Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient

Carnitine palmitoyl transferase II deficiency, an inherited disorder of lon g-chain fatty acid oxidation, may result in either a mild form (muscle dise ase in adults) or a severe form (hepatocardiomuscular syndrome in infants). The: difference in severity between these two Terms is related to a differ ence in levels of residual carnitine palmitoyl transferase II activity and long-chain fatty acid oxidation and in genotypes. Few data are. however. av ailable regarding compound heterozygotes for a 'mild' and a 'severe' carnit ine palmitoyl transferase II mutation. We report on such a patient carrying both the 'mild' S113L substitution and the 'severe' Y628S mutation. The pa tient's clinical picture (cardiac arrest at 6 years) was markedly more seri ous than usually observed in S113L homozygotes. and suggested that 'mild'/' severe' compound heterozygosity makes patients at risk from life-threatenin g events. Palmitate oxidation and carnitine palmitoyl transferase II activi ty were lower in lymphocytes from the S113L/Y628S patient than in those fro m a S113L homozygote. Thus, assessment of carnitine palmitoyl transferase I I mutations, long-chain fatty acid oxidation, and carnitine palmitoyl trans ferase II activity, may help in predicting the potential severity of the mu scular form of carnitine palmitoyl transferase II deficiency. (C) 2000 Else vier Science B.V. All rights reserved.