Secondary respiratory chain defect in a boy with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: possible diagnostic pitfalls

We report on a boy who suffered from microcephaly, growth retardation, card iomyopathy and hepatic dysfunction. When he had his first febrile infection at the age of 3 months he showed metabolic decompensation. Laboratory para meters and clinical features were compatible with a beta-oxidation defect o r a respiratory chain disorder. Measurement of beta-oxidation enzymes showe d long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency; determinat ion of respiratory chain complex activities revealed complete absence of co mplex I, II, III and IV activities in skeletal muscle and reduced activitie s of complexes II and IV in cultured fibroblasts, with secondary dysregulat ion of ATP synthase. The patient was found to be homozygous for the MTP:G15 28 C mutation (LCHAD-deficiency). Conclusion This patient had LCHAD deficiency as his primary metabolic disor der, leading to secondary inhibition of respiratory chain enzymes by 'toxic ' metabolites.