APRT Deficiency / DHA

Adenine phosphoribosyltransferase (APRT) deficiency is an uncommon genetic disorder that often causes kidney stones, and in some patients kidney failure. More than 300 individuals with this disease have been reported world-wide but it is not known how common this medical problem truly is. Patients with the disease deficiency lack the enzyme adenine phosphoribosyltransferase and therefore have difficulties breaking down dietary substances called purines, resulting in accumulation of a compound called 2,8-dihydroxyadenine (2,8-DHA) that is excreted by the kidneys. 2,8-DHA is poorly soluble in the urine leads to the formation of kidney stones and kidney injury. Interestingly, up to 70% of affected patients, have red hair or relatives with this hair color.

Most patients with APRT deficiency have repeated episodes of kidney stones that are not detected by a conventional x-ray study. However, all stones are easily detected by other medical imaging methods such as ultrasound or computerized tomography (CT) scan. A minority of patients develop symptoms of kidney failure. Kidney stones are often associated with severe loin or abdominal pain. Symptoms associated with kidney failure are largely nonspecific such as increased fatigue and weakness, poor appetite, and weight loss. Children with the disease may have similar symptoms as adults. In young children, APRT deficiency can cause reddish-brown diaper spots.

Doctors can diagnose this condition by examining the urine sediment through a microscope, where typical 2,8-DHA crystals can readily be detected (Figure 1.). However, most physicians and other health care providers are unlikely to be familiar with this disorder and may not recognize the crystals if present in the urine. The diagnosis can also be made by analysis of any kidney stone material that has passed, or by genetic methods. APRT deficiency should be considered in all patients with kidney stones and in patients presenting with kidney failure of unknown cause.

If you suspect that you may have APRT deficiency, you should ask you doctor to order a microscopic examination of your urine to search for the typical crystals (Figures 1a and 1b), and a blood test (serum creatinine) that measures kidney function. An ultrasound examination, or a computed tomography scan of your kidneys may identify kidney stones that are not detected on a regular x-ray.

Allopurinol is an effective and generally well tolerated medication that blocks the production of 2,8-DHA, and therefore, prevents recurrent kidney stone formation and kidney failure. A few patients cannot tolerate allopurinol due to allergy or other side effects. Unfortunately, no alternative medical therapy is currently available. Patients who develop kidney stone attacks that do not resolve spontaneously, require treatment by a urologist to remove the stone. Treatment options include lithotripsy which employs sound waves to break the stones into smaller pieces that can pass in the urine, or surgical procedures to remove the stone. Endoscopy is the surgical method used in most cases. Open surgery for removal of stones is only rarely required.

A retrospective study published by our group clearly shows that allopurinol prevents stone recurrence and even reverses established renal failure in properly treated patients. However, more study is necessary to evaluate the effectiveness of existing treatment options (allopurinol), to identify other treatment strategies, and to monitor the clinical outcome of patients with APRT deficiency.

The Consortium aims to establish a registry for patients with APRT deficiency. We will update this information as progress is made.

Currently, no patient support organizations devoted to APRT deficiency exist. However, if you or your physician or other health care providers have questions about the diagnosis of APRT deficiency, or care of patients who have this problem, please do not hesitate to contact Vidar Edvardsson, MD (vidare@landspitali.is) and/or Runolfur Palsson, MD (runolfur@landspitali.is) at Landspitali University Hospital in Reykjavik, Iceland (paging operator: 354 – 543-1000).

More information on APRT deficiency can be located through the OMIM® - Online Mendelian Inheritance in Man® database.