Alanine:Glyoxylate Aminotransferase (AGXT) Mutation Analysis (G170R), Blood

CPT CODE:

USEFUL FOR:

Identifying patients with the pyridoxine responsive form of PH1
Determining the presence of the Gly170Arg (G170R) mutationin the AGXT gene
Carrier testing of at-risk family members

SPECIMEN REQUIRED:

"Molecular Genetics - Congenital Inherited Diseases Patient Information Sheet" (Supply T521 or seeSpecial Instructions) is required for all orders. If notordering electronically, please submit the above informationsheet along with a "Molecular Genetics Request Form"(Supply T245) with the specimen. An "Informed Consent forDNA Testing" (Supply T576) is available. See Special Instructions for a copy of the form.
Specimen must arrive within 96 hours of draw. Draw blood in a lavender-top (EDTA) tube or a yellow-top (ACD) tube, and send 2 mL of EDTA or ACD whole blood in original VACUTAINER. Invert several times to mix blood. Forward unprocessed whole blood promptly at ambienttemperature.

TRANSPORT TEMPERATURE:

Ambient\Refrig OK\Frozen NO

CLINICAL INFORMATION:

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease ranging from renal failure in infancy to mere renal stones in late adulthood. It is caused by deficiencies of the liver-specific peroxisomal enzyme AGXT (alanine-glyoxylate amino-transferase). The diagnosis may be suspected when clinicalsigns, increased urinary oxalate, glycolate, and glycerateexcretion are present. Diagnostic confirmation requires theenzyme assay of the liver tissue, although this test is not readilyavailable.
The toxicity of excess oxalate has been implicated in disease pathogenesis. Thus, treatment options have primarily centeredon limiting oxalate ingestion and absorption. Pyridoxine (vitaminB[6]) has proven to be a promising therapeutic agent byincreasing the concentration of cofactor involved in the metabolicreactions that decrease oxalate production. However, only20% to 30% of patients have been known to be responsive topyridoxine. Testing patients for pyridoxine responsiveness hasbeen recommended at any stage of renal function, althoughassessment of pyridoxine responsiveness is not always easy toperform and diagnostic criteria have not been standardized.Recently, researchers at Mayo Clinic found that patients with aparticular mutation (Gly170Arg) in the AGXT gene are responsiveto the pyridoxine, while affected individuals without this mutationare not responsive.

CLINICAL INTERPRETATION:

Reported as negative or positive. The laboratory provides an interpretation of the results. This interpretation includes an overview of the results and their significance and a correlation to availableclinical information.

REFERENCE VALUES:

An interpretive report will be provided.