Science.gov

Sample records for myoglobinuria

  1. Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria

    SciTech Connect

    Martin-du Pan, R.C.; Favre, H.; Junod, A.

    1997-04-14

    We report on a Swiss family in which 10 individuals of both sexes in 4 successive generations suffered from myoglobinuria, precipitated by febrile illness. It is the second family described with autosomal dominant inheritance of myoglobinuria. Four individuals suffered acute renal failure, which in two was reversible only after dialysis. In a recent case, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy, associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in the mitochondrial DNA was identified. Along with the inheritance pattern, these findings suggest that the myoglobinuria in this family is caused by a nuclear-encoded mutation affecting the respiratory chain. 22 refs., 2 figs.

  2. Myoglobinuria with acute renal failure and hot kidneys seen on bone imaging

    SciTech Connect

    Sheth, K.J.; Sty, J.R.; Johnson, F.; Tisdale, P.

    1984-09-01

    We report a case of myoglobinuria secondary to prolonged seizures. The child showed ''hot kidneys'' with bone scintigraphy. The disease entity and etiologies of nontraumatic rhabdomyolysis are discussed.

  3. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

    PubMed

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M; Pines, Ophry; Elpeleg, Orly

    2008-10-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy. PMID:18817903

  4. Exercise-induced cramp, myoglobinuria, and tubular aggregates in phosphoglycerate mutase deficiency.

    PubMed

    Oh, Shin J; Park, Kyung-Seok; Ryan, Hewitt F; Danon, Moris J; Lu, Jiesheng; Naini, Ali B; DiMauro, Salvatore

    2006-11-01

    We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise-induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests produced subnormal increases of venous lactate. Muscle biopsies showed subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were markedly decreased (3% of the normal mean) and molecular genetic studies showed that both patients were homozygous for a described missense mutation (W78X). A review of 15 cases with tubular aggregates in the muscle biopsies from our laboratory and 15 cases with PGAM deficiency described in the literature showed that this clinicopathological triad is highly suggestive of PGAM deficiency. PMID:16881065

  5. [Extra-cardial rise of the CPK in the screening of urgent diagnostic (among others, a case of anaesthesia induced myoglobinuria and a case of malignant hypertermia) (author's transl)].

    PubMed

    Bernhardt, D; Hörder, M H

    1977-11-18

    Tests are being carried out on 37 patients and healthy volunteers, to differentiate the various, from heart independent, creatin-phosphokinase (CPK) increases, in order to recognize anaesthesia-endangered patients. A rise of the serum-CPK-level, dependent on trauma is insignificant for the anaesthesia. A significant rise of the CPK during a gener al anaesthesia and particularly extreme high values after 24 hours, (example, more than 10 000 U/l) is reason to think of a course of a malignant hyperthermia or myoglobinuria in a subclinical form. Relatives of hyperthermia- or myoglobinuria suspected families are in all cases anaesthesia-endangered, even with a very small rise of CPK-values. The knowledge of these connections is highly important also for internal medical spheres. PMID:927298

  6. Myoglobinuria and Skeletal Muscle Phosphorylase Deficiency

    PubMed Central

    Nixon, J. C.; Hobbs, W. K.; Greenblatt, J.

    1966-01-01

    Investigation of a patient complaining of exercise-induced dark urine, pain, stiffness and tenderness of skeletal muscle revealed findings characteristic of McArdle's disease. The dark urine was attributable to the excretion of myoglobin, and an ischemic exercise test failed to demonstrate the usual rise and fall in blood lactate and pyruvate. Enzyme assays of skeletal muscle showed an absence of phosphorylase, a slight increase in phosphorylase b kinase and a slight decrease in phosphoglucomutase. Chemical and histochemical analyses demonstrated an increase in the skeletal muscle glycogen content and an enlargement of the muscle cells. No abnormality of liver glycogen metabolism was found. In the absence of specific therapy, an effective and practical form of treatment is reduction of exercise below the threshold of symptoms. ImagesFig. 1Fig. 2Fig. 6Fig. 7Fig. 8 PMID:4952390

  7. Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency.

    PubMed

    Coppens, Sandra; Koralkova, Pavla; Aeby, Alec; Mojzikova, Renata; Deconinck, Nicolas; Kadhim, Hazim; van Wijk, Richard

    2016-03-01

    We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins. PMID:26883264

  8. Comparing the potential renal protective activity of desferrioxamine B and the novel chelator desferrioxamine B-N-(3-hydroxyadamant-1-yl)carboxamide in a cell model of myoglobinuria.

    PubMed

    Groebler, Ludwig K; Liu, Joe; Shanu, Anu; Codd, Rachel; Witting, Paul K

    2011-05-01

    Accumulating Mb (myoglobin) in the kidney following severe burns promotes oxidative damage and inflammation, which leads to acute renal failure. The potential for haem-iron to induce oxidative damage has prompted testing of iron chelators [e.g. DFOB (desferrioxamine B)] as renal protective agents. We compared the ability of DFOB and a DFOB-derivative {DFOB-AdAOH [DFOB-N-(3-hydroxyadamant-1-yl)carboxamide]} to protect renal epithelial cells from Mb insult. Loading kidney-tubule epithelial cells with dihydrorhodamine-123 before exposure to 100 μM Mb increased rhodamine-123 fluorescence relative to controls (absence of Mb), indicating increased oxidative stress. Extracellular Mb elicited a reorganization of the transferrin receptor as assessed by monitoring labelled transferrin uptake with flow cytometry and inverted fluorescence microscopy. Mb stimulated HO-1 (haem oxygenase-1), TNFα (tumour necrosis factor α), and both ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) gene expression and inhibited epithelial monolayer permeability. Pre-treatment with DFOB or DFOB-AdAOH decreased Mb-mediated rhodamine-123 fluorescence, HO-1, ICAM and TNFα gene expression and restored monolayer permeability. MCP-1 (monocyte chemotactic protein 1) secretion increased in cells exposed to Mb-insult and this was abrogated by DFOB or DFOB-AdAOH. Cells treated with DFOB or DFOB-AdAOH alone showed no change in permeability, MCP-1 secretion or HO-1, TNFα, ICAM or VCAM gene expression. Similarly to DFOB, incubation of DFOB-AdAOH with Mb plus H2O2 yielded nitroxide radicals as detected by EPR spectroscopy, indicating a potential antioxidant activity in addition to metal chelation; Fe(III)-loaded DFOB-AdAOH showed no nitroxide radical formation. Overall, the chelators inhibited Mb-induced oxidative stress and inflammation and improved epithelial cell function. DFOB-AdAOH showed similar activity to DFOB, indicating that this novel low-toxicity chelator may protect the kidney after severe burns. PMID:21320071

  9. Prediction of acute renal failure following soft-tissue injury using the venous bicarbonate concentration.

    PubMed

    Muckart, D J; Moodley, M; Naidu, A G; Reddy, A D; Meineke, K R

    1992-12-01

    Sixty-four patients with soft-tissue injuries were studied prospectively to determine whether an initial venous bicarbonate concentration (VBC) of less than 17 mmol/L would predict the development of myoglobin-induced acute renal failure. The VBC was > 17 mmol/L in 59 patients, seven of whom had myoglobinuria. All recovered without renal complications. The remaining five patients all had VBC < 17 mmol/L and four had myoglobinuria. Acute renal failure developed in four patients (p < 0.001). The VBC on hospital arrival was the most accurate predictor of these patients' risk for the development of acute renal failure following soft-tissue injury. PMID:1474620

  10. Molecular analysis of LPIN1 in Jordanian patients with rhabdomyolysis

    PubMed Central

    Jaradat, Saied A.; Amayreh, Wajdi; Al-Qa'qa', Kefah; Krayyem, Jan

    2015-01-01

    Recessive mutations in LPIN1, which encodes a phosphatidate phosphatase enzyme, are a frequent cause of severe rhabdomyolysis in childhood. Hence, we sequenced the 19 coding exons of the gene in eight patients with recurrent hereditary myoglobinuria from four unrelated families in Jordan. The long-term goal is to facilitate molecular genetic diagnosis without the need for invasive procedures such as muscle biopsies. Three different mutations were detected, including the novel missense mutation c.2395G>C (Gly799Arg), which was found in two families. The two other mutations, c.2174G>A (Arg725His) and c.1162C>T (Arg388X), have been previously identified, and were found to cosegregate with the disease phenotype in the other two families. Intriguingly, patients homozygous for Arg725His were also homozygous for the c.1828C>T (Pro610Ser) polymorphism, and were exercise-intolerant between myoglobinuria episodes. Notably, patients homozygous for Arg388X were also homozygous for the c.2250G>C silent variant (Gly750Gly). Taken together, the data provide family-based evidence linking hereditary myoglobinuria to pathogenic variations in the C-terminal lipin domain of the enzyme. This finding highlights the functional significance of this domain in the absence of structural information. This is the first analysis of LPIN1 in myoglobinuria patients of Jordanian origin, and the fourth such analysis worldwide. PMID:26909335

  11. Severe reversible myopathy due to typhoid.

    PubMed

    Mody, G M; Gathiram, V; Abdulla, E A

    1989-04-01

    An 18-year-old Black male presented to hospital with a fever and inability to walk due to severe proximal myopathy. He was found to have typhoid, and marked elevation of the creatine phosphokinase with myoglobinuria was recorded. After appropriate antibiotic therapy the creatine phosphokinase level returned to normal and the patient made a complete recovery. Although neuropsychiatric manifestations have been commonly recorded in typhoid, the complication of a myopathy has not been frequently noted. PMID:2709478

  12. Myophosphorylase deficiency (McArdle disease) in a patient with normal pregnancy and normal pregnancy outcome

    PubMed Central

    Giles, Warwick; Maher, Catherine

    2011-01-01

    McArdle disease is a rare, mostly autosomal recessive disorder of deficient myophosphorylation of glycogen in skeletal muscles. Recent knowledge regarding this condition means that women of childbearing age with McArdle disease can expect to labour normally without ill effect. We report a case of a 30-year-old woman in her first pregnancy who had an episode of exercise-induced myoglobinuria with a significant rise in serum creatine kinase (CK) levels in early pregnancy who then laboured normally but did require a caesarean section for a malposition of the fetal head.

  13. [Rhabdomyolysis in a well-trained woman after unusually intense exercise].

    PubMed

    Larsen, Christian; Jensen, Mogens Pfeiffer

    2014-06-16

    A 35-year-old woman was acutely hospitalized with oedema of the upper limbs, reduced force, severe movement reduction and muscle pain in both upper extremities. Her symptoms started after three days of intense exercise doing kayaking and a lot of pull-ups in crossfit. Rhabdomyolysis is a syndrome, characterized by muscle necrosis. Usually there is a marked elevation of creatine kinase (CK) concentration with symptoms as described and myoglobinuria (dark coloured urine). After hard muscular work there will often be asymptomatic, but significant elevations in CK concentration, and in rare cases life-threatening rhabdomyolysis with electrolyte imbalances and acute kidney failure. PMID:25352283

  14. Rhabdomyolysis induced by excessive coffee drinking.

    PubMed

    Chiang, W-F; Liao, M-T; Cheng, C-J; Lin, S-H

    2014-08-01

    Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine-containing products. PMID:24220878

  15. Myopathy and parkinsonism in phosphoglycerate kinase deficiency.

    PubMed

    Sotiriou, Evangelia; Greene, Paul; Krishna, Sindu; Hirano, Michio; DiMauro, Salvatore

    2010-05-01

    A 25-year-old man with exertional myoglobinuria had no evidence of hemolytic anemia, but he had severe parkinsonism that was responsive to levodopa. Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy. This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease. PMID:20151463

  16. PGK deficiency.

    PubMed

    Beutler, Ernest

    2007-01-01

    Phosphoglycerate kinase (PGK) deficiency is one of the relatively uncommon causes of hereditary non-spherocytic haemolytic anaemia (HNSHA). The gene encoding the erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations. Twenty-six families have been described and in 20 of these the mutations are known. The reason for different clinical manifestations of mutations of the same gene remains unknown. PMID:17222195

  17. Current concepts in dystrophinopathies.

    PubMed

    Viswanathan, Venkataraman

    2015-02-01

    Dystrophinopathies comprise a group of hereditary muscle disorders characterized by progressive wasting and weakness of skeletal muscle, as a result of degeneration of muscle fibers, and can be distinguished by the mode of transmission, age at onset and pattern of muscle weakness. The range of phenotypes associated with the region Xp21 has been expanding since identification of the gene in 1987. The mild end of the spectrum includes the phenotype of the muscle cramps with myoglobinuria and isolated quadriceps myopathy, while at the severe end, there are progressive muscle diseases that are classified as Duchenne / Becker muscular dystrophy (DMD/BMD). PMID:25416089

  18. Exertional rhabdomyolysis and exercise intolerance revealing dystrophinopathies.

    PubMed

    Figarella-Branger, D; Baeta Machado, A M; Putzu, G A; Malzac, P; Voelckel, M A; Pellissier, J F

    1997-07-01

    Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise intolerance, negative biochemical tests (lipid, glycogen and mitochondrial metabolism) and abnormal immunohistochemistry with at least one anti-dystrophin antibody (anti-Dys 1, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnormal immunoreactivity with all three anti-dystrophin antibodies in two. Immunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal part of the rod domain in one and the distal part of this domain in the other. The clinical, biological and histopathological features of the five patients reported here, together with the previous cases reported in the literature, are described and reveal that exercise intolerance associated with dystrophinopathy displays characteristic clinical, biological and immunohistochemical features and defines a new dystrophinopathy phenotype. The absence of staining in the rod domain provides a secure diagnosis of this syndrome. Dystrophinopathy is one etiology of idiopathic myoglobinuria, requiring genetic counseling. PMID:9224530

  19. A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

    PubMed Central

    2013-01-01

    Background Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria. Methods To identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed. Results WES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn’t exhibit any other symptoms of the previously reported HADHB patients. Conclusions These data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB. PMID:24314034

  20. Gluteal compartment syndrome after prolonged immobilisation.

    PubMed

    Liu, H L; Wong, David S Y

    2009-04-01

    Muscles in the gluteal region are confined by distinct fascial attachments which can potentially result in compartment syndrome. A 74-year-old chronic drinker was admitted to the medical ward after being found drunk on the street. He noticed acute painful swelling of the right side of his buttock the following morning and recalled a slip and fall prior to his blackout. The whole right half of the buttock was tense with erythematous overlying skin. Examination revealed sciatic nerve palsy and myoglobinuria. Emergency fasciotomy and debridement were performed. Intra-operative pressure measurement confirmed a grossly elevated intra-compartmental pressure. Gluteal compartment syndrome is an extremely rare condition and has only been scantily documented previously in case reports. Early diagnosis is crucial but delay recognition is common from lack of knowledge of the condition and readily results in permanent sciatic nerve injury and acute renal shutdown from myoglobinuria. Awareness of the condition, early diagnosis and prompt exploration provide the only chance of avoiding these devastating consequences. Acute swelling diffusely affecting the whole or one side of the buttock, a history of trauma and prolonged local pressure impingement associated with pain out of proportion to the clinical signs should raise a suspicion of this rare condition. PMID:19423461

  1. Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II Deficiency

    PubMed Central

    Vavlukis, M.; Eftimov, A.; Zafirovska, P.; Caparovska, E.; Pocesta, B.; Kedev, S.; Dimovski, A. J.

    2014-01-01

    Aim. To raise the awareness of adult-onset carnitite palmitoyltransferase II deficiency (CPT II) by describing clinical, biochemical, and genetic features of the disease occurring in early adulthood. Method. Review of the case characteristics and literature review. Results. We report on a 20-year-old man presenting with dyspnea, fatigue, fever, and myoglobinuria. This was the second episode with such symptoms (the previous one being three years earlier). The symptoms occurred after intense physical work, followed by a viral infection resulting in fever treated with NSAIDs. Massive rhabdomyolysis was diagnosed, resulting in acute renal failure necessitating plasmapheresis and hemodialysis, acute hepatic lesion, and respiratory insufficiency. Additionally, our patient had cardiomyopathy with volume overload. After a detailed workup, CPT II deficiency was suspected. We did a sequencing analysis for exons 1, 3, and 4 of the CPT II gene and found that the patient was homozygote for Ser 113 Leu mutation in exon 3 of the CPT II gene. The patient recovery was complete except for the cardiomiopathy with mildly impaired systolic function. Conclusion. Whenever a patient suffers recurrent episodes of myalgia, followed by myoglobinuria due to rhabdomyolysis, we should always consider the possibility of this rare condition. The definitive diagnose of this condition is achieved by genetic testing. PMID:24563797

  2. Acute painful paraplegia in a 49-year-old man with allergic asthma.

    PubMed

    Sorino, Claudio; Agati, Sergio; Milani, Giuseppe; Maspero, Annarosa

    2014-01-01

    We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease. PMID:24980994

  3. Rhabdomyolysis in adolescent athletes: review of cases.

    PubMed

    Hummel, Kevin; Gregory, Andrew; Desai, Neerav; Diamond, Alex

    2016-05-01

    Rhabdomyolysis is a syndrome characterized by muscle pain, weakness and myoglobinuria and ranges in severity from asymptomatic to life threatening with acute kidney failure. While a common condition in adult populations, it is understudied in pediatrics and the majority of adolescent cases are likely exercise-induced, caused by strenuous exercise in athletes. Recently, in our pediatric sports medicine practice, we have seen numerous cases of late adolescent high school athletes who present with severe muscle pain and were found to have elevated creatine kinase levels. The cases review potential contributing factors including characteristics of the workout, use of supplements, caffeine, medication, and metabolic or genetic predisposition. Treatment for exercised-induced rhabdomyolysis rarely requires more than rehydration. Return to play should be progressive, individualized, and include acclimatization and monitoring of hydration status, though guidelines require further review. PMID:27031535

  4. A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.

    PubMed

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valérie; Pelosi, Michele; Habarou, Florence; Nguyen Morel, Marie-Ange; Boisson, Bertrand; Vergnaud, Sabrina; Viou, Mai Thao; Nonnenmacher, Luc; Piraud, Monique; Nusbaum, Patrick; Vamecq, Joseph; Romero, Norma; Ottolenghi, Chris; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-11-01

    Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. PMID:25392908

  5. A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

    PubMed Central

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valérie; Pelosi, Michele; Habarou, Florence; Nguyen Morel, Marie-Ange; Boisson, Bertrand; Vergnaud, Sabrina; Viou, Mai Thao; Nonnenmacher, Luc; Piraud, Monique; Nusbaum, Patrick; Vamecq, Joseph; Romero, Norma; Ottolenghi, Chris; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-01-01

    Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. PMID:25392908

  6. Severe Rhabdomyolysis Caused by Plasmodium vivax Malaria in the Brazilian Amazon

    PubMed Central

    Siqueira, André M.; Alexandre, Márcia A. A.; Mourão, Maria P. G.; Santos, Valquir S.; Nagahashi-Marie, Suely K.; Alecrim, Maria G. C.; Lacerda, Marcus V. G.

    2010-01-01

    Severe rhabdomyolysis (creatine phosphokinase = 29,400U/L) developed in a 16-year-old boy from Manaus, Brazil, after he started treatment with chloroquine for infection with Plasmodium vivax. Treatment led to myoglobinuria and acute renal failure. After hemodialysis, the patient improved and a muscle biopsy specimen showed no myophosphorylase or deaminase deficiency. This case of rhabdomyolysis associated with P. vivax infection showed no comorbidities. The pathogenesis is still unclear. Although rhabdomyolysis is generally reported as a complication of Plasmodium falciparum malaria, leading to metabolic and renal complications,1 it has been reported in a patient with P. vivax infection with myoadenylate deaminase deficiency.2 We report a case in a patient without typical muscle enzyme deficiencies in which severe rhabdomyolysis developed while the patients was being treated with chloroquine for a confirmed P. vivax infection. PMID:20682866

  7. A Diagnostic Algorithm for Metabolic Myopathies

    PubMed Central

    Berardo, Andres; DiMauro, Salvatore

    2010-01-01

    Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). PMID:20425236

  8. Update on toxic myopathies.

    PubMed

    Mastaglia, F L; Needham, M

    2012-02-01

    The toxic myopathies are a clinically and pathologically diverse group of disorders that can be caused by a variety of therapeutic agents used in clinical practice, as well as various venoms and other biological toxins. The most important iatrogenic causes are the statin and fibrate cholesterol-lowering agents that can cause a severe necrotizing myopathy and acute rhabdomyolysis and myoglobinuria. The current update focuses on the mechanisms of statin myotoxicity and the importance of genetic predisposing factors for statin myopathy, as well as the recently described form of necrotizing autoimmune myopathy, which is associated with antibodies to the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme and is responsive to aggressive immunotherapy. Mitochondrial myopathies associated with antiretroviral agents and the pyrimidine nucleoside analogue clevudine, and recent reports of myopathies caused by ingestion of red yeast rice and toxic species of mushrooms are also discussed. PMID:21968786

  9. Acute kidney injury: A rare cause.

    PubMed

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  10. Inborn Errors of Energy Metabolism Associated with Myopathies

    PubMed Central

    Das, Anibh M.; Steuerwald, Ulrike; Illsinger, Sabine

    2010-01-01

    Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed. PMID:20589068

  11. Management of acute burns and burn shock resuscitation.

    PubMed

    Faldmo, L; Kravitz, M

    1993-05-01

    Initial management of minor and moderate, uncomplicated burn injury focuses on wound management and patient comfort. Initial management of patients with major burn injury requires airway support, fluid resuscitation for burn shock, treatment for associated trauma and preexisting medical conditions, management of adynamic ileus, and initial wound treatment. Fluid resuscitation, based on assessment of the extent and depth of burn injury, requires administration of intravenous fluids using resuscitation formula guidelines for the initial 24 hours after injury. Inhalation injury complicates flame burns and increases morbidity and mortality. Electrical injury places patients at risk for cardiac arrest, metabolic acidosis, and myoglobinuria. Circumferential full-thickness burns to extremities compromise circulation and require escharotomy or fasciotomy. Circumferential torso burns compromise air exchange and cardiac return. Loss of skin function places patients at risk for hypothermia, fluid and electrolyte imbalances, and systemic sepsis. The first 24 hours after burn injury require aggressive medical management to assure survival and minimize complications. PMID:8489882

  12. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  13. Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

    PubMed

    2016-03-01

    Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather. PMID:27030929

  14. [Rhabdomyolysis in a medical student induced by body-building exercise (rhabdomyolysis following acute muscular exertion)].

    PubMed

    Arányi, J; Radó, J

    1992-08-01

    A medical student sportsman had been admitted to the hospital because of weakness and painful swelling of the muscle as well as dark urine appearing after carrying out an excessive body-building performance. On the basis of indirect evidences pigmenturia "per exclusionem" was a manifestation of urinary myoglobin excretion. The development of an "acute exertional rhabdomyolysis" was confirmed by the increased serum enzyme levels and myoglobinuria. The outcome of the illness was fortunate, as acute renal failure could be avoided. On the basis of survey of the literature it can be stated, that this presumably frequently occurring, but rarely recognized disease may have importance from clinical, sporting medicine and pathophysiological point of view. PMID:1495807

  15. Unusual presentation of phosphoglycerate mutase deficiency due to two different mutations in PGAM-M gene.

    PubMed

    Tonin, Paola; Bruno, Claudio; Cassandrini, Denise; Savio, Chiara; Tavazzi, Eleonora; Tomelleri, Giuliano; Piccolo, Giovanni

    2009-11-01

    Phosphoglycerate mutase (PGAM) deficiency causes a rare metabolic myopathy characterized by exercise-related myalgia and myoglobinuria. This disorder was described in 13 patients and five different mutations in the PGAM-M gene were identified. We report on a new patient with an unusual clinical presentation. As a youth, he participated in different sports without complaining of muscular symptoms, but at 44 years of age, after a brief, intense effort, he experienced lightheadedness without fainting. Serum CK was elevated and the ischemic exercise test showed a pathological lactate response. Muscle biopsy showed only mild abnormalities, but biochemical study revealed a defect of PGAM and genetic analysis showed two different mutations in the PGAM-M gene. Our case expands the clinical spectrum of PGAM deficiency and suggests that the frequency of this metabolic myopathy may be underestimated. PMID:19783439

  16. Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations.

    PubMed

    Spiegel, Ronen; Gomez, Estela Area; Akman, Hasan O; Krishna, Sindu; Horovitz, Yoseph; DiMauro, Salvatore

    2009-03-01

    We describe an 18-year-old man with muscle cramps and recurrent exertional myoglobinuria, without hemolytic anemia or brain dysfunction. Phosphoglycerate kinase (PGK) deficiency was documented in muscle and erythrocytes and molecular analysis of the PGK1 gene identified a novel mutation, T378P. This is the ninth case presenting with isolated myopathy, whereas most other patients show hereditary non-spherocytic hemolytic anemia alone or associated with brain dysfunction, and a few patients have myopathy plus brain involvement. Although the diverse tissue involvement in PGK deficiency remains unclear, all mutations in myopathic patients tend to cluster in the C terminal domain, adjacent to the substrate-binding pocket. This may lead to a failure in the closure of the N terminal and C terminal domains and loss of stability due to lack of inter-domain communication during the catalytic process. PMID:19157875

  17. [Metabolic intolerance to exercise].

    PubMed

    Arenas, J; Martín, M A

    2003-01-01

    Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC. PMID:12838448

  18. Don't be Half-Educated About Haff Disease in Louisiana.

    PubMed

    Diaz, James

    2015-01-01

    Cases of Haff disease, a syndrome of severe myalgia and rhabdomyolysis, have been reported after eating cooked fish in Europe and the US. A retrospective review of US cases was conducted to identify seafood vectors, describe presenting manifestations, and compare the Haff disease toxidrome with other seafood-borne toxidromes. Internet search engines were queried to identify all US reports of Haff disease. The case definition of Haff disease required cooked seafood ingestion history within 24 hours and markedly elevated serum creatine kinase (CK) with CK-muscle/brain (MB) fraction < 5 percent. Twenty-six cases of Haff disease were reported in the US over 30 years, 1984-2014, with spring-summer occurrences. The mean age of cases was 54.8 years without gender difference. Most cases (58 percent) followed consumption of cooked buffalo fish, Ictiobus cyprinellus, (n = 15); other cases followed consumption of boiled crayfish in Louisiana (n = 9) and baked salmon in North Carolina (n = 2). California and Louisiana accounted for most cases (n = 18, p = 0.012). Following mean incubation periods of eight hours; the most common presenting manifestations included vomiting, myalgia, muscle rigidity, chest pain mimicking myocardial infarction, diaphoresis, dyspnea, and brown urine indicating myoglobinuria. Most patients recovered within 2-5 days. Haff disease may follow the consumption of freshwater buffalo fish, freshwater crayfish, and saltwater Atlantic salmon. The bioconcentration of a new, unidentified heat-stable, freshwater and/or brackish/saltwater algal myotoxin in seafood, similar to palytoxin, is suspected of causing Haff disease. Experimental animals fed toxic buffalo fish developed rhabdomyolysis with myoglobinuria. PMID:25978748

  19. Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II

    PubMed Central

    Golbik, Ralph; Sippl, Wolfgang; Zierz, Stephan

    2016-01-01

    Objective: Muscle carnitine palmitoyltransferase (CPT) II deficiency, the most common defect of lipid metabolism in muscle, is characterized by attacks of myoglobinuria without persistent muscle weakness. Methods: His6-N-hCPT2 (wild-type) and His6-N-hCPT2/S113L (variant) were produced recombinantly in prokaryotic host and characterized according to their functional and regulatory properties. Results: The wild-type and the variant S113L showed the same enzymatic activity and thermostability at 30°C. The mutated enzyme, however, revealed an abnormal thermal destabilization at 40°C and 45°C. This was consistent with an increased flexibility (B-factor) of the variant at 40°C compared with that of the wild-type shown by molecular dynamics analysis. Preincubation of the enzymes with l-carnitine and acyl-l-carnitines containing more than 10 carbons in the acyl side-chain stabilized the mutated enzyme against thermal inactivation. In contrast, palmitoyl-CoA destabilized both enzymes. Conclusions: The problems in CPT II deficiency originating from the S113L mutation are not caused by the loss of catalytically active enzyme. They might be at least partially related to an impaired thermal stability of the protein. The lower thermodynamic stability of the variant might explain why fever and prolonged exertion provoke attacks of myoglobinuria in CPT II deficiency. The stabilization by acyl-l-carnitines might provide the basis for possible preventive therapy of CPT II deficiency. PMID:27123472

  20. Influence of the Environment on Body Temperature of Racing Greyhounds

    PubMed Central

    McNicholl, Jane; Howarth, Gordon S.; Hazel, Susan J.

    2016-01-01

    Heat strain is a potential risk factor for racing greyhounds in hot climates. However, there have been limited studies into the incidence of heat strain (when excess heat causes physiological or pathological effects) in racing greyhounds. The aim of this study was to determine if heat strain occurs in racing greyhounds, and, if so, whether environmental factors (e.g., ambient temperature and relative humidity) or dog-related factors (e.g., sex, bodyweight, color) are associated with the risk of heat strain. A total of 229 greyhounds were included in over 46 race meetings and seven different race venues in South Australia, Australia. Rectal temperatures of dogs were measured pre- and postrace and urine samples collected for analysis of myoglobinuria. Ambient temperature at race times ranged between 11.0 and 40.8°C and relative humidity ranged from 17 to 92%. There was a mean increase in greyhound rectal temperature of 2.1°C (range 1.1–3.1°C). A small but significant association was present between ambient temperature and increase in rectal temperature (r2 = 0.033, P = 0.007). The mean ambient temperature at race time, of dogs with postrace rectal temperature of or exceeding 41.5°C, was significantly greater than at race time of dogs with a postrace rectal temperature ≤41.5°C (31.2 vs. 27.3°C, respectively, P = 0.004). When the ambient temperature reached 38oC, over one-third (39%) of dogs had a rectal temperature >41.5°C. Over half of postrace urine samples were positive by Dipstick reading for hemoglobin/myoglobin, and of 77 urine samples positive for Dipstick readings, 95% were positive for myoglobin. However, urinary myoglobin levels were not associated with ambient temperature or postrace rectal temperatures. The mean increase in rectal temperature was greater in dark (black, blue, brindle) than light (fawn and white) colored greyhounds. The results suggest heat strain occurs in racing greyhounds, evidenced by postrace rectal temperatures

  1. Influence of the Environment on Body Temperature of Racing Greyhounds.

    PubMed

    McNicholl, Jane; Howarth, Gordon S; Hazel, Susan J

    2016-01-01

    Heat strain is a potential risk factor for racing greyhounds in hot climates. However, there have been limited studies into the incidence of heat strain (when excess heat causes physiological or pathological effects) in racing greyhounds. The aim of this study was to determine if heat strain occurs in racing greyhounds, and, if so, whether environmental factors (e.g., ambient temperature and relative humidity) or dog-related factors (e.g., sex, bodyweight, color) are associated with the risk of heat strain. A total of 229 greyhounds were included in over 46 race meetings and seven different race venues in South Australia, Australia. Rectal temperatures of dogs were measured pre- and postrace and urine samples collected for analysis of myoglobinuria. Ambient temperature at race times ranged between 11.0 and 40.8°C and relative humidity ranged from 17 to 92%. There was a mean increase in greyhound rectal temperature of 2.1°C (range 1.1-3.1°C). A small but significant association was present between ambient temperature and increase in rectal temperature (r (2) = 0.033, P = 0.007). The mean ambient temperature at race time, of dogs with postrace rectal temperature of or exceeding 41.5°C, was significantly greater than at race time of dogs with a postrace rectal temperature ≤41.5°C (31.2 vs. 27.3°C, respectively, P = 0.004). When the ambient temperature reached 38(o)C, over one-third (39%) of dogs had a rectal temperature >41.5°C. Over half of postrace urine samples were positive by Dipstick reading for hemoglobin/myoglobin, and of 77 urine samples positive for Dipstick readings, 95% were positive for myoglobin. However, urinary myoglobin levels were not associated with ambient temperature or postrace rectal temperatures. The mean increase in rectal temperature was greater in dark (black, blue, brindle) than light (fawn and white) colored greyhounds. The results suggest heat strain occurs in racing greyhounds, evidenced by postrace rectal

  2. [Rhabdomyolysis].

    PubMed

    Rosa, Nuno Guimarães; Silva, Gil; Teixeira, Alves; Rodrigues, Fernando; Araújo, José Augusto

    2005-01-01

    Rhabdomyolysis is a common entity that often has a multifactorial etiology. It usually affects healthy individuals, following trauma, excessive physical activity, convulsive crisis, alcohol and other drugs consumption or infections. Accumulation of intracellular calcium, activation of proteases and lipases, production of free radicals and the infiltration by inflammatory cells, are some of the mechanisms responsible for muscular necrosis. Myoglobinuric acute renal failure (ARF) is only possible in the presence of myoglobin, liberated by the muscle cells, and of hypovolemia/renal hypoperfusion. One of the most important complications of this entity is electrolyte disturbance (hyperkalemia, hypocalcemia, metabolic acidosis), that can be aggravated by the establishment of ARF. The diagnosis of rhabdomyolysis relies on the elevation of creatine kinase and on the presence of myoglobinuria. The main therapeutic goals are removal of precipitating factors, handling of biochemical complications, prevention and treatment of ARF using renal replacement techniques when necessary. Early diagnosis and treatment are of critical importance in epidemic forms of rhabdomyolysis (e. g. earthquakes) often associated with ARF. In this setting, the quick access to the dialysis equipment and human resources can be compromised and conservative measures, as an early and vigorous hydratation associated with a forced alkaline diuresis, can improve the prognosis of this complication. PMID:16584660

  3. Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency: clinical and biochemical differences with the fatal cardiac phenotype.

    PubMed

    Scholte, H R; Van Coster, R N; de Jonge, P C; Poorthuis, B J; Jeneson, J A; Andresen, B S; Gregersen, N; de Klerk, J B; Busch, H F

    1999-07-01

    A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. Fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. Fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio. PMID:10407852

  4. Enhydrina schistosa (Elapidae: Hydrophiinae) the most dangerous sea snake in Sri Lanka: three case studies of severe envenoming.

    PubMed

    Kularatne, S A M; Hettiarachchi, R; Dalpathadu, J; Mendis, A S V; Appuhamy, P D S A N; Zoysa, H D J; Maduwage, K; Weerasinghe, V S; de Silva, A

    2014-01-01

    Sea snakes are highly venomous and inhabit tropical waters of the Indian and Pacific Oceans. Enhydrina schistosa is a common species of sea snake that lives in the coastal waters, lagoons, river mouths and estuaries from the Persian Gulf through Sri Lanka and to Southeast Asia. It is considered one of the most aggressive sea snakes in Sri Lanka where fishermen and people wading are at high risk. However, sea snake bites are rarely reported. In this report, we describe three cases where E. schistosa was the offending species. These three patients presented to two hospitals on the west coast of Sri Lanka within the course of 14 months from November 2011 with different degrees of severity of envenoming. The first patient was a 26-year-old fisherman who developed severe myalgia with very high creatine kinase (CK) levels lasting longer than 7 days. The second patient was a 32-year-old fisherman who developed gross myoglobinuria, high CK levels and hyperkalaemia. Both patients recovered and their electromyographic recordings showed myopathic features. The nerve conduction and neuromuscular transmission studies were normal in both patients suggesting primary myotoxic envenoming. The third patient was a 41-year-old man who trod on a sea snake in a river mouth and developed severe myalgia seven hours later. He had severe rhabdomyolysis and died three days later due to cardiovascular collapse. In conclusion, we confirm that E. schistosa is a deadly sea snake and its bite causes severe rhabdomyolysis. PMID:24239658

  5. [Overactive muscles: it can be more serious than common myalgia or cramp].

    PubMed

    Molenaar, J P F; Snoeck, M M J; Voermans, N C; van Engelen, B G M

    2016-01-01

    Positive muscle phenomena are due to muscle overactivity. Examples are cramp, myalgia, and stiffness. These manifestations have mostly acquired causes, e.g. side-effects of medication, metabolic disorders, vitamin deficiency, excessive caffeine intake or neurogenic disorders. We report on three patients with various positive muscle phenomena, to illustrate the clinical signs that indicate an underlying myopathy. Patient A, a 56-year-old man, was diagnosed with muscle cramp in the context of excessive coffee use and previous lumbosacral radiculopathy. Patient B, a 71-year-old man, was shown to have RYR1-related myopathy. Patient C, a 42-year-old man, suffered from Brody myopathy. We propose for clinicians to look out for a number of 'red flags' that can point to an underlying myopathy, and call for referral to neurology if indicated. Red flags include second wind phenomenon, familial occurrence of similar complaints, marked muscle stiffness, myotonia, muscle weakness, muscle hypertrophy, and myoglobinuria. Establishing a correct diagnosis is important for proper treatment. Certain myopathies call for cardiac or respiratory screening. PMID:27122070

  6. Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene.

    PubMed

    Taglia, Antonella; Petillo, Roberta; D'Ambrosio, Paola; Picillo, Esther; Torella, Annalaura; Orsini, Chiara; Ergoli, Manuela; Scutifero, Marianna; Passamano, Luigia; Palladino, Alberto; Nigro, Gerardo; Politano, Luisa

    2015-05-01

    Becker muscular dystrophy (BMD) was first described in 1953 by Emile Becker as a benign variant of Duchenne muscular Dystrophy (DMD). Compared with DMD, BMD is clinically more heterogeneous, with initial presentation in the teenage years and loss of ambulation beyond the age of 16 and a wide spectrum of clinical presentations, ranging from only myalgias and muscle cramps to exercise intolerance and myoglobinuria, asymptomatic elevation of serum creatin-kinase, or mild limb-girdle weakness and quadriceps myopathy. About 50% of patients become symptomatic by the age of 10 and the most part by the age of 20 years. However few patients can be free of symptoms till their fifties and cases of late-onset Becker Muscular Dystrophy have also been described. In this report we describe the clinical features of patients with dystrophinopathy sharing a deletion of exons 45-55, occasionally or retrospectively diagnosed. These data are important for both the prognostic aspects of children presenting this dystrophin gene mutation, and for the genetic counseling in these families (reassuring them on the benign course of the disease), and last but not least to keep in mind a diagnosis of BMD in asymptomatic adults with mild hyperckemia. PMID:26155064

  7. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  8. Methicillin-resistant Staphylococcus aureus infected gluteal compartment syndrome with rhabdomyolysis in a bodybuilder

    PubMed Central

    Woon, Colin YL; Patel, Kushal R; Goldberg, Benjamin A

    2016-01-01

    Gluteal compartment syndrome (GCS) is a rare condition. We present a case of gluteal muscle strain with hematoma formation, methicillin-resistant Staphylococcus aureus (MRSA) superinfection, leading to acute GCS, rhabdomyolysis and acute kidney injury. This combination of diagnoses has not been reported in the literature. A 36-year-old Caucasian male presented with buttock pain, swelling and fever after lifting weights. Gluteal compartment pressure was markedly elevated compared with the contralateral side. Investigations revealed elevated white blood cell, erythrocyte sedimentation rate, C-reactive protein, creatine kinase, creatinine and lactic acid. Urinalysis was consistent with myoglobinuria. Magnetic resonance imaging showed increased T2 signal in the gluteus maximus and a central hematoma. Cultures taken from the emergency debridement and fasciotomy revealed MRSA. He had repeat, debridement 2 d later, and delayed primary closure 3 d after. GCS is rare and must be suspected when patients present with pain and swelling after an inciting event. They are easily diagnosed with compartment pressure monitoring. The treatment of gluteal abscess and compartment syndrome is the same and involves rapid surgical debridement. PMID:27190761

  9. Paraphenylenediamine Containing Hair Dye: An Emerging Household Poisoning.

    PubMed

    Patra, Ambika Prasad; Shaha, Kusa Kumar; Rayamane, Anand P; Dash, Shreemanta Kumar; Mohanty, Manoj Kumar; Mohanty, Sachidananda

    2015-09-01

    Paraphenylenediamine poisoning is among one of the emerging causes of poisoning in Asian countries, because it is a constituent of hair dye formulations and is easily available in market at low cost. Hair dyes are rampantly used in Asian households compared with the western world. Locally, hair dye constituents may have allergic adverse effects, and acute systemic poisoning presents with characteristic angioedema, upper airway obstruction, rhabdomyolysis, methemoglobinemia, myoglobinuria, and acute renal failure. This study reports about the death of a 24-year-old Indian housewife who committed suicide by taking hair dye emulsion. She had an argument with her husband, and because of fit of rage, took a bowlful (80 mL) of hair dye emulsion kept prepared for the use by husband. She developed angioedema, cervical swelling, and rhabdomyolysis and died of acute renal failure within 24 hours. Toxicological analysis of viscera and blood revealed varying levels of paraphenylenediamine. Histopathological samples of kidney showed features of acute tubular necrosis and myoglobin casts in renal tubules. The aim of the study is to create awareness about the adverse effects of the hair dye, its poisoning outcome, and possible preventive measures. PMID:26056768

  10. Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats.

    PubMed

    Shelton, G Diane

    2010-09-01

    The diagnosis of neuromuscular diseases can be challenging. The first step is recognition that the disease involves the neuromuscular system (muscle, neuromuscular junction, peripheral nerve, and ventral horn cells of the spinal cord). Many neuromuscular diseases share clinical signs and cannot be distinguished based on clinical examination. Routine laboratory screening, including a CBC, biochemical profile, and urinalysis, can identify some of the most common systemic abnormalities that cause muscle weakness and myalgia, such as hypo- and hyperglycemia, electrolyte disorders, or thyroid abnormalities, and may suggest a specific diagnosis, such as diabetes mellitus, hypo- or hyperadrenocorticism, renal failure, or hypothyroidism. Increased creatine kinase activity, increased cardiac troponin I concentration, and myoglobinuria are useful in detecting skeletal and cardiac muscle damage. Identification of acetylcholine receptor antibodies is diagnostic for acquired myasthenia gravis. For primary muscle or peripheral nerve diseases, tissue biopsy is the most direct way to determine specific pathology, correctly classify the disease, and determine the course of additional laboratory testing. For example, inflammatory, necrotizing, dystrophic, metabolic, or congenital myopathies require different laboratory testing procedures for further characterization. Many neuromuscular diseases are inherited or breed-associated, and DNA-based tests may already be established or may be feasible to develop after the disorder has been accurately characterized. This review focuses on both routine and specialized laboratory testing necessary to reach a definitive diagnosis and determine an accurate prognosis for neuromuscular diseases. PMID:20726955

  11. [Isotretinoin and exercise: can the two walk together?].

    PubMed

    Dalal, Adam; Ben-Barak, Shira; Zlotogorski, Abraham; Constantini, Naama

    2014-02-01

    Since its introduction in 1982, isotretinoin has revolutionized acne treatment, targeting the underlying mechanism of the disease, with effective and long-lasting results. During the first decade of its marketing, several cases of hyperCKemia and rhabdomyolysis were linked to isotretinon therapy. A special concern was given to the possible triggering of muscle toxicity by vigorous exercise. These potential effects discouraged the prescription of isotretinoin to physically active patients or required them to abstain from exercise during treatment. Common musculoskeletal adverse effects of isotretinoin include muscle or joint pains. HyperCKemia is frequently found in patients receiving treatment for rare cases of rhabdomyolysis. Isotretinoin-associated muscle toxicity is usually detected in asymptomatic patients, even though symptoms can appear without hyperCKemia. A possible synergistic effect of isotretinoin and exercise is plausible, although supported by weak evidence and mediated by an unknown mechanism. There are only two reports of myoglobinuria and no reports of decreased renal function in exercising patient under treatment. In conclusion, we believe that current data should not deter physicians from offering isotretinoin to physically active patients nor require them to abstain from exercise. Physicians must explain to patients the possible side effects of treatment, ask them to refrain from an unusual change in their exercise regimen and advise them to avoid other triggers of rhabdomyolysis. Patients should be aware of possible signs of muscle toxicity and inform their doctors about any relevant symptoms. PMID:24716429

  12. Clinical Scenarios in Acute Kidney Injury: Parenchymal Acute Kidney Injury-Tubulo-Interstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria; Ronco, Claudio

    2016-01-01

    Acute tubular necrosis (ATN) is the most common type of acute kidney injury (AKI) related to parenchymal damage (90% of cases). It may be due to a direct kidney injury, such as sepsis, drugs, toxins, contrast media, hemoglobinuria and myoglobinuria, or it may be the consequence of a prolonged systemic ischemic injury. Conventional ultrasound (US) shows enlarged kidneys with hypoechoic pyramids. Increased volume is largely sustained by the increase of anteroposterior diameter, while longitudinal axis usually maintains its normal length. Despite the role of color Doppler in AKI still being debated, many studies demonstrate that renal resistive indexes (RIs) vary on the basis of primary disease. Moreover, several studies assessed that higher RI values are predictive of persistent AKI. Nevertheless, due to the marked heterogeneity among the studies, further investigations focused on timing of RI measurement and test performances are needed. Acute interstitial nephritis is also a frequent cause of AKI, mainly due to non-steroidal anti-inflammatory drugs and antibiotics administration. The development of acute interstitial nephritis is due to an immunological reaction against nephritogenic exogenous antigens, processed by tubular cells. In acute interstitial nephritis, as well as in ATN, conventional US does not allow a definitive diagnosis. Kidneys appear enlarged and widely hyperechoic due to interstitial edema and inflammatory infiltration. Also, in this condition, hemodynamic changes are closely correlated to the severity and the progression of the anatomical damage. PMID:27169885

  13. [Unusual and fatal type of burn injury: hot air sauna burn].

    PubMed

    García-Tutor, E; Koljonen, V

    2007-01-01

    Sauna bathing is a popular recreational activity in Finland and is generally considered safe even for pregnant women and patients suffering from heart problems; but mixing alcohol with sauna bathing can be hazardous. In the normal Finnish recreational sauna the temperature is usually between 80 and 90 degrees C. A wide variety of burn injuries, in all age groups, are related to sauna bathing; scalds and contact burns account for over 85% while hot air, steam and flame burns for only 15%. Dehydration in patients under the influence of alcohol heightens the risk of hypotension which impairs skin blood circulation. This increased warming of the skin is an effect that is more marked on the outer and upper parts of the body exposed to hot air. Such patients require intensive care on admission: fluid replacement according to the Parkland formula, forced diuresis and immediate correction of acidosis and myoglobinuria. These patients have significant rhabdomyolysis on admission. The best predictor of survival is the creatine kinase level on the second post-injury day. CT scans are necessary to diagnose the underlying conditions of unconsciousness. The necrotic area extends to subcutaneous fat tissue and even to the underlying muscles. The level of excision is typically fascial and, in some areas, layers of the muscle must be removed. Owing to the popularity of sauna bathing throughout the world, it is important to know the extent of damage in this type of injury, in order not to underestimate the severity of such lesions. PMID:17886710

  14. A multi-parametric protocol to study exercise intolerance in McArdle's disease.

    PubMed

    Ricci, Giulia; Bertolucci, Federica; Logerfo, Annalisa; Simoncini, Costanza; Papi, Riccardo; Franzoni, Ferdinando; Dell'Osso, Giacomo; Servadio, Adele; Masoni, Maria Chiara; Siciliano, Gabriele

    2015-12-01

    McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi-parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet. PMID:27199539

  15. PubMed Central

    Logerfo, Annalisa; Simoncini, Costanza; Papi, Riccardo; Franzoni, Ferdinando; Dell'Osso, Giacomo; Servadio, Adele; Masoni, Maria Chiara

    2015-01-01

    McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi-parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet. PMID:27199539

  16. Macrophagic myofasciitis in children is a localized reaction to vaccination.

    PubMed

    Lach, Boleslaw; Cupler, Edward J

    2008-06-01

    Macrophagic myofasciitis is a novel, "inflammatory myopathy" described after a variety of vaccinations, almost exclusively in adults. We examined the relevance of histological findings of this myopathy to the clinical presentation in pediatric patients. Muscle biopsies from 8 children (7 months to 6 years old) with histological features of macrophagic myofasciitis were reviewed and correlated with the clinical manifestations. Patients underwent quadriceps muscle biopsy for suspected mitochondrial disease (4 patients), spinal muscular atrophy (2 patients), myoglobinuria (1 patient), and hypotonia with motor delay (1 patient). All biopsies showed identical granulomas composed of periodic acid-Schiff-positive and CD68-positive macrophages. Characteristic aluminum hydroxide crystals were identified by electron microscopy in 2 cases. The biopsy established diagnoses other than macrophagic myofasciitis in 5 patients: spinal muscular atrophy (2), Duchenne muscular dystrophy (1), phospho-glycerate kinase deficiency (1), and cytochrome c oxidase deficiency (1). Three children with manifestations and/or a family history of mitochondrial disease had otherwise morphologically normal muscle. All children had routine vaccinations between 2 months and 1 year before the biopsy, with up to 11 intramuscular injections, including the biopsy sites. There was no correlation between histological findings of macrophagic myofasciitis in biopsies and the clinical symptoms. We believe that macrophagic myofasciitis represents a localized histological hallmark of previous immunization with the aluminum hydroxide adjuvants contained in vaccines, rather than a primary or distinct inflammatory muscle disease. PMID:18281624

  17. Tarui disease and distal glycogenoses: clinical and genetic update.

    PubMed

    Toscano, A; Musumeci, O

    2007-10-01

    Phosphofructokinase deficiency (Tarui disease) was the first disorder recognized to directly affect glycolysis. Since the discovery of the disease, in 1965, a wide range of biochemical, physiological and molecular studies have greatly contributed to our knowledge concerning not only phosphofructokinase function in normal muscle but also on the general control of glycolysis and glycogen metabolism. Studies on phosphofructokinase deficiency vastly enriched the field of glycogen storage diseases, making a relevant improvement also in the molecular genetic area. So far, more than one hundred patients have been described with prominent clinical symptoms characterized by muscle cramps, exercise intolerance, rhabdomyolysis and myoglobinuria, often associated with haemolytic anaemia and hyperuricaemia. The muscle phosphofructokinase gene is located on chromosome 12 and about 20 mutations have been described. Other glycogenoses have been recognised in the distal part of the glycolytic pathway: these are infrequent but some may induce muscle cramps, exercise intolerance and rhabdomyolysis. Phosphoglycerate Kinase, Phosphoglycerate Mutase, Lactate Dehydrogenase, beta-Enolase and Aldolase A deficiencies have been described as distal glycogenoses. From the molecular point of view, the majority of these enzyme deficiencies are sustained by "private" mutations. PMID:18421897

  18. A diagnostic algorithm for metabolic myopathies.

    PubMed

    Berardo, Andres; DiMauro, Salvatore; Hirano, Michio

    2010-03-01

    Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). Fig. 1 Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK-creatine kinase; COX-cytochrome c oxidase; CPT-carnitine palmitoyl transferase; cyt b-cytochrome b; mtDNA-mitochondrial DNA; nDNA-nuclear DNA; PFK-phosphofructokinase; PGAM-phosphoglycerate mutase; PGK-phosphoglycerate kinase; PPL-myophosphorylase; RRF-ragged red fibers; TFP-trifunctional protein deficiency; VLCAD-very long-chain acyl-coenzyme A dehydrogenase. PMID:20425236

  19. Diagnosis of Snakebite and the Importance of Immunological Tests in Venom Research

    PubMed Central

    Theakston, R. David G.; Laing, Gavin D.

    2014-01-01

    In many cases of envenoming following snake bite, the snake responsible for the accident remains unidentified; this frequently results in difficulty deciding which antivenom to administer to the systemically-envenomed victim, especially when only monospecific antivenoms are available. Normally the specific diagnosis of snake bite can be conveniently made using clinical and laboratory methods. Where clinical diagnosis depends upon the recognition of specific signs of envenoming in the patient, laboratory diagnosis is based on the changes which occur in envenomed victims including the detection of abnormalities in blood parameters, presence/absence of myoglobinuria, changes in certain enzyme levels, presence/absence of neurotoxic signs and the detection in the blood of specific venom antigens using immunologically-based techniques, such as enzyme immunoassay. It is the latter which is the main subject of this review, together with the application of techniques currently used to objectively assess the effectiveness of new and existing antivenoms, to assess first aid measures, to investigate the possible use of such methods in epidemiological studies, and to detect individual venom components. With this in mind, we have discussed in some detail how such techniques were developed and how they have helped in the treatment of envenoming particularly and in venom research in general. PMID:24859244

  20. [A case of acute renal failure following compartment syndrome after the surgery for femoral neck fracture].

    PubMed

    Koda, Kenichiro; Uzawa, Masashi; Ide, Yasuo; Harada, Masaki; Sanbe, Norie; Sugano, Takayuki; Satoh, Yasuo; Tagami, Megumi

    2013-02-01

    Compartment syndrome is known to develop after a prolonged surgery in the lithotomy position. We experienced acute renal failure following compartment syndrome after the surgery in hemilithotomy position. A 62-year-old man underwent a left hip fixation for femoral neck fracture. The surgical leg was placed into traction in a foot piece and the intact leg was placed in the hemilithotomy position. Because of the difficulty in repositioning and the trouble with fluoroscope, the surgery took over 5 hours. He suffered acute pain, swelling and spasm in his intact leg placed into hemilithotomy after the surgery. Creatine kinase, blood urea nitrogen and creatinine markedly increased and myoglobinuria was recognized. We diagnosed an acute renal failure following compartment syndrome and treated him in the ICU on close monitoring. In spite of the treatment with massive transfusion and diuretics, he needed hemodialysis twice and then his renal function improved. Prevention is most essential for compartment syndrome after a prolonged surgery in the lithotomy position. Risk factors should be recognized before surgery and appropriate action should be taken such as using Allen stirrups and avoiding hypotension, hypovolemia and the prolonged lithotomy position with exaggerated elevation of legs. PMID:23479927

  1. Methicillin-resistant Staphylococcus aureus infected gluteal compartment syndrome with rhabdomyolysis in a bodybuilder.

    PubMed

    Woon, Colin Yl; Patel, Kushal R; Goldberg, Benjamin A

    2016-05-18

    Gluteal compartment syndrome (GCS) is a rare condition. We present a case of gluteal muscle strain with hematoma formation, methicillin-resistant Staphylococcus aureus (MRSA) superinfection, leading to acute GCS, rhabdomyolysis and acute kidney injury. This combination of diagnoses has not been reported in the literature. A 36-year-old Caucasian male presented with buttock pain, swelling and fever after lifting weights. Gluteal compartment pressure was markedly elevated compared with the contralateral side. Investigations revealed elevated white blood cell, erythrocyte sedimentation rate, C-reactive protein, creatine kinase, creatinine and lactic acid. Urinalysis was consistent with myoglobinuria. Magnetic resonance imaging showed increased T2 signal in the gluteus maximus and a central hematoma. Cultures taken from the emergency debridement and fasciotomy revealed MRSA. He had repeat, debridement 2 d later, and delayed primary closure 3 d after. GCS is rare and must be suspected when patients present with pain and swelling after an inciting event. They are easily diagnosed with compartment pressure monitoring. The treatment of gluteal abscess and compartment syndrome is the same and involves rapid surgical debridement. PMID:27190761

  2. Lethal carnitine palmitoyltransferase (CPT) II deficiency in newborns: A molecular-genetic study

    SciTech Connect

    Taroni, F.; Gellera, C.; Cavadini, P.

    1994-09-01

    Classically, CPT II deficiency presents in young adults with recurrent episodes of paroxysmal myoglobinuria triggered by prolonged exercise, cold, or fever. More severe forms of CPT II deficiency have recently been observed in children and newborns. Here, were present biochemical and molecular studies of lethal neonatal CPT II deficiency in a premature Haitian infant of nonconsanguineous parents. He presented at birth with severe respiratory distress, cardiac arrhythmia and heart failure. His condition worsened and he died on the 4th day of life. Postmortem examination showed hypertrophied, dilated heart, and lipid storage in liver, heart and kidney. An older sibling had died unexpectantly at 4 days of age with postmortem evidence of fatty infiltration of liver, kidney, heart and muscle. Biochemical study of cultured fibroblasts demonstrated dramatic reduction of palmitate oxidation (to < 3%) and very low residual CPT II activity ({le}15%). No CPT II protein was detected by Western blot analysis of fibroblasts. However, immunoprecitation of cells pulse-labeled with L-[{sup 35}S] methionine demonstrated normal amounts of newly synthesized CPT II, thus suggesting altered stability of the enzyme. To identify the molecular defect in his patient, individual CPT II exons were amplified by genomic PCR and directly sequenced. A missense mutation was found in exon 4, resulting in the nonconservative amino acid substitution at codon 227 (Pro227Leu). SSCP analysis of a genomic PCR fragment encompassing the mutation demonstrated that the patient was homozygous and the parents were heterozygous for this mutation. The mutation was detected neither in a large number of controls nor in other CPT II deficient patients. Finally, CPT II activity in COS-1 cells transfected with mutated CPT II cDNA was <8% than that in cells transfected with wild-type cDNA, thus demonstrating the pathogenic role of this mutation.

  3. Carnitine palmitoyltransferase II (CPT II) deficiency: genotype-phenotype analysis of 50 patients.

    PubMed

    Joshi, Pushpa Raj; Deschauer, Marcus; Zierz, Stephan

    2014-03-15

    Clinical, biochemical and molecular genetic data in a cohort of 50 patients with muscle CPT II deficiency are reported. Attacks of myoglobinuria occurred in 86% of patients. In 94% of patients the triggering factor was exercise. Although the myopathic form is often called the adult from, in 60% of patients, the age of onset was in childhood (1-12 years). All the patients in whom biochemical activity was measured had normal enzyme activity of total CPT I+II but the activity was significantly inhibited by malonyl-CoA and Triton. The p.S113L mutation was detected in 38/40 index patients (95%) in at least one allele. Sixty percent of index patients were homozygous for this mutation. Thirteen other mutations, all in compound heterozygote form, were also identified. There was no significant difference in ages of onset, clinical and biochemical phenotype of patients with p.S113L mutation in homozygous or compound heterozygous form. The exception was a tendency of slightly higher residual enzyme activity upon malonyl-CoA inhibition in compound heterozygotes. Phenotype was also not significantly different in patients with missense mutations on both alleles and patients with truncating mutation on one allele and missense mutation on the other allele. However, the only exception was that, attacks were triggered by fasting in almost all the patients with truncating mutations. In contrast, fasting triggered the attacks only in one third of patients with missense mutations on both alleles. The data indicate that within the muscle form of CPT II deficiency, the various genotypes have only marginal influence on the clinical and biochemical phenotype. PMID:24398345

  4. Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency.

    PubMed

    Haviv, Ruby; Zeharia, Avraham; Belaiche, Corinne; Haimi Cohen, Yishai; Saada, Ann

    2014-02-01

    The E3 subunit of the pyruvate dehydrogenase complex (dihydrolipoamide dehydrogenase/dihydrolipoyl dehydrogenase/DLD/lipoamide dehydrogenase/LAD), is a mitochondrial matrix enzyme and also a part of the branched-chain ketoacid dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. DLD deficiency (MIM #246900), is relatively frequent in the Ashkenazi Jewish population but occurs in other populations as well. Early diagnosis is important to prevent episodes of metabolic decompensation, liver failure, and encephalopathy. The clinical presentations are varied and may include Reye-like syndrome, hepatic failure, myopathy, and myoglobinuria. Laboratory markers, such as elevated urinary alpha-ketoglutarate, blood pyruvate, lactate, and ammonia, are mostly nonspecific and not always present, making the diagnosis difficult. Since we observed elevated plasma citrulline levels in a number of confirmed cases, we retrospectively examined the value of citrulline as a biochemical marker for DLD deficiency. Data was gathered from the files of 17 pediatric patients with DLD deficiency, confirmed by enzymatic and genetic analysis. The control group included 19 patients in whom urea cycle defects were ruled out but DLD deficiency was suspected. Seven of the DLD-deficient patients presented with elevated plasma citrulline levels (median value 205 μM, range 59-282 μM) (normal range 1-45 μM) while none in the control patient group. In five patients, elevated citrulline was associated with elevated plasma glutamine and metabolic acidosis. Interestingly, elevated plasma citrulline was associated with the common G229C mutation. In conclusion, we suggest that elevated plasma citrulline in the absence of urea cycle defects warrants an investigation for DLD deficiency. PMID:23995961

  5. The Spectrum of Renal Involvement in Patients With Inflammatory Myopathies

    PubMed Central

    Couvrat-Desvergnes, Grégoire; Masseau, Agathe; Benveniste, Olivier; Bruel, Alexandra; Hervier, Baptiste; Mussini, Jean-Marie; Buob, David; Hachulla, Eric; Rémy, Philippe; Azar, Raymond; Namara, Evelyne Mac; MacGregor, Brigitte; Daniel, Laurent; Lacraz, Adeline; Broucker, Thomas De; Rouvier, Philippe; Carli, Philippe; Laville, Maurice; Dantan, Etienne; Hamidou, Mohamed; Moreau, Anne

    2014-01-01

    Abstract Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM. PMID:24378741

  6. A phase I/pilot study of radiofrequency ablation for the treatment of recurrent pediatric solid tumors

    PubMed Central

    Hoffer, Fredric A.; Daw, Najat C.; Xiong, Xiaoping; Anghelescu, Doralina; Krasin, Matthew; Yan, Xiaowei; Davidoff, Andrew M.; Furman, Wayne L.; Rodriguez-Galindo, Carlos; Spunt, Sheri L.

    2010-01-01

    Background This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors. Methods From 2003 through 2008, we conducted a phase I/pilot study of RFA for recurrent pediatric solid tumors. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 and 3 months prospectively. Accrual stopped in 2006 and data collection stopped in 2008. Results Sixteen patients (age 4 – 33 years, median 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Post-procedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range 2–25 days, median 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within one month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients all without renal damage. Serious complications from pulmonary RFA included two diaphragmatic hernias. Twenty-four of 82 (29%) lesions imaged remained ablated at the end of the study. Conclusion The toxicity from RFA of recurrent pediatric solid tumors is real but limited and RFA may offer a local tumor control alternative in carefully selected cases. PMID:19180637

  7. Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

    PubMed

    Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

    2015-01-01

    Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients. PMID:25181966

  8. The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

    PubMed

    Faiz, Abul; Ghose, Aniruddha; Ahsan, Farid; Rahman, Ridwanur; Amin, Robed; Hassan, Mahtab Uddin; Chowdhury, A Wahed; Kuch, Ulrich; Rocha, Thalita; Harris, John B; Theakston, R David G; Warrell, David A

    2010-11-01

    Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (β-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and

  9. What Caused the UK's Largest Common Dolphin (Delphinus delphis) Mass Stranding Event?

    PubMed Central

    Jepson, Paul D.; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell Jr., Robert L.; Clare, Frances C.; Davison, Nick; Law, Robin J.; Loveridge, Jan; Macgregor, Shaheed K.; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W.; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L.; Tregenza, Nick; Cunningham, Andrew A.; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3–4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID

  10. What caused the UK's largest common dolphin (Delphinus delphis) mass stranding event?

    PubMed

    Jepson, Paul D; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell, Robert L; Clare, Frances C; Davison, Nick; Law, Robin J; Loveridge, Jan; Macgregor, Shaheed K; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L; Tregenza, Nick; Cunningham, Andrew A; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06:30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a "two-stage process" where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID:23646103

  11. [Various sides of influenza, part I--structure, replication, changeability of influenza viruses, clinical course of the disease, immunological response and laboratory diagnostics].

    PubMed

    Machała, Magdałena K; Brydak, Lidia Bernadeta

    2006-09-01

    Influenza viruses represent Orthomyxoviridae family. Spherical virions are 80-120 nm in diameter and have two-layer lipid envelope. The following proteins are coded by 8 or 7 segments of the single-stranded RNA: nucleoprotein (NP), polymerase PB2, PB1 and PA, member protein--M1 and M2, glycoproteins--hemagglutinin (HA) and neuraminidase (NA). HA and NA form spikes on the virion surface. On the basis of antigenic differences there are distinguished three types of influenza virus-A, B and C. Besides, influenza A viruses occur in different subtypes, depending on the features of HA and NA. One of influenza characteristics is its antigenic changeability: antigenic drift and antigenic shift. Infection occurs by droplet route, sometimes through direct contact with infected person or surface. Influenza virus attacks epithelial cells of upper respiratory tract, where replication takes place resulting in the production of approximately 1000 of progeny virions during a single 6-12 h cycle in one cell. Necrosis of ciliary cells of mucosa facilitates invasion of bacterial pathogens. Incubation period lasts on average 1-2 days. Influenza illness without complications characterizes the sudden onset of respiratory symptoms and systemic symptoms. Regression of symptoms usually occurs after 3-5 days, but cough and malaise may be observed for over 2 weeks. Reasons for the severe course of the disease or even death are post-influenza complications, e.g. viral pneumonia and bronchitis, bronchiolitis in children, secondary bacterial pneumonia, otitis media, myocarditis and pericarditis, Reye's syndrome, myositis, myoglobinuria, neurological complications and exacerbation of existing chronic diseases. In the case of influenza there is no possible to make the unquestionable diagnosis only on the basis of clinical picture of the disease. Therefore in some circumstances there is important to make some diagnostic laboratory tests as RT-PCR, immunofluorescence assay or isolation of virus and