title: Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency.
abstract: Liver carnitine palmitoyltransferase I (CPT I) deficiency is a rare disorder of hepatic mitochondrial long-chain fatty acid oxidation. It characteristically presents with symptoms associated with failure of ketogenesis (hypoketotic hypoglycemia). The disorder is due to mutations in the CPT 1A gene for which few patients have been characterized. We present here four novel mutations in five patients from four families with severe enzyme deficiency. Three of these are missense mutations (G465W, R316G, and F343V) and the fourth a nonsense mutation (R160X). Other than small Inuit and Hutterite populations in Canada and the Northern plains, there is complete heterogeneity of disease-causing mutations within CPT I deficient families with each demonstrating unique mutations. Because there are no easily recognizable disease-specific metabolite markers, diagnostic confirmation of this disorder requires a combination of enzymatic analysis and whole gene sequencing.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9072, USA. michaelj.bennett@email.swmed.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bennett
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boriack
authors.forename: Srinivas
authors.initials: S
authors.lastname: Narayan
authors.forename: S Lane
authors.initials: SL
authors.lastname: Rutledge
authors.forename: Michael L
authors.initials: ML
authors.lastname: Raff
mesh_terms: D000293:Adolescent; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics; D007223:Infant; D007659:Ketones / Q000378:metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D007659:Ketones; D002334:Carnitine O-Palmitoyltransferase