Primary hyperoxaluria type 2

Title

Other Names:

HP2; Oxalosis 2; Glyoxylate reductase/hydroxypyruvate reductase deficiency; HP2; Oxalosis 2; Glyoxylate reductase/hydroxypyruvate reductase deficiency; Glyceric aciduria; D-glycerate dehydrogenase deficiency See More

Categories:

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders; Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders; RDCRN See More

Summary Summary

Primary hyperoxaluria type 2 is a rare condition characterized by the overproduction of a substance called oxalate (also called oxalic acid). In the kidneys, the excess oxalate combines with calcium to form calcium oxalate, a hard compound that is the main component of kidney stones. Deposits of calcium oxalate can lead to kidney damage, kidney failure, and injury to other organs. Primary hyperoxaluria type 2 is caused by the shortage (deficiency) of an enzyme called glyoxylate reductase/hydroxypyruvate reductase (GRHPR) that normally prevents the buildup of oxalate. This enzyme shortage is caused by mutations in the GRHPR gene. Primary hyperoxaluria type 2 is inherited in an autosomal recessive pattern.^[1]

Last updated: 1/3/2013

Symptoms Symptoms

Primary hyperoxaluria type 2 is characterized by recurrent nephrolithiasis (deposition of calcium oxalate in the kidney and urinary tract), nephrocalcinosis (deposition of calcium oxalate in the kidney tissue), and end-stage renal disease (ESRD). After ESRD, oxalosis (widespread tissue deposition of calcium oxalate) usually develops. Presenting symptoms are typically those associated with the presence of kidney stones, including hematuria, renal colic (a type of abdominal pain caused by kidney stones), or obstruction of the urinary tract.^[2] The symptoms of primary hyperoxaluria type 2 are typically less severe than primary hyperoxaluria type 1 and may be limited to kidney stone formation. Symptom onset may occur in childhood or adolescence.^[2]^[3] End stage renal disease is rarely observed in childhood.^[3]

Last updated: 1/3/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Hyperoxaluria	High urine oxalate levels	0003159
Nephrocalcinosis	Too much calcium deposited in kidneys	0000121
Nephrolithiasis	Kidney stones	0000787
30%-79% of people have these symptoms
Recurrent urinary tract infections	Frequent urinary tract infections Urinary infection Urinary tract infection Urinary tract infections Urinary tract infections, recurrent [ more ]	0000010
Ureteral obstruction		0006000
5%-29% of people have these symptoms
Renal insufficiency	Renal failure Renal failure in adulthood [ more ]	0000083
Percent of people who have these symptoms is not available through HPO
Aminoaciduria	High urine amino acid levels Increased levels of animo acids in urine [ more ]	0003355
Autosomal recessive inheritance		0000007
Calcium oxalate nephrolithiasis		0008672
Hematuria	Blood in urine	0000790
Variable expressivity		0003828

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

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Cause Cause

Researchers have identified more than a dozen GRHPR mutations that cause this condition.^[2]^[4] These mutations either introduce signals that disrupt production of the glyoxylate reductase/hydroxypyruvate reductase enzyme or alter its structure. As a result, enzyme activity is absent or dramatically reduced. Glyoxylate builds up because of the enzyme shortage, and is converted to a compound called oxalate instead of glycolate. Oxalate, in turn, combines with calcium to form calcium oxalate, which the body cannot readily eliminate. Deposits of calcium oxalate can lead to the characteristic features of primary hyperoxaluria type 2.^[4]

Last updated: 1/3/2013

Inheritance Inheritance

Primary hyperoxaluria type 2 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.^[1]

Last updated: 1/3/2013

Treatment Treatment

The current management strategy includes high fluid intake, treatment with inhibitors of calcium oxalate crystallization, and temporary intensive dialysis for end-stage renal disease (ESRD) followed by kidney transplantation.^[2]^[3] Varying success has been reported following transplantation, with recurrence being a real possibility since hyperoxaluria and elevated L-glycerate levels persist.^[2]^[3]^[5] Careful management in the postoperative period, with attention to brisk urine output and use of calcium oxalate urinary inhibitors may help prevent complications.^[2]

To date, liver-kidney transplantation has not been used in primary hyperoxaluria type 2.^[2]^[3] This strategy may be considered, however, as there is more enzyme in the liver than in other tissues.^[2] More studies are needed before liver transplantation can be recommended.^[3] Other treatment modalities needing further investigation include liver cell transplantation and recombinant gene therapy to replace the missing enzyme.^[6]

Last updated: 1/3/2013

Prognosis Prognosis

While development of end-stage renal disease (ESRD) may be less common (and later occurring) in people with primary hyperoxaluria type 2 than in those with type 1, chronic and terminal renal insufficiency have been described.^[5]^[7] Prognosis depends on early treatment and management of hyperoxaluria and associated renal deterioration.^[6] Patients who develop ESRD and undergo kidney transplantation seem to carry a high risk of disease recurrence.^[3]^[5]

Last updated: 1/3/2013

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Other disorders that may present with a history of stone disease (and/or early stone formation) include primary hyperoxaluria type 1, primary hyperoxaluria type 3, Dent disease, primary renal tubular acidosis, cystinuria, xanthinuria, and adenine phosphoribosyltransferase deficiency (see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Primary hyperoxaluria type 2. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The International Registry for Hereditary Calcium Stone Diseases supports research for Primary hyperoxaluria type 2 by collecting information about patients with this diagnosis. You can join the registry to share your information with researchers and receive updates about participating in new research studies. Learn more about registries.
The The Primary Hyperoxaluria Registry supports research for Primary hyperoxaluria type 2 by collecting information about patients with this diagnosis. You can join the registry to share your information with researchers and receive updates about participating in new research studies. Learn more about registries.
The Rare Kidney Stone Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with primary hyperoxaluria, cystinuria, dihydroxyadeninuria, and Dent's disease through research. The Rare Kidney Stone Consortium has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Oxalosis and Hyperoxaluria Foundation (OHF)
201 East 19th Street
Suite 12E
New York, NY 10003
Toll-free: 1-800-OHF-8699
Fax: 212-777-0471
E-mail: info@ohf.org
Website: http://ohf.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Primary hyperoxaluria type 2. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Primary hyperoxaluria type 2. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My son was recently diagnosed with primary hyperoxaluria type 2. Is this something that he can eventually outgrow? Can his liver repair itself and begin producing the missing enzyme? If not, is there any chance of him leading a full life or will he develop end stage renal disease before he has a chance to get old and gray? See answer

Have a question? Contact a GARD Information Specialist.

References References

Primary hyperoxaluria. Genetics Home Reference (GHR). January 2008; http://ghr.nlm.nih.gov/condition/primary-hyperoxaluria. Accessed 1/2/2013.
Rumsby G. Primary Hyperoxaluria Type 2. GeneReviews. May 2011; http://www.ncbi.nlm.nih.gov/books/NBK2692/. Accessed 1/2/2013.
Leumann E, Hoppe B. The Primary Hyperoxalurias. JASN. September 1, 2001 ; http://jasn.asnjournals.org/content/12/9/1986.long. Accessed 1/2/2013.
GRHPR. Genetics Home Reference (GHR). January 2008; http://ghr.nlm.nih.gov/gene/GRHPR. Accessed 1/2/2013.
Hyperoxaluria, Primary, Type II. Online Mendelian Inheritance in Man (OMIM). November 2012; http://omim.org/entry/260000. Accessed 1/2/2013.
Shekarriz B, Stoller ML. Hyperoxaluria. Medscape Reference. March 2011; http://emedicine.medscape.com/article/444683-overview. Accessed 1/2/2013.
Marangella M, Petrarulo M, Cosseddu D. End-Stage Renal Failure in Primary Hyperoxaluria Type 2. N Engl J Med. 1994; http://www.nejm.org/doi/full/10.1056/NEJM199406093302318. Accessed 1/2/2013.