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Genetics Home Reference: your guide to understanding genetic conditions
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Primary hyperoxaluria

Reviewed December 2015

What is primary hyperoxaluria?

Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.

Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.

There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear.

How common is primary hyperoxaluria?

Primary hyperoxaluria is estimated to affect 1 in 58,000 individuals worldwide. Type 1 is the most common form, accounting for approximately 80 percent of cases. Types 2 and 3 each account for about 10 percent of cases.

What genes are related to primary hyperoxaluria?

Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. These genes provide instructions for making enzymes that are involved in the breakdown and processing of protein building blocks (amino acids) and other compounds. The enzyme produced from the HOGA1 gene is involved in the breakdown of an amino acid, which results in the formation of a compound called glyoxylate. This compound is further broken down by the enzymes produced from the AGXT and GRHPR genes.

Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs.

Related Gene(s)

Changes in these genes are associated with primary hyperoxaluria.

  • AGXT
  • GRHPR
  • HOGA1

How do people inherit primary hyperoxaluria?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of primary hyperoxaluria?

These resources address the diagnosis or management of primary hyperoxaluria and may include treatment providers.

  • Gene Review: Primary Hyperoxaluria Type 1 (http://www.ncbi.nlm.nih.gov/books/NBK1283)
  • Gene Review: Primary Hyperoxaluria Type 2 (http://www.ncbi.nlm.nih.gov/books/NBK2692)
  • Gene Review: Primary Hyperoxaluria Type 3 (http://www.ncbi.nlm.nih.gov/books/NBK316514)
  • Genetic Testing Registry: Hyperoxaluria (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0020500)
  • Genetic Testing Registry: Primary hyperoxaluria (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0020501)

You might also find information on the diagnosis or management of primary hyperoxaluria in Educational resources and Patient support.

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about primary hyperoxaluria?

You may find the following resources about primary hyperoxaluria helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for primary hyperoxaluria?

  • congenital oxaluria
  • D-glycerate dehydrogenase deficiency
  • glyceric aciduria
  • glycolic aciduria
  • hepatic AGT deficiency
  • hyperoxaluria, primary
  • oxalosis
  • oxaluria, primary
  • peroxisomal alanine:glyoxylate aminotransferase deficiency
  • primary oxalosis
  • primary oxaluria

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about primary hyperoxaluria?

Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding primary hyperoxaluria?

acids ; aciduria ; alanine ; amino acid ; autosomal ; autosomal recessive ; breakdown ; calcium ; cell ; compound ; congenital ; deficiency ; dehydrogenase ; enzyme ; ESRD ; excrete ; excretion ; gene ; hematuria ; hepatic ; inherited ; injury ; kidney ; kidney stones ; protein ; recessive ; renal ; renal disease ; stage

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Allard L, Cochat P, Leclerc AL, Cachat F, Fichtner C, De Souza VC, Garcia CD, Camoin-Schweitzer MC, Macher MA, Acquaviva-Bourdain C, Bacchetta J. Renal function can be impaired in children with primary hyperoxaluria type 3. Pediatr Nephrol. 2015 Oct;30(10):1807-13. doi: 10.1007/s00467-015-3090-x. Epub 2015 May 14. (http://www.ncbi.nlm.nih.gov/pubmed/25972204?dopt=Abstract)
  • Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013 Aug 15;369(7):649-58. doi: 10.1056/NEJMra1301564. Review. Erratum in: N Engl J Med. 2013 Nov 28;369(22):2168. (http://www.ncbi.nlm.nih.gov/pubmed/23944302?dopt=Abstract)
  • Gene Review: Primary Hyperoxaluria Type 1 (http://www.ncbi.nlm.nih.gov/books/NBK1283)
  • Gene Review: Primary Hyperoxaluria Type 2 (http://www.ncbi.nlm.nih.gov/books/NBK2692)
  • Gene Review: Primary Hyperoxaluria Type 3 (http://www.ncbi.nlm.nih.gov/books/NBK316514)
  • Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012 Jun 12;8(8):467-75. doi: 10.1038/nrneph.2012.113. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22688746?dopt=Abstract)
  • Hopp K, Cogal AG, Bergstralh EJ, Seide BM, Olson JB, Meek AM, Lieske JC, Milliner DS, Harris PC; Rare Kidney Stone Consortium. Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria. J Am Soc Nephrol. 2015 Oct;26(10):2559-70. doi: 10.1681/ASN.2014070698. Epub 2015 Feb 2. (http://www.ncbi.nlm.nih.gov/pubmed/25644115?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2015
Published: February 8, 2016