IDENTIFICATION OF 4 NOVEL MUTATIONS IN PATIENTS WITH CARNITINE PALMITOYLTRANSFERASE-II (CPT II) DEFICIENCY

Carnitine palmitoyltransferase II (CPT II) deficiency, an autosomal re cessive disorder of fatty-acid oxidation, presents as three distinct p henotypes (neonatal, infantile, and adult onset). In order to investig ate the molecular basis of these three phenotypes, six patients with C PT II deficiency have been studied. All six unrelated patients in this study experienced the clinical symptoms of CPT II deficiency. Three p atients had the neonatal form, one had the milder infantile form, and the remaining two had the adult-onset form with ''muscular'' symptoms only. Their diagnoses were based upon in vitro analysis of the mitocho ndrial beta-oxidation pathway in fibroblasts and standard enzyme assay s. We devised a method to screen the entire coding sequence and flanki ng splice junction of the CPT II gene. A total of six different mutati ons have been identified, including four novel mutations. Among them, the previously reported common mutation, S113L, was only found in 3 of 12 variant alleles. Three of the six mutations have been identified i n a few unrelated patients, while the remaining three have been found in single families. This study, as well as those by others, indicates genetic heterogeneity in this disease. In addition to tabulating the m utations, the correlation of mutant genotype to clinical phenotype is briefly discussed. (C) 1998 Academic Press.