Molecular Genetics Carnitine Palmitoyltransferase 1A (CPT1A) Deficiency

Deficiency of the hepatic form of carnitine palmitoyltransferase I (CPT1A) is a rare disorder of fatty acid oxidation, usually presenting with hypoketotic hypoglycemia often associated with fasting or viral illness.  The disorder is caused by mutations in the CPT1A gene, found on chromosome 11q13.1 and is autosomal recessive.  CPT1A deficiency is estimated to have an incidence of 1 in 960 in the Alaska Native population.  CPT1A deficiency in this population has been shown to be caused primarily by a mutation of 1436C>T (P479L) in the CPT1A gene.

Reasons for Referral:

• Confirmation of clinical diagnosis in Alaska Native patients identified with CPT1A deficiency.
• Carrier testing for Alaska Native family members of an affected individual.
• Prenatal diagnosis for Alaska natives when both reproductive partners have the c.1436C>T mutation.

Testing for the CPT1A 1436C>T mutation is carried out by allelic discrimination using TaqMan probes on the ABI 7500 Fast Real-Time PCR platform.  This methodology uses a primer pair that flanks the nucleotide position of interest and two probes, each labeled with a different fluorescent dye, that anneal to the two different alleles.  If the probe hybridizes to the DNA, when the primer is extended during PCR, the probe is displaced by the Taq enzyme and fluorescence results.  The fluorescence is measured at the end of the PCR amplification in a single read to determine the sample genotype.

Test reporting follows the American College of Medical Genetics (ACMG) guidelines.

Blood: Draw purple (EDTA) or yellow top (ACD) tube:

• Adult: 4mL
• Child: 4mL
• Infant: 2-3mL

Blood Spot:  Collected on newborn screen collection card.
Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)
Prenatal:

• Direct Amniotic Fluid (10-20mL)
• Direct CVS
• Cultured Amnio or CVS (2-T25 flasks)

DNA: 10ng at a minimum of 50ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

• Maternal cell rule-out testing will be performed on all prenatal specimens received.Please provide maternal blood in addition to the fetal specimen.Additional charges apply for the maternal cell rule-out test.
• All genetic testing performed on Direct CVS or Direct Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories.Cell cultures will be prepared from the specimen received.Additional charges apply for confirmatory testing.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Weekly

7 – 10 Days

• Keep specimen cold during transit, but do not ship on dry ice. 
• Please contact Client Services at (855) 535-1522 for shipping kits and instructions.
• Use the cold pack provided in the KDL shipping kit. 
• Ship the specimen overnight express, using the FedEx priority overnight label provided.