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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Hyperoxaluria	Very frequent (present in 80%-99% of cases)
Nephrocalcinosis	Very frequent (present in 80%-99% of cases)
Nephrolithiasis	Very frequent (present in 80%-99% of cases)
Recurrent urinary tract infections	Frequent (present in 30%-79% of cases)
Ureteral obstruction	Frequent (present in 30%-79% of cases)
Renal insufficiency	Occasional (present in 5%-29% of cases)
Aminoaciduria	-
Autosomal recessive inheritance	-
Calcium oxalate nephrolithiasis	-
Hematuria	-
Variable expressivity	-

Last updated: 8/1/2017

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

Management Guidelines

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.

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

Do you have updated information on this condition? Let us know.

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 studying or have studied 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

International Registry for Hereditary Calcium Stone Diseases
Study Coordinator: Julie Olson
Mayo Clinic
200 First Street SW
Eisenberg SL-33
Rochester MN 55905
Phone: 800-270-4637 (toll-free)
Fax: 507-255-0770
Email: hyperoxaluriacenter@mayo.edu, rarekidneystones@mayo.edu
The Primary Hyperoxaluria Registry is a patient database where information is brought together, analyzed and used to advance understanding of hyperoxaluria. The Registry has the ability to track a patient’s health over a period of years and decades to help accurately answer questions patients have about the disease.
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
http://www.ohf.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Ninth International Primary Hyperoxaluria Workshop Saturday, August 28, 2010 - Sunday, August 29, 2010
Location: New York, NY
Description: The goals of this workshop were to (1) bring together the multidisciplinary primary hyperoxaluria (PH) treatment and research communities for dialogue and interaction in order to better understand the etiology of the PHs, optimize diagnosis and treatment strategies, and identify novel research and treatment approaches; (2) foster new collaborations among U.S. and international researchers and clinicians from a variety of backgrounds; (3) encourage the entry of new and junior researchers into the field of research on PHs and other oxalate-related diseases; and (4) inform PH patients, families, and friends of the latest advances in the understanding and clinical management of PHs.

Contact: Rebekah S. Rasooly, Ph.D.(301) 594-6007rrl85i@nih.gov

Co-funding Institute(s): National Institute of Diabetes and Digestive and Kidney Diseases, Office of Rare Diseases Research
- Agenda ( - 28KB)
- Participants ( - 64KB)
- Summary ( - 43KB)

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.