VITAMIN-RESPONSIVE COMPLEX-I DEFICIENCY IN A MYOPATHIC PATIENT WITH INCREASED ACTIVITY OF THE TERMINAL RESPIRATORY-CHAIN AND LACTIC-ACIDOSIS

An 11-year-old girl with exercise intolerance, fatiguability from earl y childhood, had high blood lactate levels. Histochemistry showed incr eased activity of succinate dehydrogenase at the periphery of the musc le fibres, whereas aggregates of mitochondria were seen by electron mi croscopy. Biochemical investigation of isolated mitochondria and homog enate from muscle showed evidence of a severe complex I deficiency. In contrast, succinate dehydrogenase, complex II+III and complex IV were increased in activity. Therapy with biotin, riboflavin, nicotinamide, carnitine and amino acids resulted in an improvement of her endurance . P-31 NMR spectroscopy Of her forearm muscle showed a decreased ratio of phosphocreatine (PCr) over ATP. After exercise the PCr recovery ra te was 26% of the average rate in 20 healthy untrained controls. When the therapy was suspended the PCr/ATP ratio at rest decreased from 2.6 0 to 2.34, and the PCr recovery rate after exercise decreased to 21% o f the average control rate. The therapy was reinstituted but only ribo flavin and carnitine were given. The PCr/ATP ratio increased to 2.60 a nd the PCr recovery rate increased to 32% of the control rate. Improve ment of the energy metabolism in patients with defects in the oxidativ e phosphorylation may add to the quality of life; P-31 NMR spectroscop y can measure these improvements.