Genes Tested

CPT2, SLC25A20

Disease

Carnitine palmitoyltransferase II deficiency (CPT2 gene); Carnitine-acylcarnitine translocase deficiency (SLC25A20 gene)

Description

Pathogenic variants in CPT2 and SLC25A20 cause fatty acid oxidation disorders that can present in a similar manner in infancy with hypoketotic hypoglycemia, hepatic dysfunction, cardiomyopathy, and other features. CPT2 encodes carnitine palmitoyltransferase II (CPT II) and SLC25A20 encodes carnitine-acylcarnitine translocase (CACT). Both of these are part of the carnitine cycle, which is necessary for transport of long-chain fatty acids from cytosol to mitochondria for beta-oxidation. Both CPT II deficiency and CACT deficiency can cause increased concentrations of 16-2 palmitoylcarnitine on acylcarnitine profile, making it difficult to differentiate between the two conditions. For both conditions, presentations at a later age with a milder phenotype have been reported. 

Indications

Hypoketotic hypoglycemia
Hyperammonemia
Rhabdomyolysis
Hepatic dysfunction
Cardiomyopathy/ arrhythmias
Encephalopathy 
Elevated 16-2 palmitoylcarnitine on acylcarnitine profile

Testing Methodology 

PCR-based sequencing of entire coding region, intron/exon boundaries, as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the specified gene(s).

Sensitivity and Limitations

The analytical sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions/ duplications, large insertions and other complex genetic events will not be identified using sequencing methodology.

Turn-Around Time

7 days

CPT Codes

81405

How to Order

Testing for these genes is also available as part of the Metaboseq panel by next-generation sequencing. Deletion/duplication analysis and targeted variant analysis is also available for these genes. Download Inborn Errors of Metabolism requisition.

References

Deschauer, M, Wieser, T, et al. (2005) Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects. Arch. Neurol. 62: 37-41.

Illsinger, S, Lucke, T, et al. (2008) Carnitine-palmitoyltransferase 2 deficiency: novel mutations and relevance of newborn screening. Am. J. Med. Genet. 146A: 2925-2928. 

Iacobazzi, V, Invernizzi, F, et al. (2004) Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency. Hum. Mutat. 24: 312-320.

Isackson, PJ, Bennett, MJ, et al. (2008) CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency. Molec. Genet. Metab. 94: 422-427.

Longo, N, di San Filippo, CA, et al. (2006) Disorders of carnitine transport and the carnitine cycle. Am. J. Med. Genet. 142C: 77-85.

Rubio-Gozalbo, ME, Bakker, JA, et al. (2004) Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects. Mol. Aspects Med. 25: 521-532.