title: Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient.
abstract: Carnitine palmitoyl transferase II deficiency, an inherited disorder of long-chain fatty acid oxidation, may result in either a mild form (muscle disease in adults) or a severe form (hepatocardiomuscular syndrome in infants). The difference in severity between these two forms is related to a difference in levels of residual carnitine palmitoyl transferase II activity and long-chain fatty acid oxidation and in genotypes. Few data are, however, available regarding compound heterozygotes for a 'mild' and a 'severe' carnitine palmitoyl transferase II mutation. We report on such a patient carrying both the 'mild' S113L substitution and the 'severe' Y628S mutation. The patient's clinical picture (cardiac arrest at 6 years) was markedly more serious than usually observed in S113L homozygotes, and suggested that 'mild'/'severe' compound heterozygosity makes patients at risk from life-threatening events. Palmitate oxidation and carnitine palmitoyl transferase II activity were lower in lymphocytes from the S113L/Y628S patient than in those from a S113L homozygote. Thus, assessment of carnitine palmitoyl transferase II mutations, long-chain fatty acid oxidation, and carnitine palmitoyl transferase II activity, may help in predicting the potential severity of the muscular form of carnitine palmitoyl transferase II deficiency.
authors.affiliation: Laboratoire de Biochimie Génétique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, F-75743, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Thuillier
authors.forename: C
authors.initials: C
authors.lastname: Sevin
authors.forename: F
authors.initials: F
authors.lastname: Demaugre
authors.forename: M
authors.initials: M
authors.lastname: Brivet
authors.forename: D
authors.initials: D
authors.lastname: Rabier
authors.forename: V
authors.initials: V
authors.lastname: Droin
authors.forename: J
authors.initials: J
authors.lastname: Aupetit
authors.forename: N
authors.initials: N
authors.lastname: Abadi
authors.forename: P
authors.initials: P
authors.lastname: Kamoun
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: J P
authors.initials: JP
authors.lastname: Bonnefont
mesh_terms: D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D017240:Mitochondrial Myopathies / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D002334:Carnitine O-Palmitoyltransferase