Adenine phosphoribosyltransferase (APRT) deficiency is an underrecognized, autosomal recessive disorder of adenine metabolism, leading to 2,8-dihydroxyadeninuria that causes radiolucent nephrolithiasis and kidney failure in a significant proportion of untreated patients. A minority of patients may, however, be asymptomatic. APRT deficiency occurs in both men and women and affects both children and adults. Most reported cases come from Japan, France and Iceland but an increasing number of patients are being identified in other countries, including the United States.

Estimated prevalence is 0.5 to 1 per 100,000 in the Caucasian population, 0.25 to 0.5 per 100,000 in the Japanese population and in Iceland the estimated point prevalence is 8.9/100,000. Likely explanation for the low prevalence in other countries include lack of awareness of the disorder, inadequate evaluation of patients with kidney stones, and erroneous diagnosis of 2,8-dihydroxyadenine (2,8-DHA) stones as uric acid or xanthine stones as they are all radiolucent.  

The diagnosis of APRT deficiency is simple as the typical 2,8-DHA urinary crystals are readily detected by urine microscopy. All patients with radiolucent kidney stones and patients with presumed uric acid stones, who do not respond to alkali therapy but improve with allopurinol treatment, should be screened for APRT deficiency. The diagnosis can also be made with APRT mutation analysis of or measurement of APRT enzyme activity in red cell lysates. Analysis of 2,8-DHA crystals and stone material with infrared and ultraviolet spectrophotometry and/or x-ray crystallography easily differentiates 2,8-DHA from uric acid.  

Allopurinol, when administered in the dose of 5-10 mg/kg/day (maximum suggested daily dose 600-800 mg) effectively prevents 2,8-DHA crystalluria and new stone formation and significantly improves kidney function in most patients with reduced renal function. In patients who do not tolerate allopurinol therapy febuxostat (Uloric®) treatment should be considered. Treatment should be monitored with urine microscopy at follow-up visits. The prognosis of adequately treated patients is excellent. 

Lack of recognition of the disorder by clinicians is likely to remain a problem leading to unnecessary morbidity and mortality in affected patients. Increased awareness of APRT deficiency among physicians is needed to improve outcome in this group of patients.