Fasting medium chain acyl-coenzyme A dehydrogenase-deficient children can make ketones

Medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency classically pr esents as hypoketotic hypoglycemia. Underproduction of ketones has been pre sumed to be the cause of hypoketosis, but this has never been proven. Stabl e isotope dilution studies of ketone kinetics were performed on three well children with homozygous 985G MCAD deficiency using 1,3-C-13(2) sodium acet oacetate end 1,2,3,4-C-13(4) sodium a-hydroxybutyrate to ascertain the rate s of ketone production, interconversion, and use. All children were fasted for 9 to 11.5 hours before the beginning of the study period. Euglycemia wa s maintained in all cases. Ketone kinetics were calculated using a two-acce ssible pool model and showed normal ketone production in all three children compared with published control data from children fasted for a similar le ngth of time. There is no evidence for underproduction or overuse of ketone s in these MCAD-deficient children, at least when they are well. We propose that another factor, such as fever, may be required to reduce ketone produ ction and result in the biochemical phenotype recognized in unwell children . Copyright (C) 2001 by W.B. Saunders Company.