Glutaric Acidemia Type 1 (GA-1) is an autosomal recessive deficiency of the glutaryl-coA dehydrogenase enzyme which acts in the catabolism of lysine, hydroxylysine, and tryptophan. The disease occurs in approximately 1/100,000 births in the general North American population and in up to 1/300 in certain genetic isolates including Old Order Amish of Pennsylvania, Canadian Ojibway-Cree Indians, and the Irish Travellers.

Diagnosis is made by enzyme analysis (usually in cultured fibroblasts), measurement of elevated glutaric and 3-hydroxyglutaric acids in blood and urine, and/or by DNA analysis. While genotype generally correlates with residual enzyme activity and the biochemical profile, neither predict the clinical phenotype of this variable disease. Genetic testing enables diagnostic confirmation in patients with consistent or ambiguous biochemical results, carrier status determination in studied families, and the option of prenatal diagnosis.

The Ambry Test is full gene sequence analysis of the GCDH gene. Results are reported 14-21 days after testing is initiated.

Macrocephaly in early infancy may be the only presenting sign of GA-1 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, opisthotonos, spasticity, and other complications that impair feeding, mobility, and communication. Intelligence may be relatively preserved.

Asymptomatic patients, insidious-onset cases without crises, late childhood onset cases, and rare adult-onset cases have been described.

Most patients can be identified by newborn screening for GA-1. 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 2/3 of cases.

General Test Information
   The Ambry Test: Glutaric Acidemia Type 1
    (Abobe PDF document)

The following CPT Codes for the Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: Glutaric Acidemia Type 1
83891, 83894, 83898, 83904, 83909, 83912

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

Disclaimer:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. The Ambry Test: Glutaric Acidemia Type 1 analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, and small indels. It is not intended to analyze the following types of mutations: gross insertions, gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: Glutaric Acidemia Type 1 is designed and validated to be capable of detecting ~99% of described GCDH mutations (considering less than 1% to be the other types of mutations). Glutaric Acidemia Type 1 is a complex clinical disorder which in most cases is due to alterations in the GCDH gene generally detected by the Ambry Test: Glutaric Acidemia Type 1 except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: Glutaric Acidemia Type 1 can also give rise to clinical conditions similar or identical to Glutaric Acidemia Type 1. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request.