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Adenine Phosphoribosyltransferase Deficiency.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2012 Aug 30 [updated 2015 Jun 18].

Author information

1
Division of Pediatric Nephrology, Children´s Medical Center, Landspítali - The National University Hospital of Iceland, Reykjavik, Iceland
2
Division of Nephrology, Landspítali - The National University Hospital of Iceland, University of Iceland, Reykjavik, Iceland
3
Department of Genetics, Rutgers University, Piscataway, New Jersey

Excerpt

CLINICAL CHARACTERISTICS:

Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production of 2,8-dihydroxyadenine (DHA), which is excreted in the urine, where it is poorly soluble and leads to kidney stone formation and chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected individuals symptoms do not occur until adulthood. In a significant number of individuals, intratubular and interstitial precipitation of DHA crystals can result in kidney failure (i.e., DHA crystal nephropathy).

DIAGNOSIS/TESTING:

The detection of the characteristic round, brown DHA crystals by urine microscopy is highly suggestive of the disorder. The diagnosis is confirmed by absence of APRT enzyme activity in red cell lysates or identification of biallelic pathogenic variants in APRT.

MANAGEMENT:

Treatment of manifestations: Treatment with the xanthine dehydrogenase (XDH) inhibitor allopurinol can prevent or dissolve kidney stones and improve kidney function, even in individuals with advanced CKD. The XDH inhibitor febuxostat is an alternative option for those allergic to or intolerant of allopurinol. A low purine diet and ample fluid intake are recommended. Surgical management of DHA nephrolithiasis is the same as for other types of kidney stones. End-stage renal disease is treated with dialysis and kidney transplantation. Prevention of primary manifestations: Lifelong treatment with allopurinol (or febuxostat) prevents or attenuates DHA crystalluria, nephrolithiasis, crystal nephropathy, and the development of kidney failure. The prescribed allopurinol dose should not routinely be reduced in affected individuals who have impaired kidney function. Surveillance: Routine follow-up to facilitate medication compliance; consideration of periodic renal ultrasound examination to evaluate for new kidney stones. Agents/circumstances to avoid: Azathioprine should be avoided by individuals taking XDH inhibitors. Evaluation of relatives at risk: It is recommended that sibs of an affected individual undergo APRT enzyme activity measurement or molecular genetic testing (if the pathogenic variants in a family have been identified) to allow early diagnosis and treatment and improve long-term outcome. Pregnancy management: The safety of allopurinol in human pregnancy has not been systematically studied. Some post-transplantation immunosuppressive therapies can have adverse effects on the developing fetus. Ideally a thorough discussion of the risks and benefits of maternal medication use during pregnancy should take place with an appropriate health care provider prior to conception.

GENETIC COUNSELING:

APRT deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being normal. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

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