Sorted By Test Name - Mayo Medical Laboratories

AGXKM
89916
helpful in supporting the diagnosis in patients with reduced kidney function, with values >50 micromol/L
highly suggestive of PH1 when GFR is A), and p.Ile244Thr (c.731T->C). These mutations account for at least 1 of the 2 affected
alleles in approximately 70% of individuals with PH1. Direct sequencing of the AGXT gene is predicted
to identify 99% of alleles in individuals who are known by enzyme analysis to be affected with PH1.
While age of onset and severity of disease is variable and not necessarily predictable by genotype, a
correlation between pyridoxine responsiveness and homozygosity for the p.Gly170Arg mutation has been
observed. (Note: testing for the p.Gly170Arg mutation only is available by ordering AGXT/83643
Alanine:Glyoxylate Aminotransferase [AGXT] Mutation Analysis [G170R], Blood). Pyridoxine (vitamin
B6) is a known cofactor of AGT and is effective in reducing urine oxalate excretion in some PH1 patients
treated with pharmacologic doses. Individuals with 2 copies of the p.Gly170Arg mutation have been
shown to normalize their urine oxalate when treated with pharmacologic doses of pyridoxine and those
with a single copy of the mutation show reduction in urine oxalate. This is valuable because not all
patients have been shown to be responsive to pyridoxine, and strategies that help to identify the
individuals most likely to benefit from such targeted therapies are desirable.
Useful For: Confirming a diagnosis of primary hyperoxaluria type 1 Carrier testing for individuals
with a family history of primary hyperoxaluria type 1 in the absence of known mutations in the family
Interpretation: An interpretative report will indicate if results are diagnostic for primary hyperoxaluria
type 1 (2 mutations identified), if the patient is a carrier for primary hyperoxaluria type 1 (1 mutation
identified), or if no mutations are identified.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Milliner DS: The primary hyperoxalurias: an algorithm for diagnosis. Am J
Nephrol 2005;25(2):154-160 2. Monico CG, Rossetti S, Olson JB, Milliner DS: Pyridoxine effect in type
I primary hyperoxaluria is associated with the most common mutant allele. Kidney Int
2005;67(5):1704-1709 3. Monico CG, Rossetti S, Schwanz HA, et al: Comprehensive mutation screening
in 55 probands with type 1 primary hyperoxaluria shows feasibility of a gene-based diagnosis. J Am Soc
Nephrol 2007;18:1905-1914 4. Rumsby G, Williams E, Coulter-Mackie M: Evaluation of mutation
screening as a first line test for the diagnosis of the primary hyperoxalurias. Kidney Int
2004;66(3):959-963 5. Williams EL, Acquaviva C, Amoroso, A, et al: Primary hyperoxaluria type I:
update and additional mutation analysis of the AGXT gene. Hum Mutat 2009;30:910-917 6. Williams E,
Rumsby G: Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of
patients with primary hyperoxaluria type 1. Clin Chem 2007;53(7):1216-1221 7. Communique April
2007: Laboratory and Molecular Diagnosis of Primary Hyperoxaluria and Oxalosis
AGXT Gene, Known Mutation
Clinical Information: Primary hyperoxaluria type 1 (PH1) is a hereditary disorder of glyoxylate
metabolism caused by deficiency of alanine:glyoxylate-aminotransferase (AGT), a hepatic enzyme that
converts glyoxylate to glycine. Absence of AGT activity results in conversion of glyoxylate to oxalate,
which is not capable of being degraded. Therefore, excess oxalate is excreted in the urine, causing kidney
stones (urolithiasis), nephrocalcinosis, and kidney failure. As kidney function declines, blood levels of
oxalate increase markedly, and oxalate combines with calcium to form calcium oxalate deposits in the
kidney, eyes, heart, bones, and other organs, resulting in systemic disease. Pyridoxine (vitamin B6), a
cofactor of AGT, is effective in reducing urine oxalate excretion in some PH1 patients. Presenting
symptoms of PH1 include nephrolithiasis, nephrocalcinosis, or end-stage kidney disease with or without a
history of urolithiasis. Age of symptom onset is variable; however, most individuals present in childhood
or adolescence with symptoms related to kidney stones. In some infants with a more severe phenotype,
kidney failure may be the initial presenting feature. Less frequently, affected individuals present in
adulthood with recurrent kidney stones or kidney failure. End-stage kidney failure is most often seen in
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