Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant

Mol Genet Metab. 2011 Nov;104(3):261-4. doi: 10.1016/j.ymgme.2011.06.017. Epub 2011 Jun 28.

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"

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alaska
  • American Native Continental Ancestry Group
  • Body Mass Index
  • Carnitine / analogs & derivatives
  • Carnitine / biosynthesis
  • Carnitine O-Palmitoyltransferase / deficiency
  • Carnitine O-Palmitoyltransferase / genetics*
  • Child, Preschool
  • Fatty Acids, Nonesterified / blood
  • Gas Chromatography-Mass Spectrometry
  • Homozygote
  • Humans
  • Hypoglycemia / complications
  • Hypoglycemia / etiology*
  • Hypoglycemia / genetics
  • Ketones / metabolism
  • Lipid Metabolism, Inborn Errors / complications*
  • Lipid Metabolism, Inborn Errors / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Tandem Mass Spectrometry

Substances

  • Fatty Acids, Nonesterified
  • Ketones
  • acylcarnitine
  • Carnitine O-Palmitoyltransferase
  • Carnitine

Supplementary concepts

  • Carnitine palmitoyl transferase 1A deficiency

Associated data

  • ClinicalTrials.gov/NCT00653666