Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria.

A 14-year-old boy had myoglobinuria and renal failure after intense exercise; a year earlier he had experienced a milder episode. There was no consanguinity and no family history of neuromuscular diseases or hemolytic anemia. Strength was normal. Forearm ischemic exercise caused prolonged contracture with no rise of venous lactate. Muscle morphology showed only a mild increase of lipid droplets. Glycogen concentration was normal. Muscle phosphoglycerate kinase (PGK) activity was 5% of the normal mean, and all other glycolytic enzymes were normal. The residual PGK activity of muscle was heat stable but showed slower than normal electrophoretic mobility and decreased Michaelis constants for 3-phosphoglycerate and adenosine triphosphate. The enzyme defect was also expressed in erythrocytes and in fibroblast and muscle cultures. PGK activity was decreased in tissues from the patient's mother but normal in the father. PGK deficiency is an X-linked recessive trait usually associated with hemolytic anemia, mental retardation, and seizures; myopathy had not been recognized previously. 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.