Short-chain 3-hydroxyacylCoA dehydrogenase (SCHAD) deficiency

Deficiency of hydroxyacylCoA dehydrogenase (HADH) was first described by Tein and colleagues in a 16-year-old girl with recurrent myoglobinuria and hypoketotic hypoglycemia in whom HADH activity was markedly diminished in muscle, but normal in fibroblasts. The initial patient with deficiency of HADH had episodic myoglobinuria and hypoketotic hypoglycemia, as expected for a disorder of fatty acid oxidation. There was also evidence of encephalopathy and hypertrophic dilated cardiomyopathy. The disorder is transmitted in an autosomal recessive fashion. Consanguinity has been observed and heterozygosity has been demonstrated by enzyme assay of the liver and by mutational analysis. Treatment with carnitine and a diet low in fat appears to be prudent. Treatment with glucagon and diazoxide has been employed in the severe hyperinsulinemic hypoglycemic patients. SCHAD deficiency appears to cause hyperinsulinemia by activation of glutamic dehydrogenase (GDH) via loss of the normal inhibitory regulation of GDH by SCHAD.