title: Prevalence and distribution of the c.1436C→T sequence variant of carnitine palmitoyltransferase 1A among Alaska Native infants.
abstract: OBJECTIVE
  To use genotype analysis to determine the prevalence of the c.1436C→T sequence variant in carnitine palmitoyltransferase 1A (CPT1A) among Alaskan infants, and evaluate the sensitivity of newborn screening by tandem mass spectrometry (MS/MS) to identify homozygous infants.
  
  
  METHODS
  We compared MS/MS and DNA analyses of 2409 newborn blood spots collected over 3 consecutive months.
  
  
  RESULTS
  Of 2409 infants, 166 (6.9%) were homozygous for the variant, all but one of whom were of Alaska Native race. None of the homozygous infants was identified by MS/MS on the first newborn screen using a C0/C16 + C18 cutoff of 130. Among 633 Alaska Native infants, 165 (26.1%) were homozygous and 218 (34.4%) were heterozygous for the variant. The prevalence was highest in Alaska's northern/western regions (51.2% of 255 infants homozygous; allele frequency, 0.7).
  
  
  CONCLUSIONS
  The CPT1A c.1436C→T variant is prevalent among some Alaska Native peoples, but newborn screening using current MS/MS cutoffs is not an effective means to identify homozygous infants. The clinical consequences of the partial CPT1A deficiency associated with this variant are unknown. If effects are substantial, revision of newborn screening, including Alaska-specific MS/MS cutoffs and confirmatory genotyping, may be needed.
authors.affiliation: Alaska Division of Public Health, Anchorage, AK, USA. Brad.Gessner@alaska.gov
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Gessner
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Gillingham
authors.forename: Monique A
authors.initials: MA
authors.lastname: Johnson
authors.forename: C Sue
authors.initials: CS
authors.lastname: Richards
authors.forename: William E
authors.initials: WE
authors.lastname: Lambert
authors.forename: David
authors.initials: D
authors.lastname: Sesser
authors.forename: Leanne C
authors.initials: LC
authors.lastname: Rien
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hermerath
authors.forename: Michael R
authors.initials: MR
authors.lastname: Skeels
authors.forename: Stephanie
authors.initials: S
authors.lastname: Birch
authors.forename: Cary O
authors.initials: CO
authors.lastname: Harding
authors.forename: Thalia
authors.initials: T
authors.lastname: Wood
authors.forename: David M
authors.initials: DM
authors.lastname: Koeller
mesh_terms: D000413:Alaska; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007198:Indians, North American; D007231:Infant, Newborn; D015997:Neonatal Screening; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D002334:Carnitine O-Palmitoyltransferase