2,8 dihydroxy-adenine urolithiasis
File:Autorecessive.svg
Synonyms and keywords: Adenine phosphoribosyltransferase deficiency; AMP pyrophorylase deficiency; APRT deficiency

# Overview
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.

# Pathophysiology

## Genetics
- 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.

# Epidemiology and Demographics
- 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  

# Natural History, Complications and Prognosis

## Complications
- Nephrolithiasis
- Chronic renal failure

# Diagnosis

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

## Physical examination

### Appearance of the Patient
- Patient may appear to be in distress from colicky flank pain and/or uremia

### Vital Signs
In advanced cases with signs of chronic renal failure,
- Blood pressure may be elevated.
- Patient may be tachypneic from metabolic acidosis associated with uremia.

### Eyes
- Conjunctiva may appear hyperemic from eye discomfort.

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

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

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

### Urinalysis
- 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 .

### Blood tests
- APRT activity in hemolysates of erythrocytes.

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

### CT
- Renal stones are easily detectable on CT scan.

### Ultrasonography
- Ultrasonography is highly sensitive for detecting renal stones.

### Spectrophotometry and Crystallography
- Easily differentiates 2,8 DHA stones from uric acid stones.

### Genetic Testing
- Identifying mutations in both copies of the APRT gene.

# Treatment

## Pharmacotherapy
- 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.

## Patient Education
- Plenty of fluids
- Dietary purine restriction.

## Follow up
- Patients treated with allopurinol can be followed up by monitoring urine microscopy.

## Surgery and Device based therapy
- Approximately 30% of patients require intervention for stone removal
Extracorporeal shock-wave lithotripsy,
Lithotomy and
Endourological procedures
- Extracorporeal shock-wave lithotripsy,
- Lithotomy and
- Endourological procedures