Fatal cardiomyopathy associated with 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase; EC 4.1.3.4; McKusick 246450) is an inborn error of ketogenesis and L-leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy and apnoea. Biochemically there is a characteristic absence of ketonuria with hypoglycaemia, acidosis and variable hyperammonaemia (Gibson et al 1988). The urinary organic acid profile includes elevated concentrations of 3-hydroxyisovaleric (3-HI[V), cis- and trans-3-methylglutaconic (3-MGC), 3-methylglutaric (3-MGR), and 3-hydroxy-3-methylglutaric (HMG) acids. Confirmatory enzyme diagnosis is made in cultured fibroblasts or leukocytes. In this report we describe a patient with HMG-CoA lyase deficiency who manifested a fatal arrhythmia associated with dilated cardiomyopathy, a clinical feature previously unreported in HMG-CoA lyase deficiency.