Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria

Abstract 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/1, 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.