Medium-chain acyl-CoA dehydrogenase deficiency: metabolic effects and therapeutic efficacy of long-term L-carnitine supplementation.
Medium-chain acyl-CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium-chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium-chain acyl-CoA dehydrogenase deficiency. We report the results of carefully monitored fasting challenges of an infant with this deficiency both before and after 3 months of oral carnitine therapy. Carnitine supplementation failed to prevent lethargy, vomiting, hypoglycaemia and accumulation of free fatty acids in response to fasting despite normalization of plasma carnitine levels and a marked increase in urinary excretion of acyl-carnitine esters. Potentially toxic medium-chain fatty acids accumulated in the plasma in spite of therapy. Based on this study of one patient, we stress that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy for medium-chain acyl-CoA dehydrogenase deficient patients.
Treem
W R
WR
Division of Pediatric Gastroenterology and Nutrition, Hartford Hospital, University of Connecticut School of Medicine, Hartford 06115.
Stanley
C A
CA
Goodman
S I
SI
D020155:3-Hydroxybutyric Acid; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D002331:Carnitine / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D002849:Chromatography, Gas; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007223:Infant; D008052:Lipid Metabolism, Inborn Errors / Q000178:diet therapy* / Q000201:enzymology / Q000378:metabolism; D008297:Male
D005227:Fatty Acids; D006885:Hydroxybutyrates; D044944:Acyl-CoA Dehydrogenases; D002331:Carnitine; D020155:3-Hydroxybutyric Acid