Glutaric Acidemia Type I via the GCDH Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
210 GCDH$790.00 81406 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
Schwartz et al. (Hum Genet 102:452-458, 1998) detected 95% of GCDH mutations 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. (J Med Genet 37:177-181, 2000) reported finding 100% of causative alleles among 48 patients diagnosed with GA I by biochemical studies.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GCDH$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

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 and/or gastrointestinal infection 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.
Glutaric Acidemia Type I is an autosomal recessive disorder.  Over 100 pathogenic mutations have been reported in the GCDH gene with the majority being missense changes.  Relatively fewer nonsense, splice site, and small insertion/deletion mutations are reported.  Mutations are found in every GCDH exon (Goodman et al. Hum Mut 12:141-4, 1998).  A founder mutation (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 mutation appears to be the p.Arg402Trp missense change found among people of German descent.  In German GA I patients, this mutation accounts for about 40% of alleles (Zschocke et al. J Med Genet 37:177-181, 2000).
Testing Strategy
This test involves bidirectional DNA sequencing of all 11 coding exons of the GCDH gene.  The entire coding region and ~10 bp of flanking non-coding DNA on either side of each splice site are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.
Indications for Test
Patients suspected of having GA I based on biochemical testing and/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.


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


Name Inheritance OMIM ID
Glutaric Aciduria, Type 1 231670


Genetic Counselors
  • Goodman, S. I., (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., (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., (2005). "Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency." Neurology 64(12): 2142-4. PubMed ID: 15985591
  • Morton, D. H., (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., (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., (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., (2000). "Mutation analysis in glutaric aciduria type I." J Med Genet 37(3): 177-81. PubMed ID: 10699052
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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