MULTIPLE RESPIRATORY-CHAIN ABNORMALITIES ASSOCIATED WITH HYPERTROPHICCARDIOMYOPATHY AND 3-METHYLGLUTACONIC ACIDURIA

In a 4.5-month-old boy presenting with marked muscular hypotonia in th e neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypogl ycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methy lglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydr oxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of choleste rol biosynthesis in cultured fibroblasts and in different tissues post mortem revealed no enzyme deficiency. Analyses of the respiratory chai n in postmortem tissues demonstrated severe impairment of complex I (N ADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) a ctivities in skeletal muscle and reduced complex IV activity in heart.