Rare Nephrology News

Disease Profile

Adenine phosphoribosyltransferase deficiency

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

E79.8

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)

2,8-dihydroxyadenine urolithiasis; APRT deficiency

Categories

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

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 976

Definition
A rare genetic nephropathy secondary to a disorder of purine metabolism characterized by the formation and hyperexcretion of 2,8-dihydroxyadenine (2,8-DHA) in urine, causing urolithiasis and crystalline nephropathy.

Epidemiology
Prevalence is estimated at 1/50,000 to 1/100,000 in Caucasian, 1/27,000 in Japanese and > 1/15,000 in Icelandic populations. Adenine phosphoribosyltransferase deficiency (APRT) deficiency appears to equally affect children and adults, male or female. In Caucasian populations, heterozygous prevalence is estimated between 0.4% and 1.2%.

Clinical description
Clinical manifestations include symptoms usually associated with urolithiasis. Stones are typically radiolucent. Onset can be between infancy and the 4th decade of life, or sometimes even later. A small portion of patients remain asymptomatic. The disease can present not only as urolithiasis but also as crystalline nephropathy secondary to the precipitation of 2,8-DHA into renal parenchyma (DHA nephropathy). DHA nephropathy occurs most often in patients with repeated misdiagnosed episodes of urolithiasis and progressive worsening of renal function, but it may also present as acute renal failure. Rarely, DHA nephropathy may occur in patients who experienced only a few stone episodes. DHA nephropathy can evolve to end stage renal disease requiring dialysis and transplantation and can recur after transplantation causing rapid loss of graft function if left untreated.

Etiology
APRT deficiency is an autosomal recessive (AR) disorder caused by mutations in the APRT gene (16q24) encoding the APRT enzyme catalyzing AMP synthesis from adenine and 5'-phosphoribosyl-1-pyrophosphate. Two types of APRT deficiencies have been described, according to APRT activity in vitro; type I characterized by a total lack of APRT activity, found primarily in Caucasians, and type II, found only in Japan, characterized by a 10-25% APRT activity. This in vitro distinction has no known clinical significance.

Diagnostic methods
Lack of awareness of APRT deficiency often causes a significant delay between the onset of symptoms and a proper diagnosis. Diagnosis is primarily based on identifying 2,8-DHA by examination of crystals or stones. Crystalluria examination can be used for diagnosis. In DHA nephropathy patients, crystals may also be identified in renal biopsy, although this invasive test is theoretically unnecessary. Crystals and stones should be analyzed by morphologic examination combined with infrared spectrometry and/or x-ray crystallography. Diagnosis can be confirmed by enzyme activity analysis in erythrocyte lysates. Genetic testing may be used for diagnosis but may be useful for familial screening.

Differential diagnosis
Confusion frequently occurs between 2,8-DHA and uric acid stones, which are typically both radiolucent. Contrary to uric acid, 2,8-DHA stones do not respond to alkali therapy. Differential diagnosis also includes other radiolucent stones, such as cystine, xanthine and drugs.

Genetic counseling
Genetic counseling is possible but rarely indicated. However, given the AR transmission, siblings of the affected individual, even if they are asymptomatic, should be screened through DNA analysis or APRT activity.

Management and treatment
To prevent further 2,8-DHA formation, treatment consists of allopurinol daily (usually 10mg/kg per day in children and 300 mg per day in adults) together with a high fluid intake and low purine diet. In cases of acute or chronic renal failure, allopurinol doses should be reduced. Asymptomatic individuals should be treated by allopurinol to prevent renal complications. Febuxostat, another xanthine oxydase inhibitor, may be even more efficacious than allopurinol in reducing DHA excretion. It remains unknown how this translates into improved patient outcomes. Febuxostat should be recommended in allopurinol-intolerant patients and also in rare patients who do not respond well to allopurinol.

Prognosis
Early diagnosis is the key and prognosis depends on progression of this treatable disorder. Allopurinol therapy effectively prevents stone recurrence and can lead to an improvement or stabilization of renal function in most patients. Stone recurrence and renal complications are rare in patients who remain compliant with allopurinol therapy.

Visit the Orphanet disease page for more resources.

Symptoms

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
Abnormal enzyme/coenzyme activity
0012379
30%-79% of people have these symptoms
Acute kidney injury
0001919
Dysuria
Painful or difficult urination
0100518
Hypertension
0000822
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
5%-29% of people have these symptoms
Abdominal colic
0011848
Atrial fibrillation
Quivering upper heart chambers resulting in irregular heartbeat
0005110
Flank pain
0030157
Macroscopic hematuria
Bloody urine
0012587
Oliguria
0100520
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
Uric acid nephrolithiasis
Uric acid stones
0000791
Urinary hesitancy
Difficulty with flow
0000019
Urinary retention
0000016
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Nephrolithiasis
Kidney stones
0000787
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083

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 Adenine phosphoribosyltransferase deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

  • 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 Adenine phosphoribosyltransferase deficiency. Click on the link to view a sample search on this topic.