Glutaric Acidemia, Type 1 - GCDH Sequencing
Glutaric acidemia, type 1 (GA1) is an inborn error of
lysine, hydroxylysine and tryptophan metabolism caused by the deficiency of
glutaryl-CoA dehydrogenase (GCDH). Patients are often identified via newborn
screening. However, some patients are “low excretors” and can exhibit normal
or mildly elevated biochemical analytes making a definitive diagnosis of GA1
difficult without molecular analysis.
GA1 is a neurodegenerative disorder with loss of neurons in
the basal ganglia. Clinical features vary, but often include macrocephaly, gait
abnormalities, hypotonia, spasms, rigidity and seizures. Retinal or subdural
hemorrhages can also occur. Other than possible macrocephaly, patients appear
normal at birth. Clinical features are typically preceded by an acute
encephalopathic illness with fever before five years of age.
GCDH sequencing will detect mutations in approximately 95% of
individuals with GA1 and is available from the Metabolic Laboratory of the
Greenwood Genetic Center. Molecular testing is useful to confirm the diagnosis
and to identify the disease causing mutations within a family to allow for
carrier testing and prenatal diagnosis.
Specimen requirements: 5 to 10 ml of peripheral blood
collected in an EDTA (lavendar top) Vacutainer tube is preferred. The minimal
blood needed for reliable DNA isolation is 3 ml. If necessary, ACD solution A
Vacutainer tubes (yellow top) may be submitted. Please contact the laboratory
for more information.
Transport: Please contact Tim Wood or the molecular
diagnostic lab coordinator (1-800-473-9411) for shipping information. The
specimen should be kept at room temperature and delivered via overnight
shipping. FedEx is preferred. If shipment is delayed by one or two days, the
specimen should be refrigerated and shipped at room temperature. Do not
freeze the specimen. Samples collected on Friday can be safely designated
for Monday delivery.
Analysis standards: Analysis will be complete within 4
weeks of sample receipt. The lab director assesses the quality and
interpretation of results. Technical staff members independently assess the
quality and interpretation of the test. The Greenwood Genetic Center Metabolic
Diagnostic Laboratory is CLIA certified and actively participates in CAP
proficiency surveys.
Reporting of Test Results: Test results with
interpretation will be mailed and/or faxed following completion of the test.
Verbal reports will be telephoned to the person(s) requesting the test when an
abnormal test result occurs. Consultation with the laboratory director and
explanations of testing protocols will be supplied upon request.
CPT Codes: 83890, 83898 (x4), 83904 (x5), 83909 (x5),
83912
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