Three children from unrelated families presented in early childhood with
hypoglycemia and cardiorespiratory arrests associated with fasting. Significant
hepatomegaly,
cardiomegaly, and
hypotonia were present at the time of initial presentation.
Ketones were not present in the urine at the time of
hypoglycemia in any patient; however, dicarboxylic aciduria was documented in one patient at the time of the acute episode and in two patients during fasting studies. Total plasma
carnitine concentration was low with an increased esterified
carnitine fraction. These findings suggested a defect in mitochondrial
fatty acid oxidation, and specific assays were performed for the
acyl coenzyme A (
CoA)
dehydrogenases. These analyses showed that the activity of the
long-chain acyl CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver tissue. Activities of the medium-chain, short-chain, and
isovaleryl CoA dehydrogenases were not different from control values. With cultured fibroblasts, CO2 evolution from long-chain
fatty acids was significantly reduced, while CO2 evolution from medium-chain and
short-chain fatty acids was comparable to control values--findings consistent with a defect early in the beta-oxidation sequence. Studies of
acyl CoA dehydrogenase activities in fibroblasts and leukocytes from parents of the patients showed levels of
long-chain acyl CoA dehydrogenase activity intermediate between affected and control values and indicated an autosomal recessive form of inheritance of this enzymatic defect.(ABSTRACT TRUNCATED AT 250 WORDS)