Glutaric Acidemia Type I 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
9617 GCDH 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9617GCDH81406 81406(x1), 81479(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

Clinical Features and Genetics

Clinical Features

Glutaric acidemia type I (GA I; OMIM 231670) is an inborn error of metabolism resulting from glutaryl-CoA dehydrogenase (GCDH) deficiency. Patients with GA I suffer injury to the basal ganglia and develop severe, life threatening dystonia, and choreoathetosis (Strauss et al. Am J Med Genet 121C:38-52, 2003). Macrocephaly may be the only presenting feature at birth, and the extent of basal ganglia degeneration determines functional disability. GA I patients often present with an acute encephalopathic crisis, mostly associated with an upper respiratory or gastrointestinal infection or both early in life (Hoffmann et al. J Inher Metab Dis 18:173-176, 1995). Typical onset of symptoms is in infancy, although variability of age at onset occurs (Morton et al. Am J Med Genet 41:89-95, 1991). Some individuals remain asymptomatic. Patients with adult onset have been shown to respond effectively to therapy (Kulkens et al. Neurology 64:2142-2144, 2005). Biochemically, GA I patients have elevated glutaric acid and 3-OH-glutaric acid in urine and elevated glutarylcarnitine in blood. Unlike other organic acidemias, ketosis and acidosis are not features of GA I.

Genetics

Glutaric acidemia type I is an autosomal recessive disorder. Over 100 pathogenic variants have been reported in the GCDH gene with the majority being missense changes. Relatively fewer nonsense, splice site, and small insertion/deletion variants are reported. Variants are found in every GCDH exon (Goodman et al. Hum Mut 12:141-4, 1998). A founder variant (p.Ala421Val) exists in the Old Order Amish of Lancaster County, Pennsylvania with a carrier frequency of approximately 0.10 (Morton et al. Am J Med Genet 41:89-95, 1991). Another founder variant appears to be the p.Arg402Trp missense change found among people of German descent. In German GA I patients, this variant accounts for about 40% of alleles (Zschocke et al. J Med Genet 37:177-181, 2000).

Clinical Sensitivity - Sequencing with CNV PGxome

Schwartz et al. detected 95% of GCDH variants among 20 GA I patients from various European countries. The SSCP gel-based method to detect sequence variants in this report is likely less sensitive than direct DNA sequencing. Similarly, Zschocke et al. reported finding 100% of causative alleles among 48 patients diagnosed with GA I by biochemical studies.

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 suspected of having GA I based on biochemical testing or clinical features. All patients with reduced glutaryl-CoA dehydrogenase 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

Citations

  • Goodman, S. I., et.al. (1998). "Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations." Hum Mutat 12(3): 141-4. PubMed ID: 9711871
  • Hoffmann, G. F., et.al. (1995). "Early signs and course of disease of glutaryl-CoA dehydrogenase deficiency." J Inherit Metab Dis 18(2): 173-6. PubMed ID: 7564239
  • Kulkens, S., et.al. (2005). "Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency." Neurology 64(12): 2142-4. PubMed ID: 15985591
  • Morton, D. H., et.al. (1991). "Glutaric aciduria type I: a common cause of episodic encephalopathy and spastic paralysis in the Amish of Lancaster County, Pennsylvania." Am J Med Genet 41(1): 89-95. PubMed ID: 1951469
  • Schwartz, M., et.al. (1998). "The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I." Hum Genet 102(4): 452-8. PubMed ID: 9600243
  • Strauss, K. A., et.al. (2003). "Type I glutaric aciduria, part 1: natural history of 77 patients." Am J Med Genet C Semin Med Genet 121C(1): 38-52. PubMed ID: 12888985
  • Zschocke, J., et.al. (2000). "Mutation analysis in glutaric aciduria type I." J Med Genet 37(3): 177-81. 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


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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