• Test code: 06112
  • 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 C5-OH Panel

Test description

The Invitae Elevated C5-OH Panel analyzes 13 genes that are associated with elevations of C5-OH acylcarnitine on newborn screening (NBS) or plasma acylcarnitine analysis. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

Order test

Primary panel (13 genes)


Alternative tests to consider

The Invitae Organic Acidemias Panel has been designed to provide a broad genetic analysis of this class of disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.

  • 2-methyl-3-hydroxybutyric aciduria (2M3HBA)
  • 3-hydroxy-3-methylglutaryl-CoA lyase (3HMG) deficiency
  • 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency
  • 3-methylglutaconyl-CoA hydratase (3MGA) deficiency
  • beta-ketothiolase deficiency
  • Barth syndrome
  • biotinidase deficiency
  • CLPB defect causing 3-methylglutaconic aciduria
  • Costeff syndrome
  • dilated cardiomyopathy with ataxia syndrome
  • holocarboxylase synthetase deficiency
  • Megdel syndrome

Elevated C5-OH acylcarnitine may be detected during NBS or plasma acylcarnitine analysis due to multiple inherited disorders. One group of disorders leads to defects in the metabolism of leucine or isoleucine—two of the branched-chain amino acids. Another group of disorders results from deficiency of the cofactor biotin, which is necessary for the proper function of the biotin-dependent carboxylases. Most of the biotin-dependent carboxylases are also involved in branched-chain amino acid metabolism. Barth syndrome can also lead to elevations of branched-chain amino acid intermediates, resulting in elevated C5-OH on NBS or plasma acylcarnitine analysis. The last group of disorders leads to secondary elevations of 3-methylglutaconic acid, which can also result in elevated C5-OH. Some healthy neonates may have abnormal elevation of C5-OH on NBS due to 3MCC deficiency in the mother.

Patients with elevated C5-OH may present with a wide range of symptoms that depend on the underlying genetic cause. Some disorders, such a 3-HMG-CoA lyase deficiency, can cause a very severe presentation within the first days of life. In contrast, most patients with 3MCC deficiency typically remain asymptomatic despite the presence of the biochemical abnormalities. Many of these disorders have some treatment, such as dietary therapy. Early diagnosis is critical in determining the severity of the underlying disorder to avoid irreversible damage and improve long-term outcomes.

This panel covers all known genetic conditions that can cause elevated C5-OH on newborn screening or acylcarnitine analysis.

Most genetic causes of elevated C5-OH are inherited in an autosomal recessive manner. Barth syndrome and 2-methyl-3-hydroxybutyric aciduria are inherited in an X-linked manner.

The prevalence of elevated C5-OH is dependent on laboratory cutoffs and ethnicity. Limited data exist on the rates of false-positive elevations of C5-OH in the NBS setting. The prevalence of confirmed genetic causes of elevated C5-OH has been reported as high as 1 in 3,300 in some ethnic groups.

This panel may be appropriate for:

  • infants with elevated C5-OH on NBS or confirmatory plasma acylcarnitine analysis
  • patients with elevated C5-OH on plasma acylcarnitine analysis with unclear or unavailable urine organic acid results

For considerations for testing please refer to:

  1. American College of Medical Genetics. NBS ACT Sheet. Organic Acidemias. https://www.acmg.net/StaticContent/ACT/C5-OH.pdf Accessed February 2016.
  2. Ferreira, C, et al. Barth Syndrome. 2014 Oct 09. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK247162/ PMID: 25299040
  3. Lamari F, Sédel F, Saudubray J-M. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 35, Disorders of phospholipid synthesis; p. 485–498.
  4. Wortmann, SB, et al. CLPB Deficiency. 2016 Nov 22. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 27891836
  5. Wolf, B. Biotinidase Deficiency. 2000 Mar 24. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301497
  6. Baby's first test. Newborn screening. http://www.babysfirsttest.org/ Accessed February 2016.
  7. Baumgartner MR, Suormala T. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 27, Biotin-responsive disorders; p. 375–384.
  8. 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.
  9. Schiff M, Ogier de Baulny H, Dionisi-Vici C. Inborn metabolic diseases: diagnosis and treatment. 6th ed. Heidelberg: Springer; 2016. Chapter 18, Branched-chain organic acidurias/acidaemias; p. 289–293.
  10. 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
ACAT1 NM_000019.3
AUH NM_001698.2
BTD NM_000060.3
CLPB NM_030813.5
DNAJC19 NM_145261.3
HLCS NM_000411.6
HMGCL NM_000191.2
HSD17B10 NM_004493.2
MCCC1 NM_020166.4
MCCC2 NM_022132.4
OPA3 NM_025136.3
SERAC1 NM_032861.3
TAZ NM_000116.4