3-Methylcrotonyl-CoA carboxylase deficiency in an infant with cardiomyopathy, in her brother with developmental delay and in their asymptomatic father

Three affected members of one family, each with a different clinical presen tation of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency are described. The index patient presented at 7 weeks of age wit h feeding difficulties, sweating and tachypnoea. Echocardiography showed a severely dilated left ventricle with minimal contractility. MCC deficiency was suspected on the basis of elevated urinary excretion of 3-hydroxyisoval erate and 3-methylcrotonylglycine. Deficiency of MCC activity was found in lymphocytes and fibroblasts (ca. 2% of mean normal). Serum carnitine was lo w (free 10 mu mol/l). Some other possible causes of cardiomyopathy were exc luded. Cardiomyopathy was not improved by carnitine therapy. The healthy fa ther and a developmentally delayed brother also had MCC deficiency. Both al so had decreased serum carnitine concentrations, but without cardiac involv ement. Dilatative cardiomyopathy as predominant symptom in isolated MCC def iciency has not been described before, although severe carnitine deficiency is a common finding in MCC deficiency. It is not clear whether this is a c oincidental association. Conclusion Tn order to understand the phenotypic spectrum of this rare diso rder, cardiac evaluation should be made in patients with 3-methylcrotonyl-C oA carboxylase deficiency. Biochemical and clinical investigations have als o to be performed in their parents and siblings. In addition, 3-methylcroto nyl-CoA carboxylase deficiency should be included in the differential diagn osis of dilatative cardiomyopathy.