Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): evidence for a founder effect and results of a pilot study on a DNA-based newborn screening program

Mol Genet Metab. 2001 May;73(1):55-63. doi: 10.1006/mgme.2001.3149.

Abstract

We describe six patients with hepatic carnitine palmitoyl transferase (CPT1 A) deficiency who are members of a large extended Hutterite kindred living in widely scattered communities in the United States and Canadian Prairies. Two patients have significant neurological impairment due to severe recurrent hypoglycemic crises. The remaining four patients with earlier detection and treatment have near normal outcomes. The Canadian and American Hutterite families share two common ancestors who married in 1812, about 60 years before the Hutterites arrived in North America and prior to their subdivision into the three groups (Schmiedeleut, Dariusleut, and the Lehrerleut). These patients share a common haplotype on chromosome 11q13 and are all homozygous for a common CPT1 A G710E mutation, suggesting a founder effect. The clustering of such a rare disorder of fatty acid oxidation prompted us to initiate a pilot DNA-based neonatal screening program to determine the carrier frequency of this mutation in Hutterite newborns with the participation and support of the community. To date our carrier frequency is 1/16, close to the predicted frequency based on diagnosed patients and number of births. We believe our newborn screening program for CPT1 A deficiency in the Hutterite community will serve as a prototype model for delivery of targeted genetic services to other similar unique genetic isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Carnitine O-Palmitoyltransferase / deficiency
  • Carnitine O-Palmitoyltransferase / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 11 / genetics
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Ethnic Groups / genetics*
  • Family Health
  • Female
  • Founder Effect
  • Genetic Linkage
  • Haplotypes
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / diagnosis
  • Infant, Newborn, Diseases / enzymology
  • Infant, Newborn, Diseases / genetics
  • Liver / enzymology*
  • Male
  • Manitoba
  • Microsatellite Repeats
  • Mutation
  • Neonatal Screening / methods
  • North America
  • Pedigree
  • Pilot Projects

Substances

  • DNA
  • Carnitine O-Palmitoyltransferase