CPT1A Arctic Variant

Carntitine Palmitoyl Transferase, Type 1A Arctic Variant (CPT1A Acrtic Variant)
(Adapted from Pocket Guide to Alaska Native Pediatric Diagnoses)
Pathophysiology: Fatty acid oxidation disorder: difficulty breaking down fatty acids from both food and body fat.
Inheritance: Autosomal recessive
Demographics:

Considered to be the wild-type (normal) gene in the Yu'pik population in Alaska (50% are homozygous for the Arctic Variant)
Total incidence per year in newborns in Alaska =7%
Found at a higher rate in all circumpolar coastline populations including Inuit populations in Canada and Greenland and indigenous populations of northern Siberia
General population = <1/1,000,000 (general CPT1A deficiency)

Signs/Symptoms:

Most children never have symptoms, but if they do, symptoms are more likely to be seen in children <2 years old
Initial signs of metabolic crisis: sleepiness, irritability, poor appetite
Metabolic crisis: Hypoglycemia (hypoketotic), seizures due to hypoglycemia, Death (especially associated with a concomitant infectious disease, although rare)

Diagnosis: Alaska Newborn Screen (processed in Oregon) - added to screen in the fall of 2003.
Management:

Avoid fasting states
When healthy, children with CPT1A Arctic Variant should eat like any other child their age
When sick, if infants and toddlers are unable to tolerate glucose-containing fluids (Pedialyte, juice, sports drinks) or food for more than 6 to 8 hours, they should see a health care provider immediately to consider IV or NG glucose-containing fluids.
Children with CPT1A Arctic Variant who are NPO on IV fluids should always be on dextrose containing fluids (D5-NS or D5-1/2NS). A normal maintenance rate is all that is needed.

Critical Times for Affected Patients:

Fasting or illness during first 2 years of life
fever, moderate/severe infection, dehydration, Surgery

Resources:

The Arctic Variant of CPT-1A (Powerpoint Presentation by Matthew Hirschfeld,MD/PhD)
Newborn Screening Information for Parents: https://www.newbornscreening.info/Parents/fattyaciddisorders/CPT1AV.html
YouTube: "The Other Energy Crisis: Arctic Variant CPT1A" https://www.youtube.com/watch?v=g-JRZ7PO3yk
CPT1 Deficiency brochure
Gillingham et al. Impaired fasting tolerance among Alaska Native Children with a common Carnitine Palmitoyltransferase 1A sequence variant. Molecular Genetics and Metabolism. 2011. doi: 10.1016/j.ymgme.2011.06.017.