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Disease Profile

Primary hyperoxaluria type 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

E74.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

HP2; Oxalosis 2; Glyoxylate reductase/hydroxypyruvate reductase deficiency;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders;

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]

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]

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.

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
Repeated bladder infections
Repeated urinary tract infections
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

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]

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]

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

    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.

        References

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

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