Rare Gastroenterology News

Disease Profile

Primary hyperoxaluria type 1

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.

Unknown

Age of onset

All ages

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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)

HP1; Oxalosis 1; Glycolic aciduria;

Categories

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

Summary

Primary hyperoxaluria type 1 (PH1) is a rare disorder that mainly affects the kidneys. It results from buildup of a substance called oxalate, which normally is filtered through the kidneys and excreted in the urine. In people with PH1, the accumulated oxalate is deposited in the kidneys and urinary tract. It combines with calcium, forming the main component of kidney and bladder stones (calcium oxalate).[1][2]

Signs and symptoms of PH1 vary in severity and may begin any time from infancy to early adulthood. Symptoms may include recurrent kidney stones; blood in the urine; and urinary tract infections. Left untreated, PH1 can result in end-stage renal disease, which is life-threatening.[1][2]

PH1 is due to mutations in a gene called AGXT. Inheritance is autosomal recessive.[1]

Early treatment is important for maintaining kidney function. Each person's treatment plan depends on his/her symptoms and the severity of the condition. Management may involve high fluid intake; vitamin B6 (pyridoxine); calcium-oxalate crystallization inhibitors (citrate, pyrophosphate, and magnesium); kidney stone therapies; and dialysis in some cases. Liver and/or kidney transplantation may be needed.[3]

Symptoms

The symptoms and severity of primary hyperoxaluria type 1 (PH1) can vary. The age that symptoms begin ranges from birth to the sixth decade of life (although there are exceptions). About 19% of people with PH1 have a severe, very early-onset form that becomes apparent within a few months after birth. At the milder end of the spectrum, some people with PH1 go without any symptoms for over 40 or 50 years. The median age of onset is about 5-6 years.

Features of renal involvement can range from nephrocalcinosis and renal failure in infancy, to only occasional stones diagnosed in adulthood.[2] Kidney stones are commonly the first sign of hyperoxaluria. Symptoms of kidney stones can include sudden abdominal or flank pain; blood in the urine; frequent urge to urinate; pain while urinating; or fever and chills.[4]

Untreated PH1 leads to kidney failure, which is life-threatening. Symptoms of kidney failure can include decreased or no urine output; feeling ill or tired; loss of appetite; nausea and vomiting; and pale skin due to anemia.[4]

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
Abnormality of circulating enzyme level
0011021
Anemia
Low number of red blood cells or hemoglobin
0001903
Calcinosis
Calcium buildup in soft tissues of body
0003761
Hyperoxaluria
High urine oxalate levels
0003159
Metabolic acidosis
0001942
Nephrocalcinosis
Too much calcium deposited in kidneys
0000121
Nephrolithiasis
Kidney stones
0000787
30%-79% of people have these symptoms
Decreased glomerular filtration rate
0012213
Dysuria
Painful or difficult urination
0100518
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hematuria
Blood in urine
0000790
5%-29% of people have these symptoms
Abnormality of the skeletal system
Skeletal abnormalities
Skeletal anomalies

[ more ]

0000924
Enuresis
0000805
Recurrent urinary tract infections
Frequent urinary tract infections
Repeated bladder infections
Repeated urinary tract infections
Urinary tract infections
Urinary tract infections, recurrent

[ more ]

0000010
Stage 5 chronic kidney disease
0003774
1%-4% of people have these symptoms
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality

[ more ]

0000164
Atherosclerosis
Narrowing and hardening of arteries
0002621
Stroke
0001297
Percent of people who have these symptoms is not available through HPO
Acrocyanosis
Persistent blue color of hands, feet, or parts of face
0001063
Arterial occlusion
0025324
Atrioventricular block
Interruption of electrical communication between upper and lower chambers of heart
0001678
Autosomal recessive inheritance
0000007
Bone pain
0002653
Calcinosis cutis
0025520
Calcium oxalate nephrolithiasis
0008672
Choroidal neovascularization
0011506
Cutis marmorata
0000965
Gangrene
Death of body tissue due to lack of blood flow or infection
0100758
Increased bone mineral density
Increased bone density
0011001
Intermittent claudication
0004417
Optic atrophy
0000648
Optic neuropathy
Damaged optic nerve
0001138
Pathologic fracture
Spontaneous fracture
0002756
Peripheral arterial stenosis
0004950
Peripheral neuropathy
0009830
Raynaud phenomenon
0030880
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Retinal crystals
0030507
Retinopathy
Noninflammatory retina disease
0000488

Cause

Primary hyperoxaluria type 1 is caused by mutations in a gene called AGXT. This gene gives the body instructions for making an enzyme called alanine-glyoxylate aminotransferase. This enzyme is found in cell structures called peroxisomes in liver cells. It converts a compound called glyoxylate to the amino acid glycine.

Mutations in the AGXT gene lead to a decrease in the amount or function of the enzyme, preventing the breakdown of glyoxylate. This is turn causes glyoxylate to accumulate, and it is converted to oxalate instead of glycine. Excess oxalate that is not excreted from the body then combines with calcium to form calcium oxalate, which damages the kidneys and other organs.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The goal of treatment for primary hyperoxaluria type 1 (PH1) is to minimize calcium oxalate deposition and maintain renal function. Early diagnosis and prompt therapy is critical to preserve the function of the kidneys for as long as possible.

    General therapies for preventing kidney stones benefit all people with PH1. Recommendations for this include:

    • drinking large amounts of fluid
    • oral potassium citrate to inhibit calcium oxalate crystallization
    • drugs such as thiazides to decrease calcium in the urine
    • avoiding significant intake of vitamin C or D (they promote stone formation)
    • supplementation of dietary calcium

    Treatment for kidney stones may involve shock wave lithotripsypercutaneous nephrolithotomy, and/or ureteroscopy.

    Reducing the body's production of oxalate involves treatment with pyridoxine. While only about 10%-30% of people with PH1 respond to treatment with pyridoxine, it has been recommended that all people with PH1 receive a minimum 3-month trial at the time of initial diagnosis.

    Dialysis to remove oxalate in people with PH1 has limitations, but may be indicated in specific circumstances in some people with PH1.

    Lastly, organ transplantation is an option for therapy. There has been much discussion among experts regarding the best transplantation strategy for people with PH1. Depending on each person's response to other therapies and the disease severity, options may include combined liver-kidney transplant; sequential liver-kidney transplant; an isolated kidney transplant, or an isolated liver transplant.[2]

    Other therapies for PH1 are under investigation and may become options for people with PH1 in the future.

    People with questions about the treatment of PH1 for themselves or family members should speak with their doctor for treatment options and advice.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    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

      Organizations Providing General Support

        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 1. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
        • The Oxalosis and Hyperoxaluria Foundation (OHF), the leading organization dedicated to the awareness, understanding and treatment of primary hyperoxaluria, provides information about this condition.

          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.
          • 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 1. Click on the link to view a sample search on this topic.

            References

            1. Primary hyperoxaluria. Genetics Home Reference. December, 2015; https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria.
            2. Marion B Coulter-Mackie, Colin T White, Dirk Lange, and Ben H Chew. Primary Hyperoxaluria Type 1. GeneReviews. July 17, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1283/.
            3. Pierre Cochat. Primary hyperoxaluria type 1. Orphanet. June, 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=93598.
            4. Symptoms. Oxalosis & Hyperoxaluria Foundation. 2015; https://ohf.org/symptoms/.
            5. Primary Hyperoxaluria. NORD. 2014; https://rarediseases.org/rare-diseases/primary-hyperoxaluria.
            6. Pierre Cochat et. al. Primary Hyperoxaluria Type 1. Nephrology Dialysis Transplantation. 2012; 27(5):1729-1736. https://www.medscape.com/viewarticle/764202_5.
            7. Lorenz EC, Michet CJ, Milliner DS & Lieske JC. Update on oxalate crystal disease. Curr Rheumatol Rep. 2013 Jul;.. July, 2013; 15(7):340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710657/.

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