2,8 dihydroxy-adenine urolithiasis

File:Autorecessive.svg Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Synonyms and keywords: Adenine phosphoribosyltransferase deficiency; AMP pyrophorylase deficiency; APRT deficiency

2,8 dihydroxy-adenine urolithiasis is a genetic disorder in which deficiency of the enzyme adenine phosphoribosyltransferase leads to nephrolithiasis, permanent kidney damage and eventually chronic renal failure.

• The disease is an autosomal recessive disorder associated with a mutation in the enzyme adenine phosphoribosyltransferase.
• The enzyme catalyzes the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme to recycle adenine into nucleic acids.
• Deficiency of this enzyme leads to excess formation and hyperexcretion of 2,8 dihydroxy adenine (DHA) into urine.
• Low solubility of DHA results in precipitation of this compound and the formation of crystals and stones.

• More than 300 individuals with this disorder have been reported so far, out of which two thirds were from Japan, and a substantial number from France and Iceland.
• The estimated prevalence of APRT deficiency 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 ^{[1] [2]}

• Nephrolithiasis
• Chronic renal failure

• Associated with renal stones:
  • Colicky pain
  • Hematuria
  • Dysuria
  • Oliguria
  • Reddish brown diaper spots in younger children
• Associated with chronic renal failure:
  • Nausea/ Vomiting
  • Weakness and fatigue
  • Anorexia and weight loss
• Occasionally, patients may also complain of eye discomfort.

• Patient may appear to be in distress from colicky flank pain and/or uremia

In advanced cases with signs of chronic renal failure,

• Blood pressure may be elevated.
• Patient may be tachypneic from metabolic acidosis associated with uremia.

• Conjunctiva may appear hyperemic from eye discomfort.

• Patients with renal compromise may have a ventricular heave.
• Auscultation
  • S4 may be heard
  • Pericardial friction rub in those with chronic uremia.

• Auscultation
  • Crackles
  • Decreased breath sounds from pulmonary edema in those who develop chronic renal failure.

Early recognition and treatment of APRT deficiency is crucial in preventing irreversible damage to the kidneys.

• Stone analysis: 2,8 DHA crystals are readily detectable in the urine.
• Crystalluria: The small and medium sized crystals have a central maltese cross pattern on polarized light microscopy whereas the large crystals do not as they are impermeable to light .

• APRT activity in hemolysates of erythrocytes.

• 2,8 Dihydro adenine stones are radiolucent, hence not detected on X-ray films.

• Renal stones are easily detectable on CT scan.

• Ultrasonography is highly sensitive for detecting renal stones.

• Easily differentiates 2,8 DHA stones from uric acid stones.

• Identifying mutations in both copies of the APRT gene.

• Allopurinol: 5-10 mg/kg/day (maximum dose of 600-800 mg/day). Side effects include skin rash and gastrointestinal intolerance, hypersensitivity.
• Patients who do not tolerate allopurinol, febuxostat (a xanthine oxidase inhibitor) or oxypurinol (a xanthine dehydrogenase inhibitor) should be considered.

• Plenty of fluids
• Dietary purine restriction.

• Patients treated with allopurinol can be followed up by monitoring urine microscopy.

• Approximately 30% of patients require intervention for stone removal
  • Extracorporeal shock-wave lithotripsy,
  • Lithotomy and
  • Endourological procedures

• Adenine phosphoribosyltransferase

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