Adenine phosphoribosyltransferase deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited disorder of purine metabolism caused by mutations in the APRT gene located on chromosome 16q24.3. The enzyme APRT normally converts adenine to adenosine monophosphate (AMP). When this enzyme is deficient, adenine is instead oxidized by xanthine dehydrogenase to 2,8-dihydroxyadenine (2,8-DHA), a highly insoluble compound that precipitates in the urine and kidney tissue. The disease is also known as 2,8-dihydroxyadenine urolithiasis or DHA crystalluria. The condition primarily affects the urinary system and kidneys. The hallmark clinical features include recurrent kidney stones composed of 2,8-DHA, crystalluria, and progressive kidney damage that can lead to chronic kidney disease and even end-stage renal failure if left untreated. Stones made of 2,8-DHA are radiolucent and can be misidentified as uric acid stones, which frequently leads to delayed or missed diagnosis. Symptoms can present at any age, from infancy through adulthood, and include renal colic, hematuria, urinary tract infections, and renal insufficiency. Some patients may remain asymptomatic for years before diagnosis. Two types of APRT deficiency have been described: Type I (complete enzyme deficiency, found worldwide) and Type II (partial enzyme deficiency, reported predominantly in Japanese populations). Treatment centers on the use of allopurinol or febuxostat, which are xanthine dehydrogenase inhibitors that block the conversion of adenine to 2,8-DHA. These medications are highly effective at preventing stone formation and preserving kidney function when started early. High fluid intake and dietary purine restriction are also recommended as supportive measures. Early diagnosis and lifelong treatment are essential to prevent irreversible kidney damage, and the prognosis is generally favorable with appropriate therapy.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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