title: Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency.
abstract: Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full clinical spectrum of disease. Severe and intermediate phenotypes show a clear correlation with biochemical indices and genetic analysis revealed causative mutations in most patients. Studies of mild phenotypes suggest a more complex interaction, with higher residual fatty acid oxidation, a wider range of CPT II activity (10-60%) but little evidence of genotype-phenotype correlation. Residual CPT II mutant protein from myopathic patients shows thermal instability at 41 degrees C. The common 'polymorphisms' V3681 and M647V are strikingly overrepresented in the myopathic patients, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88% of patients, suggesting increased susceptibility to clinical disease. A small number of symptomatic patients appear to have significant residual CPT II activity (42-60%) The synergistic interaction of partial deficiencies of CPT II, muscle adenosine monophosphate deaminase and possibly other enzymes of muscle energy metabolism in the aetiology of episodic myopathy deserves wider consideration.
authors: Department of Clinical Chemistry, Sheffield Children's Hospital, UK.
authors: S E
authors: SE
authors: Olpin
authors: A
authors: A
authors: Afifi
authors: S
authors: S
authors: Clark
authors: N J
authors: NJ
authors: Manning
authors: J R
authors: JR
authors: Bonham
authors: A
authors: A
authors: Dalton
authors: J V
authors: JV
authors: Leonard
authors: J M
authors: JM
authors: Land
authors: B S
authors: BS
authors: Andresen
authors: A A
authors: AA
authors: Morris
authors: F
authors: F
authors: Muntoni
authors: D
authors: D
authors: Turnbull
authors: M
authors: M
authors: Pourfarzam
authors: S
authors: S
authors: Rahman
authors: R J
authors: RJ
authors: Pollitt
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D013696:Temperature
chemical_list: D010168:Palmitates; D002334:Carnitine O-Palmitoyltransferase; D000659:AMP Deaminase