3-Methylcrotonyl-CoA carboxylase deficiency in an infant with cardiomyopathy, in her brother with developmental delay and in their asymptomatic father (original) (raw)
Three aected members of one family, each with a dierent clinical presentation of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase (MCC) de®ciency are described. The index patient presented at 7 weeks of age with feeding diculties, sweating and tachypnoea. Echocardiography showed a severely dilated left ventricle with minimal contractility. MCC de®ciency was suspected on the basis of elevated urinary excretion of 3-hydroxyisovalerate and 3-methylcrotonylglycine. De®ciency of MCC activity was found in lymphocytes and ®broblasts (ca. 2% of mean normal). Serum carnitine was low (free 10 lmol/l). Some other possible causes of cardiomyopathy were excluded. Cardiomyopathy was not improved by carnitine therapy. The healthy father and a developmentally delayed brother also had MCC de®ciency. Both also had decreased serum carnitine concentrations, but without cardiac involvement. Dilatative cardiomyopathy as predominant symptom in isolated MCC de®ciency has not been described before, although severe carnitine de®ciency is a common ®nding in MCC de®ciency. It is not clear whether this is a coincidental association. Conclusion In order to understand the phenotypic spectrum of this rare disorder, cardiac evaluation should be made in patients with 3-methylcrotonyl-CoA carboxylase de®ciency. Biochemical and clinical investigations have also to be performed in their parents and siblings. In addition, 3-methylcrotonyl-CoA carboxylase de®ciency should be included in the dierential diagnosis of dilatative cardiomyopathy.