• Test code: 06104
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Elevated C0/(C16+C18) Test

Test description

The Invitae Elevated C0/(C16+C18) Test analyzes the CPT1A gene, which is associated with elevations of the C0/(C16+C18) acylcarnitine ratio on newborn screening (NBS) or plasma acylcarnitine analysis. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (1 gene)

Alternative tests to consider

The Invitae Fatty Acid Oxidation Defects Panel has been designed to provide a broad genetic analysis of fatty acid oxidation defects. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.

  • carnitine palmitoyltransferase I (CPT1) deficiency

Carnitine palmitoyltransferase I (CPT1) deficiency can lead to elevated C0/(C16+C18) acylcarnitine ratio that may be detected during newborn screening or acylcarnitine analysis. Patients with this disorder typically present in early childhood with episodes of hypoketotic hypoglycemia and hepatic encephalopathy during periods of intercurrent illness or increased fasting. Free fatty acids and liver transaminases may be elevated during attacks, but they may also be elevated during asymptomatic periods. Cardiac- and skeletal-muscle involvement is uncommon. Some patients may develop hepatomegaly and renal tubular acidosis. Some cases of sudden infant death syndrome (SIDS) have been attributed to CPT1 deficiency. Milder forms of CPT1 deficiency have been reported.

A low-fat diet with medium-chain triglyceride (MCT) supplementation and an avoidance of fasting have been used to treat patients with CPT1 deficiency. Early diagnosis and detection may improve the long-term outcome of these patients by reducing or preventing attacks of hepatic encephalopathy.

Pregnant females (obligate carriers) of fetuses affected with CPT1 deficiency are at increased risk of developing acute fatty liver of pregnancy. Symptomatic mothers may develop hypoglycemia, elevated LFTs, and hyperammonemia, leading to impaired liver function and coagulopathy.

For patients with biochemical features consistent with CPT1 deficiency (elevated C0/[C16+C18] on acylcarnitines or elevated free-to-total plasma carnitine ratio), approximately >99% will have two pathogenic variants in CPT1A.

CPT1 deficiency is inherited in an autosomal recessive manner.

The prevalence of elevated C0/(C16+C18) acylcarnitine ratio is dependent on laboratory cutoffs and ethnicity. The overall prevalence of CPT1 deficiency is very rare. The frequency of a mild form of CPT1 is high among the Canadian and Greenland Inuit, BC First Nations, and Alaska Natives populations; it has been estimated in at least 1 in 400 individuals.

This test may be appropriate for:

  • patients who have an elevated C0/(C16+C18) acylcarnitine ratio on newborn screening or plasma acylcarnitine analysis, or an elevated free-to-total carnitine ratio in plasma
  • pregnant females with acute fatty liver of pregnancy

For considerations for testing please refer to:

  1. Borch, L, et al. Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples from a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark. JIMD Rep. 2012; 3:11-5. PMID: 23430868
  2. Longo, N, et al. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006; 142C(2):77-85. PMID: 16602102
  3. Collins, SA, et al. Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in Yukon, Northwest Territories, and Nunavut. Mol. Genet. Metab. 2010; 101(2-3):200-4. PMID: 20696606
  4. Rajakumar, C, et al. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I. J. Lipid Res. 2009; 50(6):1223-8. PMID: 19181627
  5. Greenberg, CR, et al. The paradox of the carnitine palmitoyltransferase type Ia P479L variant in Canadian Aboriginal populations. Mol. Genet. Metab. 2009; 96(4):201-7. PMID: 19217814
  6. Bennett, MJ, Santani, AB. Carnitine Palmitoyltransferase 1A Deficiency. 2005 Jul 27. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301700
  7. American College of Medical Genetics. NBS ACT Sheet. Carnitine Palmitoyl Transferase 1 Deficiency. https://www.acmg.net/StaticContent/ACT/C0_C16-C18.pdf Accessed February 2016.
  8. Baby's first test. Newborn screening. http://www.babysfirsttest.org/ Accessed February 2016.
  9. Morris AMA, Spiekerkoetter U. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 13, Disorders of mitochondrial fatty acid oxidation and related metabolic pathways; p. 201–216.
  10. Wilcken B, Rinaldo P, Matern D. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 3, Newborn screening for inborn errors of metabolism; p. 75–86.
  11. Feuchtbaum, L, et al. Birth prevalence of disorders detectable through newborn screening by race/ethnicity. Genet. Med. 2012; 14(11):937-45. PMID: 22766612

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CPT1A NM_001876.3