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Elevated C5-DC Acylcarnitine via the GCDH 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
GCDH 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
16037GCDH81406 81406,81479 $990 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 platform).

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

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

Newborn screening (NBS) tests are performed soon after birth with the goal of identifying individuals that may be affected by certain disorders before disease-related disability or death occurs. Appropriate medical management beginning early in life can prevent all or many symptoms in the affected individuals (Watson et al. 2006. PubMed ID: 16783161; https://www.cdc.gov/newbornscreening/). While NBS is required within all states and territories in the United States, individual state or territory public health departments determine which conditions are included on the NBS panel (https://www.babysfirsttest.org/newborn-screening/states). NBS protocols outside of the United States vary from country to country. At a minimum, all core conditions on the Recommended Uniform Screening Panel (RUSP) should be included on NBS panels within the United States. In addition, NBS testing may also include secondary conditions, which are disorders that can be detected as part of the differential diagnosis of a core condition (https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp). Following an abnormal NBS result, follow up diagnostic testing is indicated. Such testing may include biochemical methodologies (for example, urine organic acid analysis or plasma acylcarnitine analysis), enzyme assays, and/or molecular genetic testing.

This test is designed for individuals with NBS results showing elevated C5-DC acylcarnitine, which can indicate a deficiency of the glutaryl-CoA dehydrogenase (GCDH) enzyme. GCDH deficiency is a core condition on the RUSP. 

Individuals with GCDH deficiency may be unaffected during the newborn period but are at risk of acute encephalopathic crises triggered by common illnesses (Hoffmann et al. 1995. PubMed ID: 7564239; https://www.acmg.net/PDFLibrary/C5-DC.pdf). The overall prevalence of GCDH deficiency is estimated at ~1/100,000 worldwide, though it can be significantly higher in certain populations (Kölker et al. 2007. PubMed ID: 17622945; Larson and Goodman 2019. PubMed ID: 31536184). 

Genetics

Glutaryl-CoA dehydrogenase (GCDH) deficiency, also known as glutaric acidemia type I, is an autosomal recessive disorder. Over 350 pathogenic variants have been reported in the GCDH gene in the HGMD and ClinVar databases (https://www.hgmd.cf.ac.uk/; https://www.ncbi.nlm.nih.gov/clinvar/), with the majority being missense changes. Relatively fewer nonsense, splice site, and small insertion/deletion variants are reported, and copy number variants (CNVs) have only rarely been reported (Larson and Goodman 2019. PubMed ID: 31536184). Variants are found in every GCDH exon (Goodman et al. 1998. PubMed ID: 9711871). Several founder variants have been reported in a variety of populations: the Ojibway-Cree First Nations Canadians (c.91+5G>T), the South African Xhosa population (c.877G>A, p.Ala293Thr), the Irish Traveler communities in the Republic of Ireland (c.1093G>A, p.Glu365Lys), the Lumbee Native Americans of North Carolina (c.1240G>A, p.Glu414Lys), and the Pennsylvania Amish (c.1262C>T, p.Ala411Val) (Larson and Goodman 2019. PubMed ID: 31536184). Several other variants are also common in individuals from a variety of populations: c.680G>C, p.Arg227Pro; c.1198G>A, p.Val400Met; c.1213A>G, p.Met405Val; c.541G>C, p.Glu181Gln; c.1204C>T, p.Arg402Trp (Larson and Goodman 2019. PubMed ID: 31536184). The most common pan-ethnic variant, c.1204C>T, p.Arg402Trp, is reported in the gnomAD database with a maximum minor allele frequency of 0.076% (https://gnomad.broadinstitute.org/). To our knowledge, de novo variants in GCDH have not been reported. 

Pathogenic variants in the GCDH gene lead to disruption of the glutaryl-CoA dehydrogenase enzyme, which is an enzyme in the lysine degradation pathway. Deficiency of this enzyme results in elevation of glutaric acid, glutarylcarnitine (C5-DC), and other toxic metabolites (https://www.acmg.net/PDFLibrary/C5-DC.pdf; http://www.iembase.com/disorder/163).

Clinical Sensitivity - Sequencing with CNV PGxome

Based on studies of individuals with a diagnosis of glutaric acidemia type I, approximately 95-100% of expected GCDH variants are identified by molecular testing (Schwartz et al. 1998. PubMed ID: 9600243; Zschocke et al. 2000. PubMed ID: 10699052; Mosaeilhy et al. 2017. PubMed ID: 28389991; Larson and Goodman 2019. PubMed ID: 31536184; Kilavuz et al. 2021. PubMed ID: 33578440). 

Testing Strategy

This test provides full coverage of all coding exons of the GCDH 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).

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 elevated C5-DC acylcarnitine on NBS are good candidates for this test. Patients with reduced glutaryl-CoA dehydrogenase enzyme activity are candidates for this test. We will also sequence the GCDH gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
GCDH 608801
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Glutaric Aciduria, Type 1 AR 231670

Related Tests

Name
Glutaric Acidemia Type I via the GCDH Gene
PGmaxTM - Comprehensive Inherited Metabolic Disorders and Mitochondrial Disorders (Nuclear Genes only) Panel

Citations

  • Goodman et al. 1998. PubMed ID: 9711871
  • Hoffmann et al. 1995. PubMed ID: 7564239
  • http://www.iembase.com/disorder/163
  • https://gnomad.broadinstitute.org/
  • https://www.acmg.net/PDFLibrary/C5-DC.pdf
  • https://www.babysfirsttest.org/newborn-screening/states
  • https://www.cdc.gov/newbornscreening/
  • https://www.hgmd.cf.ac.uk/
  • https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp
  • https://www.ncbi.nlm.nih.gov/clinvar/
  • K├Âlker et al. 2007. PubMed ID: 17622945
  • Kilavuz et al. 2021. PubMed ID: 33578440
  • Larson and Goodman 2019. PubMed ID: 31536184
  • Mosaeilhy et al. 2017. PubMed ID: 28389991
  • Schwartz et al. 1998. PubMed ID: 9600243
  • Watson et al. 2006. PubMed ID: 16783161
  • Zschocke et al. 2000. PubMed ID: 10699052

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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2) Select Additional Test Options

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