Carnitine-Acylcarnitine Translocase Deficiency via the SLC25A20 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11859 SLC25A20 81405 81405,81404 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11859SLC25A2081405 81404(x1), 81405(x1) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder of long-chain fatty acid oxidation (Vitoria et al. 2015; Murphy et al. 2016). CACT deficiency most commonly presents as a severe neonatal disorder, though a small proportion of patients may present later with more mild disease (Iacobazzi et al. 2004; Korman et al. 2006; Vitoria et al. 2015). Patients with severe CACT deficiency present with cardiomyopathy and cardiac arrhythmias that can lead to sudden death, muscle weakness, hypotonia, respiratory distress, seizures, hepatomegaly, lethargy, and possible coma. Episodic attacks of hypoketotic hypoglycemia with hyperammonemia, metabolic acidosis, increased creatine phosphokinase (CPK) levels and elevated transaminases are observed, and are often triggered by fasting or illness. Patients may also exhibit dicarboxylic acidurias well as low levels of free carnitine and an abnormal acylcarnitine profile, particularly with increased C16-18 acylcarnitines (Huizing et al. 1997; Vitoria et al. 2015; Murphy et al. 2016). Later onset patients may range from mildly symptomatic to asymptomatic (Iacobazzi et al. 2004; Vitoria et al. 2015).

Management of the disorder typically involves limiting dietary long-chain triglycerides, supplementation with medium-chain triglycerides and other essential fatty acids, prevention of fasting, especially during illness, and treatment of symptoms (Vitoria et al. 2015; Murphy et al. 2016).

Genetics

CACT deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the SLC25A20 gene. Approximately 40 pathogenic variants have been reported to date. Approximately half of the pathogenic variants are missense or in-frame deletions or insertions, followed by small frameshift deletions or insertions (~30%), splice variants (~15%) and nonsense variants (~10%) (Human Gene Mutation Database). Two variants have been reported to be more prevalent than others: c.199-10T>G is common in East Asian populations and p.Gln238Arg is common in Arab patients (Vitoria et al. 2015). There may be some level of genotype-phenotype correlation, with more severely affected patients having a lower level of residual CACT enzyme activity and mildly affected patients having a higher level of residual enzyme activity, although this does not always seem to be the case (Vitoria et al. 2015).

The SLC25A20 gene encodes the carnitine-acylcarnitine translocase (CACT) protein, which is part of the carnitine shuttle. CACT functions by exchanging long-chain acylcarnintine esters that were generated via the action of carnitine palmitoyltransferase 1 (CPT1) for carnitine. This results in the transport of acylcarnitines across the inner mitochondrial membrane into the mitochondrial matrix, where they are converted back to acyl-CoAs via the action of carnitine palmitoyltransferase 2 (CPT2) (Murphy et al. 2016).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity of SLC25A20 gene sequencing is expected to be high for patients with carnitine-acylcarnitine translocase deficiency, as to date, nearly all reported patients have had two pathogenic variants detectable via sequencing. Based on a collective total of several studies, 75 alleles were reported in 38 unique patients, for a clinical sensitivity of ~99% (Huizing et al. 1997; Ogawa et al. 2000; Yang et al. 2001; Costa et al. 2003; Iacobazzi et al. 2004; Korman et al. 2006; Wang et al. 2011; Fukushima et al. 2013; Vatanavicharn et al. 2015; Vitoria et al. 2015). The one allele not detectable via sequencing was a large, multi-exon deletion (Wang et al. 2011).

It is difficult to precisely estimate the clinical sensitivity of this test as to date, only one confirmed gross deletion has been reported in the SLC25A20 gene (Wang et al. 2011), and no gross insertions have been reported. However, the clinical sensitivity appears to be relatively low.

Testing Strategy

This test provides full coverage of all coding exons of the SLC25A20 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

In addition to the regions described above, this testing includes coverage for the reported intronic c.843+4_843+50del pathogenic variant (Iacobazzi et al. 2004).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with positive newborn screen results for carnitine deficiency as well as those with clinical and biochemical test results consistent with CACT deficiency are good candidates for this test. Family members of patients who have known SLC25A20 pathogenic variants are also good candidates. We will also sequence the SLC25A20 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
SLC25A20 613698
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Carnitine-Acylcarnitine Translocase Deficiency AR 212138

Citations

  • Costa C. et al. 2003. Molecular Genetics and Metabolism. 78: 68-73. PubMed ID: 12559850
  • Fukushima T. et al. 2013. Journal of Human Genetics. 58: 788-93. PubMed ID: 24088670
  • Huizing M. et al. 1997. American Journal of Human Genetics. 61: 1239-45. PubMed ID: 9399886
  • Human Gene Mutation Database (Bio-base).
  • Iacobazzi V. et al. 2004. Human Mutation. 24: 312-20. PubMed ID: 15365988
  • Korman S.H. et al. 2006. Molecular Genetics and Metabolism. 89: 332-8. PubMed ID: 16919490
  • Murphy et al. 2016. Fatty Acid Oxidation, Electron Transfer and Riboflavin Metabolism Defects. In: Hollak and Lachmann, editors. Inherited Metabolic Disease in Adults: A Clinical Guide. New York: Oxford University Press, p 55-67.
  • Ogawa A. et al. 2000. Journal of Human Genetics. 45: 52-5. PubMed ID: 10697964
  • Vatanavicharn N. et al. 2015. Brain & Development. 37: 698-703. PubMed ID: 25459972
  • Vitoria I. et al. 2015. Jimd Reports. 20: 11-20. PubMed ID: 25614308
  • Wang G.L. et al. 2011. Molecular Genetics and Metabolism. 103: 349-57. PubMed ID: 21605995
  • Yang B.Z. et al. 2001. Molecular Genetics and Metabolism. 73: 64-70. PubMed ID: 11350184

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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