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The case of an adolescent with idiopathic recurrent myoglobinuria is reported. The following features are emphasized: (1) persistence of limb weakness and elevated CK levels between the attacks, (2) a constant myopathic pattern in EMG, and (3) chronic morphologic abnormalities of myopathy in two muscle biopsies. All known causes of myoglobinuria were investigated and ruled out.

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.

Muscle phosphoglycerate mutase (PGAM) activity was markedly decreased (6% of the normal mean) in a 17-year-old girl with recurrent myoglobinuria after intense exercise. Muscle biopsy showed increased PAS stain; glycogen concentration was twice normal. Studies of anaerobic glycolysis in vitro showed decreased lactate production with glycogen, and with all hexose phosphate glycolytic intermediates, which was corrected by addition of purified PGAM to the reaction mixtures. A defect of the M subunit of PGAM was documented by electrophoretic, heat lability, and mercury inhibition studies. Intermediate PGAM activities (39 and 50% of normal) were found in muscle biopsies from the patient's asymptomatic parents. These data confirm the clinical, morphologic, and biochemical features described in the first patient with PGAM deficiency and suggest autosomal-recessive transmission of the trait.

A 52-year-old man complained since adolescence of cramps and pigmenturia after 15 to 30 minutes of intense exercise. There was no family history of neuromuscular diseases, and strength was normal. The rise of venous lactate after forearm ischemic exercise was abnormally low. Histochemical and ultrastructural studies of a muscle biopsy showed mild increase of glycogen, which was confirmed by biochemical analysis. Studies of anaerobic glycolysis in vitro showed decrease lactate formation with glycogen and with all hexosephosphate glycolytic intermediates, suggesting a defect below the phosphofructokinase reaction. Muscle phosphoglycerate mutase (PGAM) activity was 5.7% of the lowest control, while all other enzymes of glycolysis had normal activities. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity of PGAM in the patient's muscle was represented by the brain (BB) isoenzyme, suggesting a genetic defect of the M subunit that predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.