Test ID: HYOX
Hyperoxaluria Panel, Urine

Distinguishing between primary and secondary hyperoxaluria

Distinguishing between type 1 and type 2 primary hyperoxaluria

Distinguishing between primary and secondary hyperoxaluria.

• Informed Consent for Genetic Testing

Gas Chromatography-Mass Spectrometry (GC-MS)

Container/Tube: Plastic, 10-mL urine tube (Supply T068)

Specimen Volume: 10 mL

Collection Instructions:

1. Fasting-overnight (12-14 hours).

2. Have patient void the first-morning specimen, then collect specimen within 2 hours of first-morning void while patient continues to fast. Fluids are allowed.

3. No preservative.

4. Immediately freeze specimen.

Forms:

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.

Increased urinary oxalate frequently leads to renal stone formation and renal insufficiency. Identification to the cause of hyperoxaluria has important implications in therapy, management and prognosis.

Hyperoxalurias are classified as primary (genetically determined) and secondary. Type I (PH1), an autosomal recessive deficiency of peroxisomal alanine: glyoxylate aminotransferase due to mutations in the AGXT gene, is characterized by increased urinary oxalic, glyoxylic, and glycolic acids. PH1 manifestations include deposition of calcium oxalate in the kidneys (nephrolithiasis, nephrocalcinosis), and end-stage renal disease. Calcium oxalate deposits can be found in other tissues such as the heart and eyes, and lead to a variety of additional symptoms. Age of onset is variable with a small percentage of patients presenting in the first year of life with failure to thrive, nephrocalcinosis, and metabolic acidosis. Approximately half of affected individuals show manifestations of PH1 in late childhood or early adolescence, and the remainder present in adulthood with recurrent renal stones. Some PH1 individuals respond to supplementary pyridoxine therapy.

Hyperoxaluria type II (PH 2) is due to a defect in GRHPR gene resulting in a deficiency of the enzyme hydroxypyruvate reductase. PH2 is autosomal recessive and identified by an increase in urinary oxalic and glyceric acids. Like PH1, PH2 is characterized by deposition of calcium oxalate in the kidneys (nephrolithiasis, nephrocalcinosis), and end-stage renal disease. Most individuals have symptoms of PH2 during childhood, and it is thought that PH2 is less common than PH1.

Secondary hyperoxalurias are due to hyperabsorption of oxalate (enteric hyperoxaluria); total parenteral nutrition in premature infants; ingestion of oxalate, ascorbic acid, or ethylene glycol; or pyridoxine deficiency, and may respond to appropriate therapy.

A diagnostic workup in an individual with hyperoxaluria demonstrates increased concentration of oxalate in urinary metabolite screening. If either glycolate or glycerate is present, a primary hyperoxaluria is indicated. Additional analyses can include molecular testing for PH1 or PH2.

GLYCOLATE

0-31 days: 0-57 mg/g creatinine

1-5 months: 0-54 mg/g creatinine

6-12 months: 0-60 mg/g creatinine

1-5 years: 0-89 mg/g creatinine

> or =6 years: 0-78 mg/g creatinine

GLYCERATE

0-31 days: 0-38 mg/g creatinine

1-5 months: 0-71 mg/g creatinine

6-12 months: 0-56 mg/g creatinine

1-5 years: 0-17 mg/g creatinine

> or =6 years: 0-8 mg/g creatinine

OXALATE

0-31 days: 0-301 mg/g creatinine

1-5 months: 0-398 mg/g creatinine

6-12 months: 0-280 mg/g creatinine

1-5 years: 0-128 mg/g creatinine

6-10 years: 0-72 mg/g creatinine

> or =11 years: 0-56 mg/g creatinine

GLYOXYLATE

0-31 days: 0.0-7.9 mg/g creatinine

1-5 months: 0.0-11.4 mg/g creatinine

6-12 months: 0.0-5.5 mg/g creatinine

1-5 years: 0.0-3.9 mg/g creatinine

> or =6 years: 0.0-2.9 mg/g creatinine

Increased concentrations of oxalate and glycolate indicate type 1 hyperoxaluria.

Increased concentrations of oxalate and glycerate indicate type 2 hyperoxaluria.

Increased concentrations of oxalate with normal concentrations of glycolate and glycerate indicate secondary hyperoxaluria.

Ascorbic acid will falsely elevate oxalic acid results.

1. Monico CG, Persson M, Ford GC, et al: Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II. Kidney Int 2002;62:392-400

2. Danpure CJ: Primary hyperoxaluria. In The Metabolic Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 3323-3367

3. Byrd DJ, Latta K: Hyperoxaluria. In Physician's Guide to the Laboratory Diagnosis of Metabolic Disease. Edited by N Blau, ED Chapman. Hall Medical, 1996, pp 377-390

4. Fraser AD: Importance of glycolic acid analysis in ethylene glycol poisoning. Clin Chem 1998;44(8):1769

Urine corresponding to 0.25 mg creatinine is aliquoted. Oxidation of 2-keto acids is performed by reaction with hydroxylamine hydrate. The urine is acidified and extracted with ethyl acetate. After evaporation, the dry residue is sialylated with N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA)/1% trimethylchlorosilane (TMCS) and analyzed by capillary gas chromatography/mass spectrometry (GC/MS) for glycolate, glycerate, glyoxylate, and oxalate in single ion monitoring mode. Quantitation is performed against a known concentration of a stable isotope of each compound.(Mamer OA, Osei-Twum EY, Reimer MLJ, et al: Determination of oxalic, glycolic, glyoxylic, glyceric and hydroxypyruvic acids in a single GC/MS analysis useful for distinguishing hyperoxaluria types I and II. In Advances in Chemical Diagnosis and Treatment of Metabolic Disorders. Vol.2. Edited by I Matsumoto, T Kuhara, OA Mamer, et al. Kanazawa Medical Publishers, Limited 1994, pp 87-95)

Varies; Batched 1 time per month; 8 a.m.

82544