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Test ID: HYOX    
Hyperoxaluria Panel, Urine

Useful For Suggests clinical disorders or settings where the test may be helpful

Distinguishing between primary and secondary hyperoxaluria

 

Distinguishing between primary hyperoxaluria types 1, 2, and 3

Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request

Distinguishing among primary hyperoxaluria types 1, 2, and 3, and secondary hyperoxaluria.

Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.

See Hyperoxaluria Diagnostic Algorithm in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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

 

Hyperoxalurias are classified as primary and secondary. Primary hyperoxaluria is an inherited disorder of oxalate metabolism while secondary hyperoxaluria is an acquired condition resulting from either increased intake of dietary oxalate or altered intestinal oxalate absorption. Primary hyperoxalurias are classified into types 1, 2, and 3.

 

Type 1 (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 is the most common with manifestations that include deposition of calcium oxalate in the kidneys (nephrolithiasis, nephrocalcinosis), and end-stage renal disease. Calcium oxalate deposits can be further deposited 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 individuals with PH1 respond to supplementary pyridoxine therapy.

 

Hyperoxaluria type 2 (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.

 

Hyperoxaluria type 3 (PH3), due to recessive mutations in HOGA1 (formerly DHDPSL), occurs in a small percentage of individuals with primary hyperoxaluria. HOGA1 encodes a mitochondrial 4-hydroxy-2-oxoglutarate aldolase that catalyzes the 4th step in the hydroxyproline pathway. PH3 is characterized biochemically by increased urinary excretion of oxalate and 4-hydroxy-2-oxoglutarate (HOG). As with PH types 1 and 2, PH type 3 is characterized by calcium-oxalate deposition in the kidneys and/or kidney stone formation. Most individuals with PH3 have early onset disease with recurrent kidney stones and urinary tract infections as common symptoms. End-stage renal disease is not a characteristic of PH3. Of note, individuals with heterozygous mutations in HOGA1 can have variable and intermittent elevations of urine oxalate.

 

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 glycolate, glycerate, or HOG is present, a primary hyperoxaluria is indicated. Additional analyses can include molecular testing for PH1 (AGXTG / Alanine:Glyoxylate Aminotransferase (AGXT) Mutation Analysis (G170R), Blood or AGXTZ / AGXT Gene, Full Gene Analysis), PH2 (GRHPZ / GRHPR Gene, Full Gene Analysis), or PH3 (HOGA1 testing not available at Mayo at  this time).

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.

 

Age Groups (mg/g creatinine)

0-1 month

2-6 months

7-12 months

13 months-6 years

7-10 years

>10 years

Glycolate

0-60

0-75

0-75

0-75

0-75

0-50

Glycerate

0-75

0-125

0-125

0-55

0-55

0-25

Oxalate

0-400

0-400

0-300

0-150

0-100

0-75

4-Hydroxy-2-Oxoglutarate (HOG)

0-15

0-10

0-5

0-5

0-5

0-5

Interpretation Provides information to assist in interpretation of the test results

Increased concentrations of oxalate and glycolate indicate type 1 hyperoxaluria.

 

Increased concentrations of oxalate and glycerate indicate type 2 hyperoxaluria.

 

Increased concentrations of oxalate and 4-hydroxy-2-oxoglutarate indicate type 3 hyperoxaluria.

 

Increased concentrations of oxalate with normal concentrations of glycolate, glycerate, and 4-hydroxy-2-oxoglutarate indicate secondary hyperoxaluria.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Ascorbic acid will falsely elevate oxalic acid results.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Bhasin B, Urekli HM, Atta MG: Primary and secondary hyperoxaluria: Understanding the enigma. World J Nephrol 2015;4(2):235-244 DOI:10.5527/wjn.v4.i2.235

2. Danpure CJ: Primary Hyperoxaluria. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York. McGraw-Hill, 2014. Accessed August 26 2015. Available at: http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62641527

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

5. Beck BB, Baasner A, Buescher A, et al: Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies. Eur J Hum Genet 2013;21:162-172

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test


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