title: Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant.
abstract: A high prevalence of the sequence variant c.1436C→T in the CPT1A gene has been identified among Alaska Native newborns but the clinical implications of this variant are unknown. We conducted medically supervised fasts in 5 children homozygous for the c.1436C→T variant. Plasma free fatty acids increased normally in these children but their long-chain acylcarnitine and ketone production was significantly blunted. The fast was terminated early in two subjects due to symptoms of hypoglycemia. Homozygosity for the c.1436C→T sequence variant of CPT1A impairs fasting ketogenesis, and can cause hypoketotic hypoglycemia in young children. Trial registration www.clinical trials.gov NCT00653666 "Metabolic Consequences of CPT1A Deficiency"
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA. gillingm@ohsu.edu
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Gillingham
authors.forename: Matthew
authors.initials: M
authors.lastname: Hirschfeld
authors.forename: Sarah
authors.initials: S
authors.lastname: Lowe
authors.forename: Dietrich
authors.initials: D
authors.lastname: Matern
authors.forename: James
authors.initials: J
authors.lastname: Shoemaker
authors.forename: William E
authors.initials: WE
authors.lastname: Lambert
authors.forename: David M
authors.initials: DM
authors.lastname: Koeller
mesh_terms: D000413:Alaska; D044467:American Indian or Alaska Native; D015992:Body Mass Index; D002331:Carnitine / Q000031:analogs & derivatives / Q000096:biosynthesis; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics*; D002675:Child, Preschool; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006720:Homozygote; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000209:etiology* / Q000235:genetics; D007659:Ketones / Q000378:metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D005230:Fatty Acids, Nonesterified; D007659:Ketones; C116917:acylcarnitine; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine