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

Melanie B Gillingham1, Matthew Hirschfeld, Sarah Lowe

  • 1Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA. gillingm@ohsu.edu

Molecular Genetics and Metabolism
|July 19, 2011
PubMed

Insights

A CPT1A gene variant common in Alaska Native newborns impairs the body's ability to produce ketones during fasting, potentially causing hypoketotic hypoglycemia in children.

Area of Science:

  • Biochemistry
  • Genetics
  • Pediatrics

Background:

  • A specific CPT1A gene variant (c.1436C→T) is prevalent in Alaska Native newborns.
  • The clinical significance of this CPT1A variant has not been previously understood.

Purpose of the Study:

  • To investigate the metabolic consequences of homozygosity for the c.1436C→T CPT1A variant in children.
  • To determine the impact of this variant on fasting metabolism and ketogenesis.

Main Methods:

  • Medically supervised fasting was performed in five children homozygous for the c.1436C→T variant.
  • Plasma free fatty acids, long-chain acylcarnitines, and ketone production were monitored during fasting.

Main Results:

  • Children homozygous for the variant showed normal increases in plasma free fatty acids.
  • Long-chain acylcarnitine levels and ketone production were significantly blunted in these children.
  • Two children experienced early termination of fasting due to hypoglycemia symptoms.

Conclusions:

  • Homozygosity for the c.1436C→T CPT1A variant significantly impairs fasting ketogenesis.
  • This genetic variant can lead to hypoketotic hypoglycemia in young children, particularly those of Alaska Native descent.

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