Primary myoglobinuria and exercise-induced secondary myoglobinuria: a report of 7 cases seen at an army basic training center.
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Hemoglobinuria↗
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Early predictors of myoglobinuria and acute renal failure following electrical injury.
Myoglobinuria-induced acute renal failure (ARF) is a potentially lethal consequence of electrical injury. We describe clinical variables that can predict the risk of myoglobinuria and ARF following electrical injury. This was a retrospective multivariate analysis of risk factors among electrically injured patients over a 26-year period. Urine myoglobin status was documented in 162 patients; 14% had myoglobinuria. No patient developed ARF. Multivariate modeling revealed that high-voltage exposure, prehospital cardiac arrest, full-thickness burns, and compartment syndrome were associated with myoglobinuria. Using a prediction rule defined as positive when a patient had > or = 2 risk factors yielded a sensitivity of 96% and negative predictive value of 99%. Electrical injury patients with myoglobinuria have little risk of developing ARF. A prediction rule can be used to screen out patients at low risk for myoglobinuria and identify high-risk patients who warrant early aggressive treatment and a more definitive myoglobin test.
Acute Kidney Injury↗
The incidence of myoglobinuria in patients with pneumatic trousers.
The possible association between the use of pneumatic trousers and myoglobinuria was investigated. One hundred and four victims of multiple trauma were entered into a study over a three-month period. Patients who suffered serious injuries to two or more organ systems qualified for entrance into the study. Patients who arrived at the emergency department with inflated pneumatic trousers served as the test population (n = 50), and patients who did not have pneumatic trousers served as the controls (n = 54). Urine specimens were obtained from all patients just before the completion of their treatment in the emergency department. No patients in the control group had myoglobinuria 0%), and only one patient in the test group had myoglobinuria 2%). The results were not statistically significant. Myoglobinuria is not an acute complication of the use of pneumatic trousers. The presence of pneumatic trousers on a multiple-trauma patient is not an indication for routine screening for myoglobinuria in the emergency department.
Adult↗
Physiologic amputation prevents myoglobinuria from lower extremity myonecrosis.
Myoglobinuria secondary to myonecrosis is a proven cause of renal failure, especially in critically ill patients. Physiologic amputation or cryoamputation has been used at our institution for the past two decades as a safe and effective treatment for lower extremity infection, intractable rest pain, and irreversible myonecrosis. We retrospectively studied five critically ill patients with myonecrosis of lower extremities associated with myoglobinuria. The etiology of myonecrosis included preexisting peripheral vascular disease or crush injury to the lower extremities. It was determined that all five patients were too ill to undergo emergency amputation. Myoglobinuria was documented in all five patients and cleared within 24 hours of physiologic amputation in four patients. All five patients had elevated creatine phosphokinase levels (mean 20,270 mU/mL, range 12,090 to 43,164 mU/mL) that significantly decreased within 48 hours of physiologic amputation (mean 6,488 mU/mL, range 2,250 to 13,580 mU/mL). Mechanical ventilation and cardiovascular support were required in four patients. All patients had transient episodes of renal insufficiency with two progressing to anuric renal failure and requiring dialysis. One patient's renal failure resolved after 56 days, but the other patient died of a cerebrovascular accident 22 days after initiation of physiologic amputation. The mean duration of physiologic amputation was 15.6 days (range 5 to 32 days) with no significant complication due to physiologic amputation. All five patients had surgical amputation successfully. Three patients survived. The two deaths in the study were due to a cerebrovascular accident in one patient and a cardiopulmonary arrest in another. Physiologic amputation is a treatment option that halts myonecrosis, prevents myoglobinuria, and lessens the risk of associated acute renal failure. Physiologic amputation may be appropriately used in patients with myoglobinuria due to extremity myonecrosis who are deemed too critically ill to survive emergency amputation.
Acute Kidney Injury↗
Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA.
OBJECTIVE: To elucidate the molecular basis of a mitochondrial myopathy associated with recurrent myoglobinuria and cytochrome c oxidase (COX) deficiency in muscle. BACKGROUND: Recurrent myoglobinuria is typically seen in patients with inborn errors of carbohydrate or lipid metabolism, the main sources of energy for muscle contraction. Relatively little attention has been directed to defects of the mitochondrial respiratory chain in patients with otherwise unexplained recurrent myoglobinuria. METHODS: Having documented COX deficiency histochemically and biochemically in the muscle biopsy from a patient with exercise-induced recurrent myoglobinuria, the authors sequenced the three mitochondrial DNA (mtDNA)-encoded COX genes, and performed restriction fragment length polymorphism analysis and single-fiber PCR. RESULTS: The authors identified a nonsense mutation (G5920A) in the COX I gene in muscle mtDNA. The mutation was heteroplasmic and abundantly present in COX-negative fibers, but less abundant or absent in COX-positive fibers; it was not found in blood or fibroblasts from the patient or in blood samples from the patient's asymptomatic mother and sister. CONCLUSIONS: The G5920A mutation caused COX deficiency in muscle, explaining the exercise intolerance and the low muscle capacity for oxidative phosphorylation documented by cycle ergometry. The sporadic occurrence of this mutation in muscle alone suggests that it arose de novo in myogenic stem cells after germ-layer differentiation. Mutations in mtDNA-encoded COX genes should be considered in patients with recurrent myoglobinuria.
Adult↗
Establishment of an animal model for myoglobinuria by use of a myotoxin from Pseudechis australis (king brown snake) venom in mice.
A new laboratory animal model for studying the pathologic mechanisms of myoglobinuria in mice after envenomation with Pseudechis australis snake venom or its myotoxin has been established. The experimental mice (Swiss albino) had myoglobinuria 60 min after administration of the venom, as indicated by red or dark-brown urine. Light microscopic studies revealed myonecrosis of the locally injected soleus muscle 30 min after exposure to the myotoxin, followed by regeneration in 7 to 10 days. Electron microscopic studies of the soleus muscle revealed fragmentation and dissolution of the Z disk, followed by degeneration of the sarcomere. Light microscopy of the kidneys revealed numerous pigmented casts filling the lumen of the tubules; some tubules had features of acute tubular necrosis. Immunohistochemical localization of myoglobin by the immunoperoxidase method confirmed myoglobin casts in the renal tubules. Electron microscopy of the kidneys also revealed intratubular casts composed of markedly electron-dense material filling the lumen. These results indicate that rhabdomyolysis caused by the venom or toxin is followed by myoglobinuria, with renal manifestations in the form of myoglobin cast nephropathy and tubulopathy. This mouse model of experimental snake venom-induced myoglobinuria is an ideal model for investigating the entire sequence of myoglobinuria and related cast nephropathy.
Animals↗
Metabolic causes of myoglobinuria.
To evaluate the proportion of cases of myoglobinuria that can be ascribed to specific metabolic defects, we have studied eight enzymes--phosphorylase, phosphorylase kinase, phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), lactate dehydrogenase (LDH), carnitine palmitoyltransferase (CPT), and myoadenylate deaminase (MAD)--in muscle biopsy specimens from 77 consecutive patients with myoglobinuria (documented in 44, suspected in 33). Enzyme defects were found in 36 patients: CPT deficiency in 17, phosphorylase deficiency in 10, phosphorylase kinase deficiency in 4, MAD deficiency in 3, PGK deficiency in 1, and a combined defect of CPT and MAD in 1. Exercise was the main precipitating factor, both in patients with and in those without detectable enzymopathies. 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. Systematic biochemical evaluation of muscle biopsy specimens revealed specific enzymopathies in about half of the patients with idiopathic myoglobinuria. The rest may have blocks of metabolic pathways not yet studied routinely, such as beta oxidation, or genetic defects of the sarcolemma, such as Becker's muscular dystrophy.
AMP Deaminase↗
Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria.
Markedly reduced cytochrome c oxidase (COX) activity was found in cultured skin fibroblasts of an infant with recurrent episodes of acute myoglobinuria, hypertonia, muscle stiffness and elevated plasma levels of sarcoplasmic enzymes (creatine kinase 96950 U/l, normal below 150) since the age of 3 weeks (COX activity: 36 nmol/min/mg protein; normal 65-440; COX/succinate cytochrome c reductase ratio: 1.4, normal 3.0 +/- 0.4). The expression of the disease in cultured fibroblasts allowed us to carry out a prenatal diagnosis during the next pregnancy. Hitherto, mitochondrial respiratory chain deficiency has not been established as a cause of recurrent myoglobinuria in childhood. Since most cases of myoglobinurias remain poorly understood, we suggest giving consideration to respiratory chain deficiency in elucidating the origin of unexplained recurrent myoglobinuria in childhood, especially when seemingly unrelated symptoms are present.
Blotting, Southern↗
Absence of myoglobinuria in acute psychotic patients with marked elevation in serum creatine phosphokinase level.
Elevated levels of serum creatine phosphokinase, muscular type (CK(MM)) are caused primarily by diseased muscle fiber. Acute psychoses are often associated with a marked increase in serum CK(MM) levels, though the reason remains obscure. Since striated muscle damage is also associated with pigmenturia and myoglobinuria, we sought to determine whether the markedly high serum CK level of acute psychosis reflects skeletal muscle damage by evaluating urinary myoglobin in affected patients. Baseline serum CK was measured on admission in 713 consecutive acute psychotic inpatients (BPRS> or =40). Those showing a serum CK levels above 1000 IU/l on the first 2 days of hospitalization underwent urine collection for myoglobin testing. Patients with physical trauma or medical conditions known to cause CKemia were excluded. Twenty-five patients were eligible for the study. In no case did myoglobinuria or pigmenturia accompany the marked CKemia. There is an unexpected dissociation between the robust increase in the serum CK(MM) levels and the absence of myoglobinuria in acute psychosis. Our negative finding may indicate that the serum CK threshold for myoglobinuria is very high (above 10000 IU/l). Alternatively, psychosis-associated CKemia may be related to an unknown, nontraumatic, pathophysiological mechanism(s).
Acute Disease↗
Respiratory chain deficiency presenting as recurrent myoglobinuria in childhood.
Myoglobinuria is an abnormal urinary excretion of myoglobin due to an acute destruction of skeletal muscle fibres. Several metabolic diseases are known to account for myoglobinuria including defects of glycolysis and fatty acid oxidation. Here, we report on respiratory chain enzyme deficiency in three unrelated children with recurrent episodes of myoglobinuria and muscle weakness (complex I: one patient, complex IV: two patients). All three patients had generalized hyporeflexia during attacks, a feature which is not commonly reported in other causes of rhabdomyolysis. Studying respiratory chain enzyme activities in cultured skin fibroblasts might help diagnosing this condition, especially when acute rhabdomyolysis precludes skeletal muscle biopsy during and immediately after episodes of myoglobinuria.
Acute Disease↗
ECG abnormalities in myoglobinuria: review of the literature.
Reports of electrocardiographic abnormalities in association with myoglobinuria have been sparse and have included conduction disturbances, ST segment shifts, and T-wave changes. In many instances, these changes were noted in patients with underlying heart disease. We report a case of a 34-year-old woman with ST segment depression and T-wave inversion in the inferolateral leads during the acute episode of myoglobinuria. There was no demonstrable underlying heart disease, and there was parallel resolution of these ECG changes with myoglobinuria. We conclude that these ECG changes were produced by cardiac muscle involvement in a manner similar to that observed in skeletal muscle in myoglobinuria.
Adult↗
Influenza and myoglobinuria in brothers.
Two adult brothers became ill within 48 hours of each other, and both had severe myoglobinuria. One brother died of oliguric renal failure. The other did not have renal failure and survived. Acute influenza A infection was documented serologically and from throat washings in the surviving brother, and by isolation of the influenza A virus from throat cultures and lung tissue of the brother who died. 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. Neither brother had a history of recurrent episodes of myoglobinuria precipitated by exercise, cold, or fasting, thus making carnitine palmityl transferase deficiency unlikely.
Acute Kidney Injury↗
Myoglobinuria.
Myoglobinuria is still considered to be an uncommon occurrence, however, with the advent of better diagnostic tests it is being increasingly recognized as a potentially life-threatening complication of muscle necrosis. The pathologic consequences of myoglobinuria, including respiratory failure, hyperkalemia, and acute renal failure demand recognition by all who work in areas where this syndrome may develop. This article describes the role of myoglobin in the muscle and how myoglobinuria may develop. It includes the symptoms, differential diagnosis, and treatment of myoglobinuria and possible complications.
Humans↗
Myoglobinuria: evaluation of methods in the clinical diagnosis acute renal failure.
Patients with red--brown urine which may be a sign of myoglobinuria, can develop acute renal failure. We assayed serum creatinine, blood urea nitrogen (BUN) and creatine kinase activity in a total of 33 patients of equal groups, A (automobile accident), B (trauma) and C (undergoing rhabdomyolysis). In addition we tested 132 urine samples for the presence of myoglobin using a dipstick assay. Only five patients in group A showed any sign of myoglobinuria with increased creatine kinase activity upto 7 times the normal value but their serum creatinine level and BUN were within the normal range. In contrast, all 22 patients in group B and C showed myoglobinuria and above normal concentrations of serum creatinine and BUN, with significantly increased (p < 0.0001) creatine kinase activity upto 150 times the normal range. Four of the most seriously ill patients in group C developed acute renal failure. Supplementation of routine determinations of serum creatinine and BUN and serum creatine kinase activity with a rapid test for myoglobinuria provides an extra indication of impending renal dysfunction. It may be beneficial in the emergency management of these patients.
Acute Kidney Injury↗
Recurrent childhood myoglobinuria.
Recurrent heritable childhood myoglobinuria is a potentially fatal entity (mortality up to 35%) in which prompt diagnosis and treatment are critical. Sixty childhood cases have been reported between 1910 to 1988, most with undiagnosed etiologies. We have studied an additional 40 cases referred to CPMC (1980-1988), suggesting that this condition is largely underdiagnosed or unreported. We have found important differences between the childhood and adult-onset cases. Of 77 cases of adult-onset recurrent myoglobinuria, 45% have been diagnosed biochemically. In contrast, only 30% of the 60 childhood cases from the literature have been diagnosed; 11 with CPT deficiency and 7 with various glycolytic defects, and only 5 of our 40 childhood cases have been diagnosed, all with CPT deficiency. The 100 combined childhood cases can be divided into an exertional group (type I) with exertion as the leading precipitating factor (46 literature and 10 CPMC cases), a toxic group (type II) with infection and/or fever as the primary precipitant (14 literature and 23 CPMC cases), and 7 undefined cases. The type I group resembles the adult-onset group in which exercise is also the leading precipitating factor. There is a slight female predominance (male/female = 1:1.3) in the toxic group vs. a marked male predominance in the exertional and adult groups (4:1). Only 4 of 37 cases (11%) of the toxic group are diagnosed (all with CPT deficiency) vs. 19 of 56 cases (34%) of the exertional group (12 CPT, 7 glycolytic) and 45% of the adult group. The toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features, including ictal bulbar signs (8 of 18), encephalopathy (4 of 19), and seizures (2 of 7), as well as persistent cardiac abnormalities, developmental delay (4 of 17), and dysmorphic features (2 of 9). These clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies. A study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block.
Adolescent↗
Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria.
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.
Adolescent↗
Mitochondrial DNA deletions in inherited recurrent myoglobinuria.
We describe two brothers with inherited recurrent exertional myoglobinuria and alcohol intolerance associated with distinct morphological abnormalities of muscle mitochondria and multiple deletions of muscle mitochondrial DNA. Patient 1 (26 years old) and Patient 2 (21 years old) had recurrent episodes of myoglobinuria provoked by strenuous exercise or alcohol intake, from the age of 18 years. Although their serum lactate and pyruvate levels were normal at rest, they were significantly elevated by aerobic exercise. Histochemistry of their biopsied limb muscles showed ragged-red fibers and cytochrome c oxidase-negative fibers as well as degenerating and regenerating fibers. Electron microscopy showed pronounced accumulation of abnormal mitochondria containing paracrystalline inclusions and moderate increases of glycogen particles. The enzyme activities of the electron-transfer complexes in the isolated muscle mitochondria of Patient 2 were within normal ranges. Southern blot analysis revealed multiple deletions of mitochondrial DNA, some of which were common between the patients. Polymerase chain reaction of their muscle mitochondrial DNA detected multiple abnormal fragments indicating mitochondrial DNA deletions. We propose that a defect of the mitochondrial energy-transducing system due to multiple mitochondrial DNA deletions is a novel genetic cause of inherited recurrent myoglobinuria.
Adult↗
Recurrent myoglobinuria and HIV seropositivity: incidental or pathogenic association?
There have been few cases of polymyositis in patients with AIDS, and polymyositis is rarely a cause of myoglobinuria. We studied a 20-year-old homosexual man with recurrent myoglobinuria. He was asymptomatic between episodes. Each episode was accompanied by muscle pain, limb weakness, high serum levels of creatine kinase, and pigmenturia. Muscle biopsy showed active necrosis without inflammation or abnormalities of glycolytic or other energy-generating enzymes. Antibodies to HIV were present in serum. Clinical evidence of AIDS has not developed in 2 years. Recurrent myoglobinuria may be another consequence of HIV infection.
Adult↗