Alanine:Glyoxylate Aminotransferase (AGXT) Mutation Analysis (G170R), Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 clinical signs, increased urinary oxalate, glycolate, and glycerate excretion are present. Diagnostic confirmation requires the enzyme assay of the liver tissue, although this test is not readily available.
The toxicity of excess oxalate has been implicated in disease pathogenesis. Thus, treatment options have primarily centered on limiting oxalate ingestion and absorption. Pyridoxine (vitamin B6) has proven to be a promising therapeutic agent by increasing the concentration of cofactor involved in the metabolic reactions that decrease oxalate production. However, only 20% to 30% of patients have been known to be responsive to pyridoxine. Testing patients for pyridoxine responsiveness has been recommended at any stage of renal function, although assessment of pyridoxine responsiveness is not always easy to perform and diagnostic criteria have not been standardized. Recently, researchers at Mayo Clinic found that patients with a particular mutation (Gly170Arg) in the AGXT gene are responsive to the pyridoxine, while affected individuals without this mutation are not responsive.
Identifying patients with the pyridoxine responsive form of PH1
Determining the presence of the Gly170Arg (G170R) mutation in the AGXT gene
Carrier testing of at-risk family members
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 available clinical information.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause PH1. Therefore, the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Many disorders may present with symptoms similar to those associated with PH1. PH2, another type of primary hyperoxaluria, is not detected by this assay. Therefore, biochemical testing (HYOX / Hyperoxaluria Panel, Urine) is recommended prior to DNA analysis to distinguish between these two disorders.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Milosevic D, Rinat C, Batinic D, Frishberg Y: Genetic analysis-a diagnostic tool for primary hyperoxaluria type I. Pediatr Nephrol 2002 Nov;17(11):896-898
2. Pirulli D, Marangella M, Amoroso A: Primary hyperoxaluria: genotype-phenotype correlation. J Nephrol 2003 Mar-Apr;16(2):297-309
3. Amoroso A, Pirulli D, Florian F, et al: AGXT gene mutations and their influence on clinical heterogeneity of type I primary hyperoxaluria. J Am Soc Nephrol 2001 Oct;12(10):2072-2079