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 masquerading as acute rejection in a renal allograft recipient with recurrent post transplant diabetic nephropathy.

    PubMed

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh

    2014-08-01

    Rhabdomyolysis contributes to 7-10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases.

  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. 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.

  5. 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

  6. Influence of body mass loss and myoglobinuria on the development of muscle fatigue after a marathon in a warm environment.

    PubMed

    Del Coso, Juan; Salinero, Juan José; Abián-Vicen, Javier; González-Millán, Cristina; Garde, Sergio; Vega, Pablo; Pérez-González, Benito

    2013-03-01

    The aim of this study was to determine the changes in body mass and myoglobinuria concentration in recreational runners during a marathon in a warm environment, and the relation of these changes to muscle fatigue. We recruited 138 amateur runners (114 men and 24 women) for the study. Before the race, leg muscle power output was measured during a countermovement jump on a force platform, body weight was measured, and a urine sample was obtained. Within 3 min of race completion (28 °C; 46% relative humidity), the runners repeated the countermovement jump, body weight was measured again, and a second urine sample was obtained. Myoglobin concentration was determined in the urine samples. After the race, mean body mass reduction was 2.2% ± 1.2%. Fifty-five runners (40% of the total) reduced their body mass by less than 2%, and 10 runners (7.2%) reduced their body mass by more than 4%. Only 3 runners increased their body mass after the marathon. Mean leg muscle power reduction was 16% ± 10%. Twenty-four runners reduced their muscle power by over 30%. No myoglobin was detected in the prerace urine specimens, whereas postrace urinary myoglobin concentration increased to 3.5 ± 9.5 μg·mL(-1) (p < 0.05). Muscle power change after the marathon significantly correlated with postrace urine myoglobin concentration (r = -0.55; p < 0.001), but not with body mass change (r = -0.08; p = 0.35). After a marathon in a warm environment, interindividual variability in body mass change was high, but only 7% of the runners reduced their body mass by more than 4%. The correlation between myoglobinuria and muscle power change suggests that muscle fatigue is associated with muscle breakdown.

  7. [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

  8. 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

  9. 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

  10. 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

  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. HIV-related neuromuscular diseases: nemaline myopathy, amyotrophic lateral sclerosis and bibrachial amyotrophic diplegia.

    PubMed

    Rowland, L P

    2011-06-01

    The human immunodeficiency virus (HIV) causes diverse disorders of the brain, spinal cord and peripheral nerves. Rarely, polymyositis and myoglobinuria are seen. Two other neuromuscular syndromes in people with HIV antibodies are nemaline myopathy and bibrachial amyotrophic diplegia, a form of motor neuron disease. The associations between these diseases and the possibility that HIV infection could be a risk factor for either amyotrophic lateral sclerosis (ALS) itself or other motor neuron diseases are investigated. PMID:21842590

  13. PubMed Central

    ROWLAND, L.P.

    2011-01-01

    SUMMARY The human immunodeficiency virus (HIV) causes diverse disorders of the brain, spinal cord and peripheral nerves. Rarely, polymyositis and myoglobinuria are seen. Two other neuromuscular syndromes in people with HIV antibodies are nemaline myopathy and bibrachial amyotrophic diplegia, a form of motor neuron disease. The associations between these diseases and the possibility that HIV infection could be a risk factor for either amyotrophic lateral sclerosis (ALS) itself or other motor neuron diseases are investigated. PMID:21842590

  14. Non-traumatic acute rhabdomyolysis.

    PubMed

    Taly, A B; Nair, K P; Arunodaya, G R; Das, S; Christopher, R; Mohan, C; Swamy, H S

    1999-03-01

    A boy developed sudden severe generalized muscle stiffness, bulbar weakness and passed dark coloured urine. Laboratory tests revealed marked elevation of creatinine kinase(CK) levels and myoglobinuria. Histopathology of quadriceps muscle showed features of acute rhabdomyolysis. Patient made complete clinical recovery over a period of three weeks and CK returned to normal level. The possible aetiologies of non-traumatic rhabdomyolysis are discussed and the relevant literature reviewed. PMID:10339709

  15. 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

  16. [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.

  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).

  18. Diver with decompression injury, elevation of serum transaminase levels, and rhabdomyolysis.

    PubMed

    Shank, E S; Muth, C M

    2001-05-01

    A 43-year-old female recreational scuba diver presented to the emergency department 1 hour after a rapid, uncontrolled ascent. Her presentation included progressing confusion, slow and slurred speech, and complaints of headache and hypesthesia over her forearms and anterior thighs bilaterally. Differential diagnosis included arterial gas embolism and decompression sickness. She underwent recompression therapy with US Navy Table 6 within 120 minutes of her ascent. After recompression therapy, the patient had signs and symptoms consistent with severe rhabdomyolysis, including creatine kinase levels of 36,000 U/L and myoglobinuria.

  19. Suspected tremetol poisoning in horses.

    PubMed

    Olson, C T; Keller, W C; Gerken, D F; Reed, S M

    1984-11-01

    Of 10 horses in a heavily overgrazed pasture, 4 died within 1 week. Clinical signs included muscle tremors, ataxia, reluctance to walk, heavy sweating, and myoglobinuria. Serum creatine kinase, aspartate transaminase, and alkaline phosphatase activities were high. Histopathologic findings were nonspecific. On the basis of clinical signs, clinicopathologic findings, nonspecific histopathologic findings, the condition of the pasture, the identification of numerous white snakeroot plants from which trematone was extracted, and evidence that these plants had been heavily browsed, it was believed that the horses died from ingestion of Eupatorium rugosum. PMID:6542560

  20. [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

  1. Severe rhabdomyolysis secondary to adenovirus infection: case report and literature review.

    PubMed

    Tseytlin, Daniel; Maynard, Sharon

    2016-04-01

    A 38-year-old male presented with renal failure in the setting of a flu-like illness. Urinalysis showed myoglobinuria and granular casts. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume resuscitated with normal saline and bicarbonate-containing fluid. Workup included a respiratory viral panel which was positive for adenovirus. Other causes such as trauma, seizure, and intoxicants were excluded. He developed progressive renal failure necessitating hemodialysis. After ~ 4 weeks he recovered renal function and dialysis was discontinued. Viral-induced myopathy should be suspected in patients who present with rhabdomyolysis. PMID:26857631

  2. Three instructive cases of tiger snake (Notechis scutatus) envenomation--and how a radioimmunoassay proved the diagnosis.

    PubMed

    Sutherland, S K; Coulter, A R

    1977-08-01

    Three unusual cases are described, in which, in separate incidents, young snake bite victims were found comatose. Tiger snake vemon was detected by radioimmunoassay in the urine and serum, and in one case on the clothing of these children. Gross myoglobinuria was present in all cases. The three cases demonstrate clearly the myolytic potential of tiger snake venom if specific treatment (administration of antivenom) is delayed. Extreme elevation of serum enzyme levels was found in the two victims who survived. Evidence was obtained that the major neurotoxin of tiger snake venom is absorbed at least partly via the lymphatics and that some is excreted in the urine. PMID:904526

  3. Severe rhabdomyolysis without renal injury associated with lightning strike.

    PubMed

    Navarrete, Norberto; Aldana, Norberto Navarrete

    2013-01-01

    Lightning strikes cause injuries in multiple systems and organs. Early recognition of lightning injury syndromes and anticipation of harmful complications can improve outcomes for these patients. The author has presented a case report of a patient who was struck by lightning and exhibited extensive soft tissue injury with myoglobinuria. He was treated with delayed fasciotomy and had evidence of severe muscle injury with markedly elevated creatine kinase levels that gradually improved with aggressive fluid infusion. The patient did not require alkalinization of urine, mannitol, or dialysis, and his renal function remained normal.

  4. 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

  5. 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

  6. [McArdle disease presenting with rhabdomyolisis and acute kidney injury].

    PubMed

    Costa, Rui; Castro, Rui; Costa, Alexandre; Taipa, Ricardo; Vizcaíno, Ramon; Morgado, Teresa

    2013-01-01

    McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.

  7. 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

  8. 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

  9. 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.

  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. 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

  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. Emotionally-intense situations can result in rhabdomyolysis in McArdle disease

    PubMed Central

    Brady, Stefen; Godfrey, Richard; Scalco, Renata S; Quinlivan, Ros M

    2014-01-01

    Despite the majority of patients with McArdle disease reporting symptoms including fatigue, cramps and episodes of myoglobinuria from early childhood, diagnosis is often delayed by several decades. Additionally, many individuals with rhabdomyolysis remain undiagnosed. The occurrence of symptoms during exercise, particularly isometric muscle contraction such as heavy lifting, is well known in McArdle disease. However, isometric muscle contraction that occurs with emotion is not recognised as exercise and may be missed as a trigger for rhabdomyolysis, potentially leading to a delay in diagnosis. Three patients are presented here, all with symptoms from childhood including episodes of rhabdomyolysis induced by tense emotional situations without physical exertion; two patients reported recurrent episodes while watching rather than playing football. The remaining patient developed rhabdomyolysis during a heated argument. These patients’ histories emphasise the risk from sustained isometric muscle contraction that occurs in emotive situations for patients with McArdle disease. PMID:25293680

  14. 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

  15. 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

  16. Rhabdomyolysis Induced by Nonstrenuous Exercise in a Patient with Graves' Disease

    PubMed Central

    Summachiwakij, Sarawut

    2014-01-01

    Hyperthyroidism can result in several musculoskeletal conditions such as thyrotoxic periodic paralysis, thyrotoxic myopathy, and thyroid ophthalmopathy. Rhabdomyolysis has been rarely reported to be associated with hyperthyroidism. We describe a 33-year-old man who presented with bilateral thigh pain and dark brown urine after regular squatting. He had a past medical history of hyperthyroidism but stopped taking it 2 months prior to admission. He was found to have rhabdomyolysis, myoglobinuria, and thyrotoxicosis. Presence of thyroid-stimulating immunoglobulins (TSI) and high radioiodine uptake confirmed a diagnosis of Graves' disease. He received aggressive fluid resuscitation and sodium bicarbonate intravenously along with monitoring fluid and electrolyte. Methimazole was also resumed. The patient responded to treatment and rhabdomyolysis gradually resolved. Therefore, nonstrenuous exercise can potentially induce rhabdomyolysis in patients with hyperthyroidism. Although hyperthyroidism is not widely recognized as a cause of rhabdomyolysis, it should be considered in the differential diagnosis of rhabdomyolysis. PMID:24716006

  17. Drug-related Myopathies of Which the Clinician Should Be Aware

    PubMed Central

    Valiyil, Ritu

    2011-01-01

    Many drugs used for therapeutic interventions can cause unanticipated toxicity in muscle tissue, often leading to considerable morbidity. A drug-induced, or toxic, myopathy is defined as the acute or subacute manifestation of myopathic symptoms such as muscle weakness, myalgia, creatine kinase elevation, or myoglobinuria that can occur in patients without muscle disease when they are exposed to certain drugs. A brief review of agents with a known association with myotoxicity and the proposed mechanisms linked to that toxicity is outlined; however, the purpose of this review is to highlight recent discoveries and advances in the field of toxic myopathies that have practical implications for practicing physicians. Because many drug-related myopathies are potentially reversible at early stages, it is important for clinicians to recognize toxic myopathies early in their course to determine when to discontinue therapy and potentially prevent irreversible muscle damage. PMID:20425521

  18. Acute renal failure due to traumatic rhabdomyolysis.

    PubMed

    Naqvi, R; Akhtar, F; Yazdani, I; Hafiz, S; Zafar, N; Naqvi, A; Rizvi, A

    1995-03-01

    Trauma and non-traumatic insults can cause muscle damage to such an extent that serious sequelae to other organs may result. Myoglobinuria and subsequent acute renal failure (ARF) is a well known and widely studied fact of such sequelae. Twelve cases of ARF (between 1990-1993) who have developed renal dysfunction after prolonged muscular exercise e.g., squat jumping, sit-ups and blunt trauma from sticks or leather belts mainly given by law enforcing personnel for certain issues were studied. None of them had previous history of myopathy, neuropathy or renal disease. All were critically ill on presentation and required renal support in the form of dialysis. Although morbidity was high in all, eleven of them recovered and one expired due to sepsis.

  19. 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

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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

  5. 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

  6. 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

  7. [Suspected case of postoperative malignant hyperthermia treated with dantrolene one week after neurosurgery].

    PubMed

    Itoh, Kazushi; Nishibe, Shinichi; Usuda, Yutaka; Kitamura, Akira

    2014-10-01

    We report the case of a 16-year-old man who presented with hyperthermia (>40°C), an elevated creatine kinase level (>64,000 IU · l-1), and myoglobinuria one week after undergoing two successive neurosurgeries for a brain hemorrhage under sevoflurane anesthesia. After having been diagnosed with suspicious atypical postoperative malignant hyperthermia, he was treated with dantrolene and his symptoms disappeared on the day of dantrolene administration. Central hyperthermia is defined as hyperthermia associated with thermoregulatory dysfunction after brainstem injury. Postoperative malignant hyperthermia can sometimes be difficult to distinguish from central hyperthermia, especially after neurosurgery. We could not eliminate the possibility of central hyperthermia as a cause of hyperthermia in the present patient If marked postoperative hyperthermia must be addressed immediately and managed appropriately in neurosurgical patients and dantrolene having few serious side effects, we were able to control his symptoms immediately after the infusion of dantrolene. Therefore, the administration of dantrolene should be considered when treating unidentified postoperative hyperthermia after a neurosurgical procedure. PMID:25693350

  8. 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.

  9. 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

  10. 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

  11. 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

  12. McArdle disease: what do neurologists need to know?

    PubMed

    Lucia, Alejandro; Nogales-Gadea, Gisela; Pérez, Margarita; Martín, Miguel A; Andreu, Antoni L; Arenas, Joaquín

    2008-10-01

    McArdle disease (also known as glycogen storage disease type V) is a pure myopathy caused by an inherited deficit of myophosphorylase, the skeletal muscle isoform of the enzyme glycogen phosphorylase. The disease exhibits clinical heterogeneity, but patients typically experience exercise intolerance, that is, reversible, acute crises (early fatigue and contractures, sometimes with rhabdomyolysis and myoglobinuria) triggered by static muscle contractions (e.g. lifting weights) or dynamic exercise (e.g. climbing stairs or running). In this Review, we discuss the main features of McArdle disease, with the aim of providing neurologists with up-to-date, useful information to assist their patients. The topics covered include diagnostic tools-for example, molecular genetic diagnosis, the classic ischemic forearm test and the so-called 'second wind' phenomenon-and current therapeutic options-for example, a carbohydrate-rich diet and carbohydrate ingestion shortly before strenuous exercise, in combination with medically supervised aerobic training of low to moderate intensity.

  13. 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

  14. Malignant hyperthermia in a halothane-anesthetized horse.

    PubMed

    Waldron-Mease, E; Klein, L V; Rosenberg, H; Leitch, M

    1981-11-01

    Malignant hyperthermia developed in a 4-year-old Thoroughbred horse following 3 hours and 15 minutes of halothane anesthesia, with supplementary succinylcholine. Clinical signs included fever, sweating, hyperventilation, tachycardia, and decreased blood pressure followed by a rapid increase in blood pressure. Biochemical aberrations included hypocalcemia, hyperkalemia, hyperphosphatemia, myoglobinuria, and high creatine phosphokinase and ornithine carbamyl transferase activities. Treatment consisted initially of surface cooling with cold water, alcohol and ice, IV administration of cooled balanced electrolyte solutions and sodium bicarbonate, and removal from the anesthetic and rebreathing circuit. Oxygen was given by endotracheal insufflation. The rectum was then packed with ice, the horse was moved to a recovery raft and pool, and his body was packed in ice. Xylazine and dantrolene were given during recovery from anesthesia. Following recovery, treatment consisted of administration of balanced electrolyte solutions, calcium borogluconate, potassium penicillin, meperidine, and additional dantrolene. Muscle biopsy demonstrated exaggerated contracture responses to halothane and caffeine, confirming a diagnosis of malignant hyperthermia. The horse was returned to training following a routine postsurgical convalescent period.

  15. Mechanisms of exertional fatigue in muscle glycogenoses.

    PubMed

    Vissing, John; Haller, Ronald G

    2012-12-01

    Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis, which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue. PMID:23182633

  16. Crush syndrome chez l’adulte et problematique de sa prise en charge a la phase aiguë

    PubMed Central

    Hemou, P.F.; Sama, H.D.; Tchétikè, P.; Potkar, T.

    2015-01-01

    Summary Crush syndrome is defined as the local and systemic response to a traumatic rhabdomyolysis caused by compartment syndrome (prolonged compression of a large muscle mass leading to ischemia). It is not usually an isolated event, and may go unnoticed in the first 24 to 48 hours of a severe polytrauma. Ignored crush syndrome can lead to acute renal failure secondary to myoglobinuria occurring in a hypovolemic patient, with acidosis and hyperkalaemia. Crush syndrome is a medical and surgical emergency, frequently occurring after disasters such as earthquakes or major explosions with collapse of buildings. The acute revascularization syndrome that can occur after decompression (either surgical, or removing the weight from the crushed body part or removing a tourniquet) can cause irreversible cardiac arrest due to acute hyperkalaemia and hypovolemia. Early fluid resuscitation (starting pre-hospital and lasting over the first 24 hours) is crucial to restore and maintain normovolemia, and a urine output of 1-2ml/kg/hour is recommended during the first 24 hours. Diuretics may help to maintain this high urine output, and preventing tubular precipitate of myoglobin in acidic urine via bicarbonate may be useful. Early nutrition targets may be obtained using early “prophylactic” haemodialysis. PMID:27777548

  17. PYGM expression analysis in white blood cells: a complementary tool for diagnosing McArdle disease?

    PubMed

    de Luna, Noemí; Brull, Astrid; Lucia, Alejandro; Santalla, Alfredo; Garatachea, Nuria; Martí, Ramon; Andreu, Antoni L; Pinós, Tomàs

    2014-12-01

    McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence of myophosphorylase activity in skeletal muscle biopsies and genetic analysis of the myophosphorylase-encoding gene, PYGM. The recently reported association between myophosphorylase and Rac1 GTPase in a T lymphocyte cell line prompted us to study myophosphorylase expression in white blood cells (WBCs) from 20 healthy donors and 30 McArdle patients by flow cytometry using a fluorescent-labeled PYGM antibody. We found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001). PYGM mRNA levels were also lower in white blood cells from McArdle patients. Nevertheless, in 13% of patients (who were either heterozygotes or homozygotes for the most common PYGM pathogenic mutation among Caucasians (p.R50X)), the percentage of myophosphorylase-positive white blood cells was not different compared with the control group. Our findings suggest that analysis of myophosphorylase expression in white blood cells might be a useful, less-invasive, complementary test for diagnosing McArdle disease.

  18. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2009-2013.

    PubMed

    2014-03-01

    Among active component U.S. service members in 2013, there were 378 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress (exertional rhabdomyolysis). The annual incidence rates of exertional rhabdomyolysis increased 33 percent during 2009-2013. In 2013, the highest incidence rates occurred in service members who were male; younger than 20 years of age; either Asian/Pacific Islander or black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Incidence rates were higher among service members with homes of record from the Northeast compared to other regions of the United States. 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:24684616

  19. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2010-2014.

    PubMed

    2015-03-01

    Among active component U.S. service members in 2014, there were 403 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Th e annual incidence rates of exertional rhabdomyolysis increased nearly 50% during 2010–2014. In 2014, 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. Incidence rates were higher among service members with homes of record from the Northeast compared to other U.S. regions. 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)aft er strenuous physical activity, particularly in hot, humid weather. PMID:25825932

  20. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces 2008-2012.

    PubMed

    2013-03-01

    In 2012, there were 402 incident episodes of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis") among U.S. service members. The annual rates of exertional rhabdomyolysis increased 30 percent from 2008 to 2012. Th e highest incidence rates occurred in males, black, non-Hispanic service members, service members younger than 20 years of age, members of the Army and Marine Corps, recruit trainees, and those in combat-specific occupations. Incidence rates were higher among service members with homes of record from the Northeast compared to other regions of the U.S. Most cases were diagnosed at installations that support basic combat/recruit training or major Army or Marine Corps ground combat units. 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, and/or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather. PMID:23550931

  1. Hemoglobinuria Misidentified as Hematuria: Review of Discolored Urine and Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Veerreddy, Prashant

    2013-01-01

    Discolored urine is a common reason for office visits to a primary care physician and urology referral. Early differentiation of the type or cause of discolored urine is necessary for accurate diagnosis and prompt management. Paroxysmal nocturnal hemoglobinuria is a clonal disorder caused by acquired somatic mutations in the PIG-A gene on the X- chromosome of hemopoietic stem cells and leads to deficiency of surface membrane anchor proteins. The deficiency of these proteins leads to an increased risk of hemolysis of erythrocytes and structural damage of platelets, resulting in a clinical syndrome characterized by complement-mediated intravascular hemolytic anemia, bone marrow failure, and venous thrombosis. Patients with this clinical syndrome present with paroxysms of hemolysis, causing hemoglobinuria manifesting as discolored urine. This can be easily confused with other common causes of discolored urine and result in extensive urologic work-up. Three commonly confused entities of discolored urine include hematuria, hemoglobinuria, and myoglobinuria. Specific characteristics in a dipstick test or urinalysis can guide differentiation of these three causes of discolored urine. This article begins with a case summary of a woman presenting with cranberry-colored urine and a final delayed diagnosis of paryxysmal nocturnal hemoglobinuria. Her hemoglobinuria was misdiagnosed as hematuria, leading to extensive urologic work-up. The article also gives an overview of the approach to diagnosing and treating discolored urine. PMID:25512715

  2. Toxic and drug-induced myopathies.

    PubMed

    Dalakas, M C

    2009-08-01

    Drugs used for therapeutic interventions either alone or in combination may sometimes cause unexpected toxicity to the muscles, resulting in a varying degree of symptomatology, from mild discomfort and inconvenience to permanent damage and disability. The clinician should suspect a toxic myopathy when a patient without a pre-existing muscle disease develops myalgia, fatigue, weakness or myoglobinuria, temporally connected to the administration of a drug or exposure to a myotoxic substance. This review provides an update on the drugs with well-documented myocytoxicity and cautions the clinicians to be alert for the potential toxicity of newly marketed drugs; highlights the clinical features and pathomechanisms of the induced muscle disease; and offers guidance on how best to treat and distinguish toxic myopathies from other acquired or hereditary muscle disorders. Practical issues regarding the diagnosis and management of statin-induced myopathies are emphasized. Myotoxicity resulting from direct insertion of transgenes to the muscle, an exciting new tool currently tested for treatment of muscular dystrophies, is also discussed.

  3. 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

  4. PubMed Central

    TAGLIA, ANTONELLA; PETILLO, ROBERTA; D'AMBROSIO, PAOLA; PICILLO, ESTHER; TORELLA, ANNALAURA; ORSINI, CHIARA; ERGOLI, MANUELA; SCUTIFERO, MARIANNA; PASSAMANO, LUIGIA; PALLADINO, ALBERTO; NIGRO, GERARDO

    2015-01-01

    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

  5. [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.

  6. Coexistence of VHL Disease and CPT2 Deficiency: A Case Report

    PubMed Central

    Ferrara, Alfonso Massimiliano; Sciacco, Monica; Zovato, Stefania; Rizzati, Silvia; Colombo, Irene; Boaretto, Francesca; Moggio, Maurizio; Opocher, Giuseppe

    2016-01-01

    von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations. PMID:27034144

  7. 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

  8. 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

  9. 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

  10. Acute exercise-induced bilateral thigh compartment syndrome.

    PubMed

    Boland, Michael R; Heck, Chris

    2009-03-01

    Acute compartment syndrome of the thigh is rare due to the space's ability to accommodate large volumes of fluid and, with the exception of the lateral septum, its thin compliant linings. This article describes a case of bilateral exercise-induced severe compartment syndrome treated with anterior and posterior fasciotomies. A 29-year-old man was admitted to intensive care with myoglobinuria. His left thigh was evaluated 18 hours later for compartment syndrome. The patient reported that 14 hours prior to initial presentation, he had participated in a 1-hour session of vigorous basketball. He gradually developed bilateral moderately severe thigh pain and tea-colored urine. Physical examination revealed pain secondary to passive stretch of both knees at 20 degrees flexion, plus firm anterior and posterior compartments to palpation. A handheld pressure monitor revealed the following compartment pressures: left anterior 80 mm Hg; left posterior 75 mm Hg; right anterior 45 mm Hg; and right posterior 50 mm Hg. Bilateral emergent anterior and posterior compartment fasciotomies were performed. The patient developed a significant severe distal motor and sensory neurological deficit on the left side, which recovered to 3/5 motor strength and protective sensation. At 6-month follow-up, he ambulated with the assistance of a left ankle foot orthosis. Acute severe compartment syndrome can occur following vigorous exercise. We recommend fasciotomies after exercise-induced acute compartment syndrome rather than initial observation because of the severity of morbidity associated with undertreated compartment syndrome.

  11. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).

    PubMed

    Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

    2014-01-01

    Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D

  12. Rhabdomyolysis in Critically Ill Surgical Patients

    PubMed Central

    Kuzmanovska, Biljana; Cvetkovska, Emilija; Kuzmanovski, Igor; Jankulovski, Nikola; Shosholcheva, Mirjana; Kartalov, Andrijan; Spirovska, Tatjana

    2016-01-01

    Introduction: Rhabdomyolysis is a syndrome of injury of skeletal muscles associated with myoglobinuria, muscle weakness, electrolyte imbalance and often, acute kidney injury as severe complication. The aim: of this study is to detect the incidence of rhabdomyolysis in critically ill patients in the surgical intensive care unit (ICU), and to raise awareness of this medical condition and its treatment among the clinicians. Material and methods: A retrospective review of all surgical and trauma patients admitted to surgical ICU of the University Surgical Clinic “Mother Teresa” in Skopje, Macedonia, from January 1st till December 31st 2015 was performed. Patients medical records were screened for available serum creatine kinase (CK) with levels > 200 U/l, presence of myoglobin in the serum in levels > 80 ng/ml, or if they had a clinical diagnosis of rhabdomyolysis by an attending doctor. Descriptive statistical methods were used to analyze the collected data. Results: Out of totally 1084 patients hospitalized in the ICU, 93 were diagnosed with rhabdomyolysis during the course of one year. 82(88%) patients were trauma patients, while 11(12%) were surgical non trauma patients. 7(7.5%) patients diagnosed with rhabdomyolysis developed acute kidney injury (AKI) that required dialysis. Average values of serum myoglobin levels were 230 ng/ml, with highest values of > 5000 ng/ml. Patients who developed AKI had serum myoglobin levels above 2000 ng/ml. Average values of serum CK levels were 400 U/l, with highest value of 21600 U/l. Patients who developed AKI had serum CK levels above 3000 U/l. Conclusion: Regular monitoring and early detection of elevated serum CK and myoglobin levels in critically ill surgical and trauma patients is recommended in order to recognize and treat rhabdomyolysis in timely manner and thus prevent development of AKI. PMID:27703296

  13. 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.

  14. Ultrastructural alterations in skeletal muscle of pigs with acute monensin myotoxicosis.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1984-01-01

    Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:6696050

  15. Acute renal failure due to non-traumatic rhabdomyolysis

    PubMed Central

    Chugh, K. S.; Nath, I. V. S.; Ubroi, H. S.; Singhal, P. C.; Pareek, S. K.; Sarkar, A. K.

    1979-01-01

    Seventeen patients with acute renal failure of diverse aetiology showed myoglobinuria and elevated levels of serum creatine phosphokinase (mean 119·2 Sigma u./ml) and adolase (mean 88·5 Sibley-Lehninger (SL)u./ml), indicating the presence of diffuse muscle cell injury. The primary conditions which led to rhabdomyolysis and acute renal failure were burns, eclampsia, prolonged labour, crush injury, epileptiform convulsions, status asthmaticus, viral myositis and intoxication with chemicals including copper sulphate, mercuric chloride and zinc phosphide. In 10 non-myoglobinuric patients with acute renal failure, serum creatine phosphokinase was normal (mean 8·9 Sigma u./ml) and serum aldolase was only slightly elevated (mean 11·2 SL u./ml). Although uric acid was elevated in both groups, the values were significantly higher in myoglobinuric (mean 0·728 ± 0·199 mmol/l) compared to non-myoglobinuric patients (mean 0·583 ± 0·093 mmol/l). During the oliguric phase, hypocalcaemia was observed in 82·2% of myoglobinuric patients and in 20% of non-myoglobinuric patients. Ten out of 15 patients with myoglobinuric renal failure developed hypercalcaemia during the diuretic phase whereas only 3 non-myoglobinuric patients showed a transient hypercalcaemia. Although the mean serum potassium was somewhat higher in the myoglobinuric patients, the difference between the 2 groups was not significant. It is concluded that acute renal failure associated with non-traumatic rhabdomyolysis is not infrequent and may occur in a variety of conditions where gross evidence of muscle injury is lacking. PMID:482182

  16. 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.

  17. 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

  18. 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