Fasting medium chain acyl-coenzyme A dehydrogenase--deficient children can make ketones.
Medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency classically presents as hypoketotic hypoglycemia. Under-production of ketones has been presumed to be the cause of hypoketosis, but this has never been proven. Stable isotope dilution studies of ketone kinetics were performed on three well children with homozygous 985G MCAD deficiency using 1,3-13C2 sodium acetoacetate and 1,2,3,4-13C4 sodium 3-hydroxybutyrate to ascertain the rates of ketone production, interconversion, and use. All children were fasted for 9 to 11.5 hours before the beginning of the study period. Euglycemia was maintained in all cases. Ketone kinetics were calculated using a two-accessible pool model and showed normal ketone production in all three children compared with published control data from children fasted for a similar length of time. There is no evidence for underproduction or overuse of ketones 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 production and result in the biochemical phenotype recognized in unwell children.
Fletcher
J M
JM
Murdoch Institute and Department of Clinical Biochemistry, Royal Children's Hospital, Parkville, Victoria, Australia.
Pitt
J J
JJ
D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000090:Acetoacetates / Q000097:blood / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase; D017668:Age of Onset; D002247:Carbon Isotopes; D002648:Child; D002675:Child, Preschool; D005215:Fasting / Q000502:physiology*; D044943:Fatty Acid Desaturases / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D007223:Infant; D007657:Ketone Bodies / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological
D000090:Acetoacetates; D002247:Carbon Isotopes; D007657:Ketone Bodies; C016635:acetoacetic acid; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D020155:3-Hydroxybutyric Acid