Disease relevance of Myoglobinuria

• This defect may be a common cause of elevated serum creatine kinase levels, as seen in the patient described here and of unexplained episodes of rhabdomyolysis and myoglobinuria [1].
• All patients had serum creatine kinase levels of more than 10,000 U/L, 4 tested showed myoglobinuria, and 5 had acute renal failure [2].
• Patients typically had early marked increase and rapid decrease of serum aminotransferases, mild-to-moderate increase in prothrombin time, myoglobinuria, and moderate azotemia [3].
• Five patients who had injected intravenous (i.v.) phenmetrazine or methamphetamine developed marked prostration resembling septic shock, disseminated intravascular coagulation, rhabdomyolysis with myoglobinuria, and azotemia [4].
• It is not certain whether a genetic myopathy made these brothers susceptible to viral-induced myoglobinuria, but a normal response of venous lactate to ischemic work excluded lack of phosphorylase or phosphofructokinase as a cause of the myoglobinuria in the surviving brother [5].

Psychiatry related information on Myoglobinuria

• Less common, but more striking, illnesses attributed to substance abuse include ATM, a subacute myeloradiculoneuropathy resembling combined systems disease, Guillain-Barré syndrome, plexitis, fulminant axonal neuropathy, and acute myoglobinuria with or without severe weakness [6].

High impact information on Myoglobinuria

• We have identified a 15-bp microdeletion in a highly conserved region of the mitochondrially encoded gene for cytochrome c oxidase (COX) subunit III in a patient with severe isolated COX deficiency and recurrent myoglobinuria [7].
• Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients [8].
• Clofibrate-induced muscle damage with myoglobinuria and cardiomyopathy [9].
• Letter: Karate myoglobinuria [10].
• Myoglobinuria following aminocaproic acid administration [11].

Chemical compound and disease context of Myoglobinuria

• Recently, we described a patient with severe exercise intolerance and episodic myoglobinuria, associated with marked impairment of succinate oxidation and deficient activity of succinate dehydrogenase and aconitase in muscle mitochondria (1) [12].
• Recurrent myoglobinuria due to muscle carnitine palmityl transferase deficiency [13].
• We conclude that nontraumatic myoglobinuria with acute renal failure is not infrequent and may occur after an overdose of ethanol or heroin [14].
• Muscle PGK deficiency is now added to two other newly recognized glycolytic defects, phosphoglycerate mutase and lactate dehydrogenase deficiencies, as a cause of recurrent myoglobinuria [15].
• We report on a 16-year-old girl with short-chain L-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase deficiency resulting in juvenile-onset recurrent myoglobinuria, hypoketotic hypoglycemic encephalopathy, and hypertrophic/dilatative cardiomyopathy [16].

Biological context of Myoglobinuria

• RESULTS: Linkage analysis of markers in the 18qter region, where we previously had located the CCFDN gene, produced a lod score of 3.55, demonstrating colocalization of the gene responsible for MSS with demyelinating neuropathy and myoglobinuria with the CCFDN gene [17].
• The molecular abnormality of a phosphoglycerate kinase variant which was associated with severe tissue enzyme deficiency and episodes of muscle contractions and myoglobinuria was examined [18].
• In a patient with symptoms and signs of exercise intolerance and myoglobinuria we originally ascribed pathogenicity to a mitochondrial-tRNA(Phe) mutation but here we show that the true pathogenic mutation was a novel mutation in the gene encoding subunit II of cytochrome c oxidase [19].
• We have identified a novel missense mutation in the carnitine palmitoyltransferase II (CPT II) gene in a child with CPT II deficiency characterized clinically by episodes of myalgia and myoglobinuria induced by intercurrent febrile illnesses [20].
• Another respiratory chain defect, primary coenzyme Q10 (CoQ10) deficiency, also causes exercise intolerance and recurrent myoglobinuria, usually in conjunction with brain symptoms, such as seizures or cerebellar ataxia [21].

Anatomical context of Myoglobinuria

• After the onset of recurrent myoglobinuria when she was 16 years old, deficiency of carnitine palmitoyltransferase type II (32% residual activity) was diagnosed on the basis of cultured skin fibroblasts [22].
• In the second category, patients usually present with muscle cramps on exertion then followed by myoglobinuria without established proximal myopathy and their symptoms are associated with deficiency of carnitine palmityl transferase in skeletal muscle [23].
• Clinically, a large number of PM patients with eosinophils manifested an acute- or subacute-onset of symptoms, myoglobinuria, a marked elevation of serum creatine kinase, a good response to steroid therapy, and a relatively benign course compared with 26 PM patients without eosinophils [24].
• Skin biopsy showed a strong dystrophin reaction in the arrector pili muscles and in the myoepithelial cells of the sweat glands of patients with congenital muscular dystrophy, polymyositis, distal myopathy, putative Duchenne muscular dystrophy carriers, myoglobinuria, neurogenic atrophy and in a normal control [25].
• Surface electromyograms were used to evaluate the muscle spasm theory; the possibility of actual muscle cell damage was monitored by the presence of myoglobinuria, while the ratio of hydroxyproline/creatinine (OHP/Cr) in 24 hr urine collection was used as a marker for connective tissue involvement [26].

Gene context of Myoglobinuria

• Thirty patients had specific enzymopathies without myoglobinuria: 14 had phosphorylase deficiency, 9 had MAD deficiency, 3 had phosphorylase kinase deficiency, 3 had PFK deficiency, and 1 had PGAM deficiency [27].
• Combined defects of muscle phosphofructokinase and AMP deaminase in a child with myoglobinuria [28].
• A 15-base pair, in-frame, deletion (9480del15) in the mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit III (COX III) gene was identified previously in a patient with recurrent episodes of myoglobinuria and an isolated COX deficiency [29].
• A 61-year-old woman with muscle phosphofructokinase (PFK) deficiency had mild limb weakness all her life but no cramps or myoglobinuria [30].
• Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria [31].

Analytical, diagnostic and therapeutic context of Myoglobinuria

• Immunodiffusion showed the presence of myoglobin in the urine (myoglobinuria) of experimental animals [32].
• We conclude that deficiency of carnitine palmitoyltransferase type II may be a cause of pancreatitis and should be considered in the differential diagnosis, even in the absence of overt myoglobinuria [22].
• Agarose gel electrophoresis was found to be an excellent method for the investigation of myoglobinuria since this technique not only allowed the separation of myoglobin from hemoglobin but also myoglobin from metmyoglobin [33].
• It may result in myoglobinuria, the filtration of myoglobin into the urine, and is often associated with acute renal failure (ARF) [34].

References