubMed Central

Samuel, Tinu Mary; Duggan, Christopher; Thomas, Tinku; Bosch, Ronald; Rajendran, Ramya; Virtanen, Suvi M; Srinivasan, Krishnamachari; Kurpad, Anura V

2015-01-01

Aim To evaluate the vitamin B12 status of South Indian women in early pregnancy and its relationship with sociodemographic, anthropometry and dietary intake. Methods Cross-sectional study among 366 pregnant urban South Indian women ≤14 weeks of gestation with outcome variables defined as low vitamin B12 blood concentration (<150 pmol/L) and impaired vitamin B12 status [low vitamin B12 plus elevated methylmalonic acid (MMA) >0.26 μmol/L)]. Results Low plasma vitamin B12 concentration was observed in 51.1% of the women, while 42.4% had impaired B12 status. Elevated MMA, elevated homocysteine ( >10 μmol/L) and low erythrocyte folate (<283 nmol/L) was observed among 75.8%, 43.3% and 22.2% of women, respectively. The median (25th, 75th percentile) dietary intake of vitamin B12 was 1.25 (0.86, 1.96) μg/day. Lower maternal body weight was associated with higher vitamin B12 concentration [prevalence ratios (PR) (95% CI) 0.57 (0.39, 0.84)). The predictors of impaired vitamin B12 status were non-use of yoghurt [PR (95%CI) 1.63 (1.03, 2.58)], non-use of fish [PR (95% CI) 1.32 (1.01, 1.71)] and primiparity [PR (95% CI) 1.41 (1.05, 1.90)]. Conclusion A high prevalence of vitamin B12 deficiency in early pregnancy among urban South Indian women was related to primiparity and to a low consumption of yoghurt and fish. PMID:23344013

Helicobacter pylori associated vitamin B12 deficiency, pernicious anaemia and subacute combined degeneration of the spinal cord.

PubMed

Gowdappa, H Basavana; Mahesh, M; Murthy, K V K S N; Narahari, M G

2013-09-30

A 23-year-old man presented with weakness in the lower limbs, numbness in hands and feet over past 6 months. Examination revealed a combination of absent ankle jerk, extensor plantar response and reduced sensations in a glove and stocking distribution. MRI of the spinal cord was distinctive of subacute combined degeneration (SACD) of the spinal cord. Serum vitamin B12 was low and anti-intrinsic factor antibodies were positive. A biopsy of the stomach revealed intense inflammatory infiltrates in lamina propria with grade III Helicobacter pylori infection. Other work-up for the cause of vitamin B12 deficiency was unremarkable. H pylori infection triggers autoantibodies by a mechanism of molecular mimicry. This case report highlights H pylori as a causative agent in vitamin B12 deficiency and culminating in SACD of the spinal cord. H pylori treatment reverses the underlying pathogenesis and corrects vitamin B12 deficient state in selected individuals.

Ultrasound-Guided Regional Anesthesia in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Geriatric Trauma Patient

PubMed Central

Födinger, Agnes M.; Kammerlander, Christian; Luger, Thomas J.

2012-01-01

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzymatic disorder causing hemolytic anemia. Exposure to drugs is considered to be the most common cause of acute hemolysis in patients with G6PD deficiency. Experience with regional anesthesia, in particular peripheral nerve blocks, is rarely described in patients with G6PD deficiency, but is of great clinical interest. For this reason, we now report on the successful management of ultrasound-guided axillary brachial plexus block in a patient with geriatric G6PD deficiency. Case report: A female, 75-year-old geriatric trauma patient with G6PD deficiency and a fracture of the left forearm, was scheduled for osteosynthesis of the left forearm. For surgery regional anesthesia with ultrasound-guided axillary brachial plexus block with 30 mL bupivacaine 0.5% was established. Surgical operation und postoperative course were uneventful and with no signs of hemolysis. Conclusion: Ultrasound-guided axillary brachial plexus block with bupivacaine was a safe and effective technique in this patient with G6PD deficiency. Peripheral nerve block is a major analgesic approach and of great value for anesthesiologists and surgeons, especially in our aging and multimorbid society. PMID:23569708

Anemia and Micronutrient Status of Women of Childbearing Age and Children 6–59 Months in the Democratic Republic of the Congo

PubMed Central

Harvey-Leeson, Sarah; Karakochuk, Crystal D.; Hawes, Meaghan; Tugirimana, Pierrot L.; Bahizire, Esto; Akilimali, Pierre Z.; Michaux, Kristina D.; Lynd, Larry D.; Whitfield, Kyly C.; Moursi, Mourad; Boy, Erick; Foley, Jennifer; McLean, Judy; Houghton, Lisa A.; Gibson, Rosalind S.; Green, Tim J.

2016-01-01

Little is known about the micronutrient status of women and children in the Democratic Republic of the Congo, which is critical for the design of effective nutrition interventions. We recruited 744 mother-child pairs from South Kivu (SK) and Kongo Central (KC). We determined hemoglobin (Hb), serum zinc, vitamin B12, folate, ferritin, soluble transferrin receptor (sTfR), retinol binding protein (RBP), C-reactive protein, and α-1 acid glycoprotein concentrations. Anemia prevalence was determined using Hb adjusted for altitude alone and Hb adjusted for both altitude and ethnicity. Anemia prevalence was lower after Hb adjustment for altitude and ethnicity, compared to only altitude, among women (6% vs. 17% in SK; 10% vs. 32% in KC), children 6–23 months (26% vs. 59% in SK; 25% vs. 42% in KC), and children 24–59 months (14% vs. 35% in SK; 23% vs. 44% in KC), respectively. Iron deficiency was seemingly higher with sTfR as compared to inflammation-adjusted ferritin among women (18% vs. 4% in SK; 21% vs. 5% in KC), children 6–23 months (51% vs. 14% in SK; 74% vs. 10% in KC), and children 24–59 months (23% vs. 4% in SK; 58% vs. 1% in KC). Regardless of indicator, iron deficiency anemia (IDA) never exceeded 3% in women. In children, IDA reached almost 20% when sTfR was used but was only 10% with ferritin. Folate, B12, and vitamin A (RBP) deficiencies were all very low (<5%); RBP was 10% in children. The prevalence of anemia was unexpectedly low. Inflammation-adjusted zinc deficiency was high among women (52% in SK; 58% in KC), children 6–23 months (23% in SK; 20% in KC), and children 24–59 months (25% in SK; 27% in KC). The rate of biochemical zinc deficiency among Congolese women and children requires attention. PMID:26901219

Vitamin B12 deficiency might be related to sarcopenia in older adults.

PubMed

Bulut, Esra Ates; Soysal, Pinar; Aydin, Ali Ekrem; Dokuzlar, Ozge; Kocyigit, Suleyman Emre; Isik, Ahmet Turan

2017-09-01

Sarcopenia and dynapenia are related to repeated falls, mobility restriction, depression, frailty, increased mortality and morbidity. The aim of this study is to evaluate the relationship between vitamin B12 deficiency and sarcopenia in older adults. 403 patients, who attended to outpatient clinic and underwent comprehensive geriatric assessment, were included study. All cases' skeletal muscle mass (SMM), walking speed and hand grip strength were recorded by bioimpedance, 4meter walking test and hand dynamometer respectively. The diagnosis of sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older People. Sarcopenia was accepted low SMM with low handgrip strength or low physical performance. Dynapenia was defined as handgrip strength <30kg (men) and <20kg (women). The prevalence of sarcopenia and dynapenia was 24.8% and 32.0%, respectively. In the patients with sarcopenia, mean age, osteoporosis and frailty were higher, and MMSE, and instrumental ADL scores were lower than the patients without sarcopenia (p<0.05). The frequency of sarcopenia and dynapenia were 31.6% and 35.4%, respectively, in patients with vitamin B12 levels <400pg/mL. In addition lean body mass, total skeletal mass and skeletal muscle mass index were lower in the patients with vitamin B12 levels <400pg/mL compared to higher than 400pg/mL (p<0.05). Sarcopenia, which results in lots of negative clinical outcomes in older adults, might be related to vitamin B12 deficiency. Therefore, these patients should be periodically examined for vitamin B12 deficiency due to the potential negative clinical outcomes such as sarcopenia in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt.

PubMed

Elella, Soheir Abo; Tawfik, Mahaa; Barseem, Naglaa; Moustafa, Wafaa

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder which causes neonatal jaundice in most cases, and under certain conditions, can cause a spectrum of hemolytic manifestations. To determine the local prevalence of G6PD deficiency in newborns. Cross-sectional. University hospital. Infants born during 2015 were prospectively screened for G6PD deficiency. Dried blood spot samples on filter paper were collected in collaboration with the central laboratories of the Ministry of Health. Quantitative measurement of G6PD enzyme activity was measured from the blood samples using fluorometric analysis. A value.

Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests

PubMed Central

2013-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. Methods Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. Results Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. Conclusions A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid

Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests.

PubMed

Kahn, Maria; LaRue, Nicole; Bansil, Pooja; Kalnoky, Michael; McGray, Sarah; Domingo, Gonzalo J

2013-08-20

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of

Interventions with vitamins B6, B12 and C in pregnancy.

PubMed

Dror, Daphna K; Allen, Lindsay H

2012-07-01

The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support

Review: mechanisms for boron deficiency-mediated changes in plant water relations.

PubMed

Wimmer, Monika A; Eichert, Thomas

2013-04-01

Boron (B) is an essential microelement for plants and is constantly needed throughout the plant life due to its function as a structural element of the plant cell wall. B deficiency is a wide-spread problem in agricultural areas world-wide, and management of B nutrition is challenged by sudden occurrences of B deficiency or inconsistent effects of foliar B application. The effects of insufficient B supply on different structures relevant for the plant water status have been heavily researched, but the resulting conclusions are contradictory and no clear picture has so far emerged that fully explains the inconsistencies. B deficiency can affect water uptake by inhibition of root and shoot growth and by upregulation of water channels. Structural damage to xylem vessels can limit water transport to arial plant parts, while water loss can be altered by impaired barrier functions of leaf surfaces and reduced photosynthesis. In consequence of all these effects, transpiration is reduced in B-deficient plants under well-watered conditions. Under drought conditions, the responsiveness of stomata is impaired. Possible consequences of damaged vasculature for plant B nutrition include the reduced effectiveness of foliar B fertilization, especially in species with high B phloem mobility. Changes in leaf surface properties can further reduce B uptake after foliar application. In species with low B phloem mobility, weakened xylem vessels may not be able to supply sufficient B to arial parts under conditions of increased B demand, such as during bud development of trees. Since structural damage to vessels is hardly reversible, these effects could be permanent, even if B deficiency was only transient. Another consequence of reduced water status is the higher susceptibility of B-deficient plants to other abiotic stresses, which also impair water relations, especially drought. Since damage to vasculature can occur before visible symptoms of B deficiency appear in shoots, the

Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease

PubMed Central

Hecker, Peter A.; Leopold, Jane A.; Gupte, Sachin A.; Recchia, Fabio A.

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes. PMID:23241320

Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus

PubMed Central

Ho, Hung-Yao; Chen, Lei-Chin; Chen, Chien-Cheng; Shu, Jwu-Ching

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells. PMID:24223971

Biochemical and cytochemical evaluation of heterozygote individuals with glucose-6-phosphate dehydrogenase deficiency.

PubMed

Gurbuz, Nilgun; Aksu, Tevfik Aslan; Van Noorden, Cornelis J F

2005-01-01

The aim of this study was to diagnose heterozygous glucose-6-phosphate dehydrogenase (G6PD) deficient females by an inexpensive cytochemical G6PD staining method that is easy to perform, allowing diagnosis of G6PD deficiency without cumbersome genetic analysis. Three subject groups were included in the study. The first group consisted of 15 hemizygous deficient males. The second and the third group were composed of 15 heterozygous deficient females and 15 healthy individuals, respectively. Biochemical determination and cytochemical staining of G6PD activity were performed in samples of all subjects. Results obtained with the cytochemical staining method correlated significantly with the biochemical data (p < 0.001), but a only 51-68% of the erythrocytes were stained positively in females with normal biochemical G6PD activity despite their having a G6PD-deficient child. This observation clearly indicates that these individuals are heterozygously deficient. These findings show that the cytochemical staining method to detect G6PD activity in erythrocytes is reliable, sensitive and specific and is superior to the biochemical method. Therefore, this method can be used routinely to detect heterozygous G6PD deficiency.

O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

PubMed

Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

2017-07-01

Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women.

PubMed

da Silva, Vanessa R; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A; Midttun, Øivind; Quinlivan, Eoin P; Garrett, Timothy J; Coats, Bonnie; Shankar, Meena N; Percival, Susan S; Chi, Yueh-Yun; Muller, Keith E; Ueland, Per Magne; Stacpoole, Peter W; Gregory, Jesse F

2013-11-01

Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (<0.35 mg/d). liquid chromatography-tandem mass spectrometry analysis of the compounds relevant to one-carbon metabolism showed that vitamin B-6 restriction yielded increased cystathionine (53% pre- and 76% postprandial; P < 0.0001) and serine (12% preprandial; P < 0.05), and lower creatine (40% pre- and postprandial; P < 0.0001), creatinine (9% postprandial; P < 0.05), and dimethylglycine (16% postprandial; P < 0.05) relative to the vitamin B-6-adequate state. In the tryptophan pathway, vitamin B-6 restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P < 0.01) and higher 3-hydroxykynurenine (39% pre- and 34% postprandial; P < 0.01). Multivariate ANOVA analysis showed a significant global effect of vitamin B-6 restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency.

[Vitamin D status in 6- to 10-year-old children: a French multicenter study in 326 children].

PubMed

Mallet, E; Gaudelus, J; Reinert, P; Stagnara, J; Bénichou, J; Basuyau, J-P; Maurin, M; Cordero, J; Roden, A; Uhlrich, J

2014-10-01

To assess the vitamin D status of children aged 6-10years in the French general population for whom no guidelines have yet been defined due to insufficient data. The study was conducted during two winters with very different sunshine levels: 5 March to 17 April 2012 and 8 January to 16 April 2013 in 20 then 22 centers. Three hundred children (60 children for each year of age) attending an ambulatory care unit or outpatient department for a reason unrelated to vitamin D status were included at the end of winter in 20 hospital centers (ten centers in the northern half of France above latitude 46-47°N/Lille: 50°N and ten centers in the southern half of France below latitude 46-47°N/Marseille: 43°N). Centralized 25 hydroxyvitamin D (25(OH)D), alkaline phosphatase (ALP), and parathormone (PTH) assays were performed on leftover blood samples. The currently accepted normal range for 25(OH)D was used to define the following categories: ≤25nmol/L: severe vitamin D deficiency, 25nmol/L100nmol/L: high vitamin D status. A standardized questionnaire was used to collect the child's characteristics, use of a vitamin D supplement, and milk and dairy product intake. The cumulative number of hours of sunshine over the 90days prior to inclusion in each center was obtained from the Météo-France weather bureau. 25(OH)D assays were performed in 326 children; more than 95% of children received milk and dairy products and 38% had received a vitamin D supplement since starting the school year: 3.1% of children in the overall population presented severe vitamin D deficiency, 34.4% presented vitamin D deficiency, 53.1% had a sufficient vitamin D status, and 9.5% had a 25(OH)D concentration >100nmol/L with no impact on serum calcium and urinary calcium. Children living in the north of France generally had lower 25(OH)D levels than children living in the south of France. In the non

Is zinc deficiency a risk factor for atherosclerosis?

PubMed

Beattie, John H; Kwun, In-Sook

2004-02-01

The development of atherosclerosis is influenced by genetic, lifestyle and nutritional risk factors. Zn and metallothionein deficiency can enhance oxidative-stress-related signalling processes in endothelial cells, and since changes in available plasma Zn may affect the Zn status of the endothelium, Zn deficiency could be a risk factor for IHD. Although the association of Zn with many proteins is essential for their function, three key signalling processes are highlighted as being principal targets for the effect of Zn deficiency: the activation of NF-kappaB, the activation of caspase enzymes and the signalling of NO. The need to develop a reliable indicator of Zn status is critical to any epidemiological approach for studying the relationship between Zn status and disease incidence. Studies using appropriate animal models and investigating how the plasma Zn pool influences endothelial intracellular labile Zn would be helpful in appreciating the importance of Zn deficiency in atherogenesis.

Sirtuin-6 deficiency exacerbates diabetes induced impairment of wound healing

PubMed Central

Thandavarayan, Rajarajan A; Garikipati, Venkata Naga Srikanth; Joladarashi, Darukeshwara; Babu, Sahana Suresh; Jeyabal, Prince; Verma, Suresh K; Mackie, Alexander R; Khan, Mohsin; Arumugam, Somasundaram; Watanabe, Kenichi; Kishore, Raj; Krishnamurthy, Prasanna

2015-01-01

Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyze the role of SIRT6 in cutaneous wound healing, paired 6 mm stented wound were created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and non-sensed siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6-siRNA treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31 staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor (VEGF) expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor kB (NF-kB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α and interleukin-1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF-kB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that activation of SIRT6 signaling might be a potential therapeutic approach for promoting wound healing in diabetics. PMID:26010430

Prevalence and molecular characterization of glucose-6-phosphate dehydrogenase deficiency in northern Thailand.

PubMed

Charoenkwan, Pimlak; Tantiprabha, Watcharee; Sirichotiyakul, Supatra; Phusua, Arunee; Sanguansermsri, Torpong

2014-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited enzymopathies in endemic areas of malaria including Southeast Asia. The molecular features of G6PD deficiency are similar among Southeast Asian population, with differences in the type of the prominent variants in each region. This study determined the prevalence and molecular characteristics of G6PD deficiency in northern Thailand. Quantitative assay of G6PD activity was conducted in 566 neonatal cord blood samples and 6 common G6PD mutations were determined by PCR-restriction fragment length polymorphism method on G6PD complete and intermediate deficiency samples. Ninety newborns had G6PD deficiency, with prevalence in male newborns of 17% and that of female newborns having an intermediate and complete deficiency of 13% and 2%, respectively. From 95 G6PD alleles tested, G6PD Mahidol, G6PD Kaiping, G6PD Canton, G6PD Viangchan, G6PD Union, and G6PD Chinese-5 was detected in 19, 17, 15, 13, 7, and 2 alleles, respectively. Our study shows that the prevalence of G6PD deficiency in northern Thai population is high and combination of the common Chinese mutations is the majority, a distribution different from central and southern Thailand where G6PD Viangchan is the prominent variant. These findings suggest a higher proportion of assimilated Chinese ethnic group in the northern Thai population.

Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence

PubMed Central

Kwok, Man Ki; Leung, Gabriel M.; Schooling, C. Mary

2016-01-01

Background To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported. Methods In a population-representative Chinese birth cohort: “Children of 1997” (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting. Results Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence. Conclusions G6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation. PMID:27824927

Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence.

PubMed

Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

2016-01-01

To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported. In a population-representative Chinese birth cohort: "Children of 1997" (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting. Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence. G6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation.

SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES.

PubMed

Silva, Rafaella de Andrade; Malta, Flávia Monteiro França; Correia, Maria Flora Ferreira Sampaio Carvalho; Burgos, Maria Goretti Pessoa de Araújo

Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the São João Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (p<0.05). Among 286 individuals evaluated, females accounted for 90.9% of the overall sample (both techniques). Gastric banding was performed more (68.9%), but greater nutrient deficiencies were found following gastric bypass. Iron was the most prevalent deficiency (21.3%), followed by vitamin B12 (16.9%) and folic acid (4.5%). Mild to moderate alcohol intake, adherence to the diet and the use of multivitamins reduced the frequency, but did not avoid micronutrient deficiency. Vitamin B12, iron and folic acid deficiencies were found in the first and second year following the two bariatric techniques analyzed and were more frequent among individuals submitted to gastric bypass. As diferentes técnicas da cirurgia da obesidade combinam má absorção com procedimentos restritivos e podem levar à complicações metabólicas, entre as quais se destacam as deficiências de micronutrientes. Avaliar a deficiência de vitamina B12, ferro e ácido fólico e fatores associados ao estilo de vida de obesos submetidos a diferentes técnicas cirúrgicas. Análise retrospectiva dos prontuários eletrônicos de pacientes submetidos à cirurgia bariátrica pelas t

Supplemental levels of iron and calcium interfere with repletion of zinc status in zinc-deficient animals.

PubMed

Jayalakshmi, S; Platel, Kalpana

2016-05-18

Negative interactions between minerals interfering with each other's absorption are of concern when iron and calcium supplements are given to pregnant women and children. We have previously reported that supplemental levels of iron and calcium inhibit the bioaccessibility of zinc, and compromise zinc status in rats fed diets with high levels of these two minerals. The present study examined the effect of supplemental levels of iron and calcium on the recovery of zinc status during a zinc repletion period in rats rendered zinc-deficient. Iron and calcium, both individually and in combination, significantly interfered with the recovery of zinc status in zinc deficient rats during repletion with normal levels of zinc in the diet. Rats maintained on diets containing supplemental levels of these two minerals had significantly lower body weight, and the concentration of zinc in serum and organs was significantly lower than in zinc-deficient rats not receiving the supplements. Iron and calcium supplementation also significantly inhibited the activity of zinc-containing enzymes in the serum as well as liver. Both iron and calcium independently exerted this negative effect on zinc status, while their combination seemed to have a more prominent effect, especially on the activities of zinc containing enzymes. This investigation is probably the first systematic study on the effect of these two minerals on the zinc status of zinc deficient animals and their recovery during repletion with normal amounts of zinc.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso.

PubMed

Ouattara, Abdoul Karim; Bisseye, Cyrille; Bazie, Bapio Valery Jean Télesphore Elvira; Diarra, Birama; Compaore, Tegwindé Rebeca; Djigma, Florencia; Pietra, Virginio; Moret, Remy; Simpore, Jacques

2014-08-01

To investigate 4 combinations of mutations responsible for glucose-6-phosphate dehydrogenase (G6PD) deficiency in a rural community of Burkina Faso, a malaria endemic country. Two hundred individuals in a rural community were genotyped for the mutations A376G, G202A, A542T, G680T and T968C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism. The prevalence of the G6PD deficiency was 9.5% in the study population. It was significantly higher in men compared to women (14.3% vs 6.0%, P=0.049). The 202A/376G G6PD A- was the only deficient variant detected. Plasmodium falciparum asymptomatic parasitaemia was significantly higher among the G6PD-non-deficient persons compared to the G6PD-deficient (P<0.001). The asymptomatic parasitaemia was also significantly higher among G6PD non-deficient compared to G6PD-heterozygous females (P<0.001). This study showed that the G6PD A- variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.

Nutritional Status Prior to Laparoscopic Sleeve Gastrectomy Surgery.

PubMed

Sherf Dagan, Shiri; Zelber-Sagi, Shira; Webb, Muriel; Keidar, Andrei; Raziel, Asnat; Sakran, Nasser; Goitein, David; Shibolet, Oren

2016-09-01

Two main causes for nutrient deficiencies following bariatric surgery (BS) are pre-operative deficiencies and favoring foods with high-energy density and poor micronutrient content. The aims of this study were to evaluate nutritional status and gender differences and the prevalence of nutritional deficiencies among candidates for laparoscopic sleeve gastrectomy (LSG) surgery. A cross-sectional analysis of pre-surgery data collected as part of a randomized clinical trial on 100 morbidly obese patients with non-alcoholic fatty liver disease (NAFLD) admitted to LSG surgery at Assuta Medical Center between February 2014 and January 2015. Anthropometrics, food intake, and fasting blood tests were evaluated during the baseline visit. One-hundred patients completed the pre-operative measurements (60 % female) with a mean age of 41.9 ± 9.8 years and a mean BMI of 42.3 ± 4.7 kg/m(2). Pre-operatively, deficiencies for iron, ferritin, folic acid, vitamin B1, vitamin B12, vitamin D, and hemoglobin were 6, 1, 1, 6, 0, 22, and 6 %, respectively. Pre-surgery, mean energy, protein, fat, and carbohydrate intake were 2710.7 ± 1275.7 kcal/day, 114.2 ± 48.5, 110.6 ± 54.5, and 321.6 ± 176.1 gr/day, respectively. The intakes for iron, calcium, folic acid, vitamin B12, and vitamin B1 were below the Dietary Reference Intake (DRI) recommendations for 46, 48, 58, 14, and 34 % of the study population, respectively. We found a low prevalence of nutritional deficiencies pre-operatively except for vitamin D. Most micronutrient intake did not reach the DRI recommendations, despite high-caloric and macronutrient intake indicating a poor dietary quality.

[Glucose-6-phosphate dehydrogenase deficiency in children: a case report].

PubMed

Verdugo L, Patricia; Calvanese T, Marlene; Rodríguez V, Diego; Cárcamo C, Cassandra

2014-02-01

Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. To analyze the case of a child who presented hemolytic crisis due to favism. A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

PubMed

Boonyuen, Usa; Chamchoy, Kamonwan; Swangsri, Thitiluck; Junkree, Thanyaphorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika

2017-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants-G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton+Bangkok noi, and G6PD Union+Viangchan. G6PD Bangkok and G6PD Canton+Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union+Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union+Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Glucose-6-phosphate dehydrogenase deficiency: disadvantages and possible benefits.

PubMed

Manganelli, Genesia; Masullo, Ugo; Passarelli, Stefania; Filosa, Stefania

2013-03-01

We review here some recent data about Glucose-6-phosphate dehydrogenase (G6PD), the housekeeping X-linked gene encoding the first enzyme of the pentose phosphate pathway (PPP), a NADPH-producing dehydrogenase. This enzyme has been popular among clinicians, biochemists, geneticists and molecular biologists because it is the most common form of red blood cell enzymopathy. G6PD deficient erythrocytes do not generate NADPH in any other way than through the PPP and for this reason they are more susceptible than any other cells to oxidative damage. Moreover, this enzyme has also been of crucial importance in many significant discoveries; indeed, G6PD polymorphisms have been instrumental in studying X-inactivation in the human species, as well as in establishing the clonal nature of certain tumors. G6PD deficiency, generally considered as a mild and benign condition, is significantly disadvantageous in certain environmental conditions like in presence of certain drugs. Nevertheless, G6PD deficiency has been positively selected by malaria, and recent knowledge seems to show that it also confers an advantage against the development of cancer, reduces the risk of coronary diseases and has a beneficial effect in terms of longevity.

G6PD deficiency at Sumba in Eastern Indonesia is prevalent, diverse and severe: implications for primaquine therapy against relapsing Vivax malaria.

PubMed

Satyagraha, Ari Winasti; Sadhewa, Arkasha; Baramuli, Vanessa; Elvira, Rosalie; Ridenour, Chase; Elyazar, Iqbal; Noviyanti, Rintis; Coutrier, Farah Novita; Harahap, Alida Roswita; Baird, J Kevin

2015-03-01

Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm.

G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria

PubMed Central

Satyagraha, Ari Winasti; Sadhewa, Arkasha; Baramuli, Vanessa; Elvira, Rosalie; Ridenour, Chase; Elyazar, Iqbal; Noviyanti, Rintis; Coutrier, Farah Novita; Harahap, Alida Roswita; Baird, J. Kevin

2015-01-01

Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm. PMID:25746733

Foods contributing to vitamin B6, folate, and vitamin B12 intakes and biomarkers status in European adolescents: The HELENA study.

PubMed

Iglesia, Iris; Mouratidou, Theodora; González-Gross, Marcela; Huybrechts, Inge; Breidenassel, Christina; Santabárbara, Javier; Díaz, Ligia-Esperanza; Hällström, Lena; De Henauw, Stefaan; Gottrand, Frédéric; Kafatos, Anthony; Widhalm, Kurt; Manios, Yannis; Molnar, Denes; Stehle, Peter; Moreno, Luis A

2017-06-01

To examine the association between food groups consumption and vitamin B 6 , folate and B 12 intakes and biomarkers in adolescents. In total 2189 individuals participating in the cross-sectional Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for analysis of dietary intakes (46 % males) and 632 for biomarker analysis (47 % males). Food intakes were assessed by two non-consecutive 24-h recalls. Biomarkers were measured by chromatography and immunoassay. Food groups which best discriminated participants in the extreme tertiles of the distribution of vitamins were identified by discriminant analyses. Food groups with standardised canonical coefficients higher or equal to 0.3 were selected as valid discriminators of vitamins intake and biomarkers extreme tertiles. Linear mixed model elucidated the association between food groups and vitamins intakes and biomarkers. Vitamin B 6 intakes and biomarkers were best discriminated by meat (males and females), margarine and mixed origin lipids only in males and breakfast cereals (females). Breakfast cereals (males), and fruits, margarine and mixed origin lipids, vegetables excluding potatoes, breakfast cereals, and soups/bouillon (females) determined the most folate intakes and biomarkers. Considering vitamin B 12 intakes and biomarkers, meat, and white and butter milk (males and females), snacks (males), and dairy products (females) best discriminated individual in the extremes of the distribution. Fewer associations were obtained with mixed model for biomarkers than for vitamins intakes with food groups. Whereas B-vitamin intakes were associated with their food sources, biomarkers did with overall food consumption. Low-nutrient-density foods may compromise adolescents' vitamin status.

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

Micronutrient Status and Nutritional Intake in 0- to 2-Year-old Children Consuming a Cows' Milk Exclusion Diet.

PubMed

Kvammen, Janne A; Thomassen, Rut A; Eskerud, Mari B; Rugtveit, Jarle; Henriksen, Christine

2018-05-01

To study micronutrient status and nutritional intake from complementary feeding in children on a cows' milk exclusion (CME) diet. Fifty-seven children with cows' milk allergy, younger than 2 years, were included in a cross-sectional study. Blood was analyzed for micronutrient status. Complementary feeding was defined as all solids and liquids except of breast milk, and assessed by 3-day food diary. The results were analyzed according to 3 feeding patterns: mainly breast-fed (mBF), partially breast-fed, and no breast milk group (nBM). The children had a median age of 9 months and micronutrient status was within normal range for total homocysteine (p-tHcy), s-B12, s-folate, b-Hb, s-ferritin, s-zinc, and s-25(OH)D. There were no significant differences between feedings groups, except for B12-biomarkers. The mBF had higher p-tHcy (P < 0.000) and lower s-B12 (P = 0.002) compared nBM. Vitamin B12 deficiency (p-tHcy >6.5 μmol/L combined with s-B12 <250 pmol/L) was found in 12% of participants, most frequently among the mBF (36%) and none in nBM group (P = 0.009). Vitamin B12 intake from complementary feeding was negatively correlated with p-tHcy (r = -0.479, P = 0.001) and positively with s-B12 (r = 0.410, P = 0.003). Iron deficiency anemia was found in 5%. Iron intake correlated positively with b-Hb (r = 0.324, P = 0.02). Zinc deficiency was found in 7% and low 25(OH)D in 9%. Vitamin D intake was positively correlated with the use of supplements (r = 0.456, P = 0.001). The risk of B12 deficiency was high in mBF infants on CME diet, and complementary feeding was associated with better B12 status. Iron, zinc, and vitamin D deficiencies were present in all feeding groups. Complementary feeding should be introduced at 4 to 6 months of age. Vitamin D supplement is recommended to ensure adequate intake.

Metabolite Profile Analysis Reveals Functional Effects of 28-Day Vitamin B-6 Restriction on One-Carbon Metabolism and Tryptophan Catabolic Pathways in Healthy Men and Women123

PubMed Central

da Silva, Vanessa R.; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A.; Midttun, Øivind; Quinlivan, Eoin P.; Garrett, Timothy J.; Coats, Bonnie; Shankar, Meena N.; Percival, Susan S.; Chi, Yueh-Yun; Muller, Keith E.; Ueland, Per Magne; Stacpoole, Peter W.; Gregory, Jesse F.

2013-01-01

Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5′-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (<0.35 mg/d). liquid chromatography-tandem mass spectrometry analysis of the compounds relevant to one-carbon metabolism showed that vitamin B-6 restriction yielded increased cystathionine (53% pre- and 76% postprandial; P < 0.0001) and serine (12% preprandial; P < 0.05), and lower creatine (40% pre- and postprandial; P < 0.0001), creatinine (9% postprandial; P < 0.05), and dimethylglycine (16% postprandial; P < 0.05) relative to the vitamin B-6–adequate state. In the tryptophan pathway, vitamin B-6 restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P < 0.01) and higher 3-hydroxykynurenine (39% pre- and 34% postprandial; P < 0.01). Multivariate ANOVA analysis showed a significant global effect of vitamin B-6 restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency. PMID:23966327

Vitamin B1 Deficiency Does not Affect the Liver Concentrations of the Other Seven Kinds of B-Group Vitamins in Rats

PubMed Central

Shibata, Katsumi; Shimizu, Atsushi; Fukuwatari, Tsutomu

2013-01-01

We aimed to determine the effects of vitamin B1 deficiency on vitamin contents of urine, liver, and blood. In the current study, rats were divided into 3 groups (n = 5, each group): the first was freely fed a complete diet (ad lib-fed control group); the second freely fed a vitamin B1-free diet (vitamin B1 deficient group); and the third pair-fed a complete diet with the same amounts of the vitamin B1 deficient group (pair-fed control group). The experimental period was for 15 days. The blood concentrations of vitamin B2, PLP, vitamin B12, folic acid, and biotin were lower in the pair-fed control than in the ad lib-fed control and those of nicotinamide and pantothenic acid were the same. We conclude that Vitamin B1 deficiency did not affect concentrations of the other B-group vitamins. PMID:23935367

Glucose-6-phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experıence.

PubMed

Celik, H Tolga; Günbey, Ceren; Unal, Sule; Gümrük, Fatma; Yurdakök, Murat

2013-05-01

The aim of this study was to investigate the prevalence of glucose-6-phospate dehydrogenase (G6PD) deficiency in newborn infants with neonatal hyperbilirubinaemia and to compare the clinical features of G6PD-deficient and G6PD-normal newborn infants. A total of 4906 term and preterm neonates with indirect hyperbilirubinaemia were retrospectively evaluated according to demographic, neonatal features, bilirubin levels, erythrocyte G6PD levels, other risk factors and treatments. Among 4906 newborn infants with indirect hyperbilirubinaemia, 55 (1.12%) neonates were G6PD-deficient. In our study, no statistically significant difference was detected between G6PD-deficient and G6PD-normal infants in relation to the time of onset of jaundice, bilirubin levels and duration of phototherapy. However, the incidence of exchange transfusion in G6PD-deficient infants was 16.4% while it was only 3.3% in G6PD normal infants (P < 0.05). Testing for G6PD must be ordered to all newborns who are receiving phototherapy and especially to those who are coming from the high incident geographical regions and less responsive to phototherapy. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

[Glucose-6-phosphate dehydrogenase deficiency: report of 2 cases].

PubMed

Garassini, M E; Alvarado, M; Garassini, M A

1994-01-01

Glucose 6 phosphate dehydrogenase (G6PD) is an enzyme related to the metabolism of glutation, an antioxidant agent. Its deficiency causes hemolisis, generally well tolerated. However there are some factors including, exercise, infections and oxidants drugs that stimulate the hemolisis of the older red blood cells. We report two patients with G6PD deficiency, that were initially diagnosed as acute viral hepatitis. Although this pathology is not frequent it should be recognized, for the implication of giving profilactic antimalaric drugs in endemic areas. The diagnosis should be suspected in patients with unconjugated jaundice, always investigating the previous ingestion of oxidants drugs.

Increased erythrocyte deformability in fetal erythropoiesis and in erythrocytes deficient in glucose-6-phosphate dehydrogenase and other glycolytic enzymes.

PubMed

Johnson, R M; Panchoosingh, H; Goyette, G; Ravindranath, Y

1999-01-01

Erythrocyte deformability was determined in more than 500 clinical samples, and was found to be elevated in conditions in which fetal-like red cells are produced: aplastic anemia (3/3 cases), myelodysplastic syndromes, polycythemias, sickle cell anemia during treatment with hydroxyurea, paroxysmal nocturnal hemoglobinuria, and recovery from B12 deficiency. Elevated deformability was observed in neonatal erythrocytes, and during recovery from transient erythroblastopenia of childhood, when fetal-like red cells are known to be produced. Increased deformability appears to be a feature of fetal and fetal-like red cells. Forty-eight cases of enzymatically verified glucose-6-phosphate (G-6-PD) deficiency were also examined. Thirty out of 32 G-6-PD(A-) individuals, including both heterozygotes and hemizygotes, exhibited increased deformability during the steady state. In contrast, G-6-PD(Med) hemizygotes had normal deformability. Increased deformability was also found in G-6-PD(Huron) (n=3), G-6-PD(Wayne) (n=4), triose phosphate isomerase deficiency (n=2), and pyruvate kinase deficiency (n=2). An elevated osmoscan was found in more than 90% of female G-6-PD heterozygotes, affording a simple screening test for heterozygotes. Deformability remained high during hemolytic episodes, when older enzyme deficient cells are removed from the circulation. In four cases of G-6-PD deficiency with normal deformability, evidence for co-existing hereditary spherocytosis was found. The combination of conditions with opposing effects on deformability resulted in nearly normal deformability. Because increased red cell deformability is a feature of fetal erythrocytes, these results suggest that the red cells in many cases of glycolytic enzyme deficiency are fetal-like.

Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland.

PubMed

Schüpbach, R; Wegmüller, R; Berguerand, C; Bui, M; Herter-Aeberli, I

2017-02-01

Vegetarian and vegan diets have gained popularity in Switzerland. The nutritional status of individuals who have adopted such diets, however, has not been investigated. The aim of this study was to assess the intake and status of selected vitamins and minerals among vegetarian and vegan adults living in Switzerland. Healthy adults [omnivores (OVs), n OV  = 100; vegetarians (VGs), n VG  = 53; vegans (VNs), n VN  = 53] aged 18-50 years were recruited, and their weight and height were measured. Plasma concentrations of the vitamins A, C, E, B1, B2, B6, B12, folic acid, pantothenic acid, niacin, biotin and β-carotene and of the minerals Fe, Mg and Zn and urinary iodine concentration were determined. Dietary intake was assessed using a three-day weighed food record, and questionnaires were issued in order to assess the physical activity and lifestyle of the subjects. Omnivores had the lowest intake of Mg, vitamin C, vitamin E, niacin and folic acid. Vegans reported low intakes of Ca and a marginal consumption of the vitamins D and B12. The highest prevalence for vitamin and mineral deficiencies in each group was as follows: in the omnivorous group, for folic acid (58 %); in the vegetarian group, for vitamin B6 and niacin (58 and 34 %, respectively); and in the vegan group, for Zn (47 %). Despite negligible dietary vitamin B12 intake in the vegan group, deficiency of this particular vitamin was low in all groups thanks to widespread use of supplements. Prevalence of Fe deficiency was comparable across all diet groups. Despite substantial differences in intake and deficiency between groups, our results indicate that by consuming a well-balanced diet including supplements or fortified products, all three types of diet can potentially fulfill requirements for vitamin and mineral consumption.

Prevalence of G6PD deficiency and Plasmodium falciparum parasites in asymptomatic school children living in southern Ghana.

PubMed

Amoah, Linda Eva; Opong, Akua; Ayanful-Torgby, Ruth; Abankwa, Joana; Acquah, Festus K

2016-07-26

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. Although G6PD deficiency is globally distributed it is more prevalent in malaria-endemic countries. Several mutations have been identified in the G6PD gene, which alter enzyme activity. The G6PD genotype predominantly found in sub-Saharan Africa is the G6PDB (G6PD376A) with (G6PD376G) and G6PDA- (G6PD376G/202A, G6PD376G/542T, G6PD376G/680T and G6PD376G/968C) occurring at lower frequencies. The aim of this study was to identify the prevalence of G6PD deficiency and asymptomatic Plasmodium falciparum carriage in children living in southern Ghana and determine whether G6PD deficiency influences asymptomatic carriage of P. falciparum parasites. Blood samples were obtained once a month from 170 healthy Ghanaian school children aged between 5 and 12 years from Basic schools in two communities Obom and Abura with similar rainfall patterns and malaria peak seasons. G6PD enzyme activity was assessed using the qualitative G6PD RDT kit (AccessBIO). G6PD genotyping and asymptomatic parasite carriage was determined by PCR followed by restriction fragment length polymorphism (RFLP) of DNA extracted from dried blood spots. The only sub-Saharan G6PD A- allele detected was the A376G/G202A found in 12.4 % (21/170), of the children and distributed as 4.1 % (7/170) A-, 1.8 % (3/170) A-/A- homozygous deficient males and females and 6.5 % (11/170) A/A- and B/A- heterozygous deficient females. Phenotypically, 10.6 % (15/142) of the children were G6PD deficient. The asymptomatic carriage of P. falciparum by PCR was 50, 29.4, 38.2 and 38.8 % over the months of February through May 2015, respectively, and 28.8, 22.4, 25.9 and 5.9 % by microscopy during the same periods. G6PD deficiency was significantly associated with a lowered risk of PCR-estimated asymptomatic P. falciparum carriage in children during the off peak malaria season in Southern Ghana.

Minimum Selenium Requirements Increase When Repleting Second-Generation Selenium-Deficient Rats but Are Not Further Altered by Vitamin E Deficiency.

PubMed

Sunde, Roger A; Thompson, Kevin M; Fritsche, Kevin L; Evenson, Jacqueline K

2017-05-01

Second-generation selenium-deficient weanling rats fed graded levels of dietary Se were used (a) to study the impact of initial Se deficiency on dietary Se requirements; (b) to determine if further decreases in selenoperoxidase expression, especially glutathione peroxidase 4 (Gpx4), affect growth or gross disease; and (c) to examine the impact of vitamin E deficiency on biochemical and molecular biomarkers of Se status. Rats were fed a vitamin E-deficient and Se-deficient crystalline amino acid diet (3 ng Se/g diet) or that diet supplemented with 100 μg/g all-rac-α-tocopheryl acetate and/or 0, 0.02, 0.05, 0.075, 0.1, or 0.2 μg Se/g diet as Na 2 SeO 3 for 28 days. Se-supplemented rats grew 6.91 g/day as compared to 2.17 and 3.87 g/day for vitamin E-deficient/Se-deficient and vitamin E-supplemented/Se-deficient groups, respectively. In Se-deficient rats, liver Se, plasma Gpx3, red blood cell Gpx1, liver Gpx1 and Gpx4 activities, and liver Gpx1 mRNA levels decreased to <1, <1, 21, 1.6, 49, and 11 %, respectively, of levels in rats fed 0.2 μg Se/g diet. For all biomarkers, ANOVA indicated significant effects of dietary Se, but no significant effects of vitamin E or vitamin E × Se interaction, showing that vitamin E deficiency, even in severely Se-deficient rat pups, does not result in compensatory changes in these biochemical and molecular biomarkers of selenoprotein expression. Se requirements determined in this study, however, were >50 % higher than in previous studies that started with Se-adequate rats, demonstrating that dietary Se requirements determined using initially Se-deficient animals can result in overestimation of Se requirements.

[Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status].

PubMed

López-Alarcón, Mardia; Chávez-Negrete, Adolfo; Montalvo-Velarde, Irene; Maldonado-Hernández, Jorge; Vital-Reyes, Víctor Saúl

2011-01-01

Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.

Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

PubMed

Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

1996-10-15

IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

[Severe vitamin D deficiency in children from Punta Arenas, Chile: Influence of nutritional status on the response to supplementation].

PubMed

Brinkmann, Karin; Le Roy, Catalina; Iñiguez, Germán; Borzutzky, Arturo

2015-01-01

There is a high risk of vitamin D (VD) deficiency in the population of southern Chile that can be treated with VD supplements. Weight excess (WE) can influence the response to supplements. To study the prevalence of VD deficiency and the effect of cholecalciferol (VD3) supplements in healthy children from Punta Arenas, Chile, and evaluate a possible association with nutritional status. Demographic and anthropometric data, as well as laboratory assessment of serum 25-hidroxyvitamin D (25OHD) and other bone metabolism parameters were evaluated. After baseline evaluation, children were supplemented with VD3 1600 IU/day for one month, after which 25OHD was retested. Of the 108 children studied, 50% were boys, and had a mean age of 9.6±0.5 years. Nutritional assessment showed that 39% had normal weight, 46% were overweight, and 15% were obese. Median 25OHD was 10.9ng/ml: 96.3% had deficiency (<20ng/ml) and 3.7% insufficiency (20-29ng/ml). Severe deficiency was found in 62% (<12ng/ml). Baseline 25OHD was not affected by nutritional status. After supplementation, median 25OHD was 17.5ng/ml: 62% had deficiency, 36% insufficiency, and 2% sufficiency (>30ng/ml). Children with WE had a significantly lower increase in 25OHD than children with normal weight (5±5.5 vs. 7.7±4.9, p=03). Children with WE may require 32% higher VD dose than normal weight children to attain the same 25OHD concentration. Chilean schoolchildren from Punta Arenas have high prevalence of WE and VD deficiency, with a majority in the range of severe VD deficiency. WE interferes in the response to VD supplementation, leading to a lower increase in 25OHD. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Drug-induced glucose-6-phosphate dehydrogenase deficiency-related hemolysis risk assessment.

PubMed

Yang, Yang; Li, Zuofeng; Nan, Peng; Zhang, Xiaoyan

2011-06-01

Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects human red blood cells from premature destruction caused by oxidative damage. People suffering from G6PD deficiency would be vulnerable to various oxidative substances, such as fava beans and oxidant drugs. Until now, many institutes, organizations or domain experts have compiled low-risk or high-risk drugs collection for patients with G6PD deficiency, mainly from the case report or clinical trails. Recently, we have explored a classification system to predict drug-induced hemolytic potential. In this paper, we screen the normally used over-the-counter (OTC) drugs for "high-risk" and "low-risk" ones to G6PD deficient patients by this system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Correlation between serum levels of vitamin B12 and anti-Helicobacter pylori IgA antibodies in vitamin B12 deficient Palestinian patients.

PubMed

Abu Hilu, Rasmi; Dudeen, Osama; Barghouthi, Sameer Abdullatif

2015-01-01

H. pylori infection and vitamin B12 (vB12) deficiency have high prevalence rates among Palestinians. It was observed that most people who suffered from vB12 deficiency were positive for H. pylori. The correlation between H. pylori infection and vB12 deficiency was investigated in a representative segment of the Palestinian population. ELISA was used to determine levels of vitamin B12 (vB12) and anti-H. pylori IgA in sera from 238 participants from Al-Khalil district (Hebron), Palestine. There was a strong negative Pearson's correlation coefficient (r = -0.45; P = 0.00001) between levels of anti-H. pylori IgA and vB12 levels in sera drawn from 238 participants (133 patients and 105 control subjects). Two important contaminating variables were identified in this study: healthy control subjects with elevated anti-H. pylori IgA titers and vB12-deficient patients testing negative for anti-H. pylori IgA antibodies. The exclusion of the sources of contamination resulted in a stronger negative correlation; r = -0.58 (P = 0.00001). The study provided a good screening system that may predict vB12 deficiency before its actual manifestation. If not treated, asymptomatic subjects showing increased anti-H.pylori IgA titers (> 15 NTU/mL) are likely to be at risk of developing vB12 deficiency.