Carnitine-acylcarnitine translocase deficiency is a rare autosomal recessive disorder of fatty acid oxidation. CACT is the second component of the carnitine shuttle for the import of long-chain fatty acids from the cytosol into the mitochondrion where they undergo ??-oxidation. It is an inner mitochondrial membrane protein which mediates the transport of acylcarnitine esters into the mitochondrial matrix in exchange for free carnitine.
CACT deficiency is, together with infantile carnitine palmitoyltransferase II (CPT2) deficiency, the most severe of the mitochondrial fatty acid oxidation defects. The pathogenesis of the disorder is a combination of the deficient production of energy from mitochondrial fatty acid oxidation and the toxicity of accumulating long-chain acylcarnitines. It usually presents in the early newborn period, with a high mortality at the initial presentation or during the first year of life. The typical features include cardiomyopathy, arrhythmias, hepatic dysfunction, skeletal muscle damage, hyperammonemia, hypoketotic hypoglycemia with dicarboxylic aciduria, elevation of long-chain acylcarnitines, and deficiency of free carnitine. A minority of patients have a later onset with a milder clinical phenotype. In a significant proportion of cases, the presentation is as sudden, unexpected death, presumably due to an arrhythmia.
CACT deficiency is caused by mutations in the SLC25A20 gene (3p21.31).
For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array (HR).
Reference: Korman, SH et al. A novel SLC25A20 splicing mutation in patients of different ethnic origin with neonatally lethal carnitine-acylcarnitine translocase (CACT) deficiency. Molec. Genet. Metab. 2006, 89(4):332-338.
- OMIM #212138: Carnitine-Acylcarnitine Translocase Deficiency
- Confirmation of a clinical/biochemical diagnosis of CACT deficiency
- Carrier testing in adults with a family history of CACT deficiency
Analytical Sensitivity: ~99%
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by sequencing.
- A deletion/duplication assay is available separately for individuals where mutations are not identified by sequence analysis. Refer to the test requisition or contact the laboratory for more information.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.