Glutaric Acidemia Type 1
Glutaric Acidemia Type 1 (GA-1) is an autosomal recessive deficiency
of the glutaryl-coA dehydrogenase enzyme, which is encoded by the
GCDH gene.
PrintGlutaric Acidemia Type 1 (GA-1) is an autosomal recessive deficiency
of the glutaryl-coA dehydrogenase enzyme, which is encoded by the
GCDH gene.
Macrocephaly in early infancy may be the only sign of Glutaric Acidemia Type 1 until the occurrence of a neurological crisis. Atrophy and neuronal loss follow the initial injury to the basal ganglia and become evident as dystonia, spasticity, rigidity, posturing, and other complications that impair feeding, mobility, and communication. Asymptomatic patients, insidious-onset cases without crises, late childhood onset cases, and rare adult-onset cases have been described.
Diagnosis of Glutaric Acidemia Type 1 is made by measurement of organic acids in blood and urine, enzyme analysis (most often in cultured fibroblasts), and/or by DNA analysis. DNA analysis is recommended as an appropriate test to follow up a newborn screen positive for GA-1.
The Ambry Test: Glutaric Acidemia Type 1 is a Gene Sequencing Analysis test that detects approximately 99% of GCDH mutations and is appropriate for carrier or diagnostic testing. GCDH Genetic Testing can be done on a simple blood or saliva specimen, it provides a timely, highly sensitive, and much less invasive alternative to enzyme analysis on skin biopsy.
Glutaric Acidemia Type 1 (GA-1) is an autosomal recessive deficiency of the glutaryl-coA dehydrogenase enzyme which acts in amino acid metabolism. Macrocephaly in early infancy may be the only presenting sign until the occurrence of a neurological crisis marked by spasms, hypotonia, and lethargy. This episode usually occurs between the ages of three and 36 months and may be precipitated by febrile illness, surgery, or immunization. Patients remain at risk for subdural and retinal hemorrhages. Atrophy and neuronal loss follow the initial injury to the basal ganglia and become evident as dystonia, spasticity, rigidity, posturing, and other complications that impair feeding, mobility, and communication. Intelligence may be unaffected. Asymptomatic patients, insidious-onset cases without crises, late childhood onset cases, and rare adult-onset cases have been described.1
Diagnosis is made by measurement of elevated glutaric and 3-hydroxyglutaric acids in blood and urine, enzyme analysis (most often in cultured fibroblasts), and/or by DNA analysis.While genotype generally correlates with residual enzyme activity and the biochemical profile, none reliably predict the clinical phenotype of this variable disease.1- 3 Early diagnosis followed with dietary restriction of lysine intake, carnitine supplementation, and emergency care protocols during illness and other periods of vulnerability have prevented encephalopathic crises and clinically evident brain injury in over two-thirds of cases. 3-4 Due to the value of an early and accurate diagnosis, newborn screening is widely implemented. DNA analysis is recommended as one of the appropriate tests to follow up a newborn screen positive for GA-1.5 The disease occurs in approximately 1/100,000 births in the general population5 and in up to 1/300 in certain genetic isolates including Old Order Amish of Pennsylvania, Canadian Ojibway-Cree Indians, and the Irish Travellers.
The Ambry Test can be done on a simple blood or saliva specimen collected from a patient of any age, providing a timely, highly sensitive, and much less invasive alternative to enzyme analysis on skin biopsy. Full gene analysis is appropriate for the following indications:
- known or suspected Glutaric Acidemia Type 1
- diagnostic confirmation after abnormal or ambiguous newborn screen results
- carrier status determination for relatives of patients with known mutations
- prenatal diagnosis for carrier couples
The Ambry Test: Glutaric Acidemia Type 1 is performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-11 of the GCDH gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis for individual GCDH mutations known to be in the family is
also available.
Approximately 99% of GCDH mutations are detectable by the Ambry Test: Glutaric Acidemia Type 1.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes | |
|---|---|---|---|
| 1600 | GCDH Gene Sequence Analysis | 83891x1, 83894x9, 83898x8, 83904x16, 83909x16, 83912x1 |
| Technique | Days |
|---|---|
| GCDH Gene Sequence Analysis | 10-21 |
1 Funk CBR et al. Brain. 2005;128:711-722.
2 Hedlund GL et al.Am J Hum Genet C Semin Med Genet. 2006;142(2):86-94.
3 Kolker S et al. Ped Research. 2006;59(6):840-847.
4 Kolker S et al. Ann Neurol. 2004;55:7-12.
5 Kolker S et al. J Inherit Metab Dis. 2007;30:5-22.