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"

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1. Metabolic Response to Fasting in children with CPT1A deficiency

(A) Change in C16:0 acylcarnitine (B) C18:0 acylcarnitine in 5 subjects homozygous for the c.1436C>T variant of CPT1A are compared to published data for children free of a FAO disorder. Normal control data is presented as the mean (•---•---•) and the range (grey shading) at 0, 15, and 20 hours of fasting [12]. (C) Change in free fatty acids (FFA) (D) ketones (E) the FFA:ketone ratio and (F) glucose in each of 5 subjects who are homozygous for the c.1436C>T variant of CPT1A are compared to published normal data. Normal control data is presented as the mean (•---•---•) and the 10th and 90th percentiles (grey shading) at 15, 18 and 24 hours of fasting [11].