Glutaric Aciduria Type I (GA-I): GCDH Gene Deletion/Duplication

Condition Description

Glutaric aciduria type I (GA-I) is an autosomal recessive inborn error of lysine, hydroxylysine, and tryptophan metabolism caused by deficiency of the enzyme glutaryl-CoA dehydrogenase [1]. Frequent laboratory findings include hypoglycemia, ketonuria, and metabolic acidosis. Urinary 3-hydroxyglutaric acid is the diagnostic metabolite with glutaric acid and glutarylcarnitine frequently but not always elevated [2]. The buildup of metabolites may lead to basal ganglia injury.

The clinical manifestations of GA-1 can vary considerably between individual patients, but most have macrocephaly at birth or shortly thereafter. Affected individuals may experience motor difficulty, abnormal gait, spasms, jerking, rigidity, hypotonia, and seizures. Some individuals with glutaric acidemia have developed subdural or retinal hemorrhage. MRI or CT of the brain may show an underdeveloped neocortex with fronto-operculo-temporal hypoplasia and communicating hydrocephalus, creating a distinct radiologic appearance that characterizes GA-I. The presentation of distinctive acute striatal necrosis is a major cause of morbidity and mortality. Acute neurological deterioration usually occurs between 6 and 18 months of age and can be triggered by a febrile illness or dehydration.

GA-1 is caused by mutations in the glutaryl-CoA dehydrogenase gene (GCDH) located on 19p13 [3]. Gene sequence analysis is available to test for mutations in the GCDH gene (FX).


  • Hedlund GL, Longo N, Pasquali M. Glutaric acidemia type 1. Am J Med Genet Part C Semin Med Genet 2006, 142C:86-94.
  • Tortorelli et al. The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric acidemia type I. Mol Genet Metab 84 (2005) 137-143.
  • Goodman et al. Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): Review and report of thirty novel mutations. Hum Mutat 1998, 12:141-144.
  • Korman et al. Glutaric aciduria type 1: Clinical, biochemical and molecular findings in patients from Israel. Eur J Ped Neurol 2007, 11:81-89.
  • Schwarz et al. The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type 1. Hum Genet 1998;102:452-8.
  • Schulze et al. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics 2003, 111(6 Pt 1):1399-406.

Genes (1)


This test is indicated for:
  • Confirmation of a clinical/biochemical diagnosis of GA-I
  • Carrier testing in adults with a family history of GA-I


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.
Prevalence: The incidence of GA-I is estimated to be 1:83,300 [6]. It is inherited in an autosomal recessive manner, therefore the recurrence risk for carrier parents of an affected child is 25%.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside EGL Genetics, please submit a copy of the sequencing report with the test requisition. Contact the laboratory if further information is needed.
  • Urine Organic Acid Analysis (OA) showing elevation of glutaric and 3-hydroxyglutaric acids
  • Plasma/Urine Acylcarnitine Profile showing increased concentration of glutarylcarnitine.
  • Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
  • Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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