Sorted By Test Name - Mayo Medical Laboratories

the third decade of life, but can occur at any age. The exact prevalence and incidence of PH1 are not
known, but prevalence rates of 1 to 3 per million population and incidences of 0.1 per million/year have
been estimated from population surveys. Biochemical testing is indicated in patients with possible
primary hyperoxaluria, and can be performed prior to molecular testing. Measurement of urinary oxalate
in a timed, 24-hour urine collection is strongly preferred, with correction to adult body surface area in
pediatric patients (HYOX/86213 Hyperoxaluria Panel, Urine; OXU/8669 Oxalate, Urine). In very young
children (incapable of performing a timed collection), random urine oxalate to creatinine ratios may be
used to determine oxalate excretion. In patients with reduced kidney function, POXA/81408 Oxalate,
Plasma is also recommended. Urinary excretion of oxalate of >1.0 mmol/1.73 m(2)/24 hours is strongly
suggestive of, but not diagnostic for, this disorder, as there are other forms of inherited (type 2 and
non-PH1/PH2) hyperoxaluria and secondary hyperoxaluria that may result in similarly elevated urine
oxalate excretion rates. An elevated urine glycolate in the presence of hyperoxaluria is suggestive of PH1.
Caution is warranted in interpretation of urine oxalate excretion in patients with reduced kidney function
as urine oxalate concentrations may be lower due to reduced glomerular filtration rate (GFR). The plasma
oxalate concentration may also be 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: molecular testing is available as AGXMS/89915
AGXT Gene, Full Gene Analysis and, for the p.Gly170Arg mutation only, as 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. Site-specific (known
mutation) testing for mutations that have already been identified in an affected patient is useful for
confirming a suspected diagnosis in a family member. It is also useful for determining whether at-risk
individuals are carriers of the disease and, subsequently, at risk for having a child with PH1 deficiency.
Useful For: Carrier testing of individuals with a family history of primary hyperoxaluria type 1
Diagnostic confirmation of primary hyperoxaluria type 1 deficiency when familial mutations have been
previously identified Prenatal testing when 2 familial mutations have been previously identified in an
affected family member
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,
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 64