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Adenine phosphoribosyltransferase (APRT)

Adenine phosphoribosyl transferase (APRT)



Overview

Adenine phosphoribosyl transferase (APRT) deficiency is a rare, inherited metabolic disorder where the body cannot properly process adenine. This leads to the build-up of insoluble 2,8-dihydroxyadenine (2,8-DHA) crystals, which form kidney stones and can cause severe, progressive kidney damage.

Symptoms

Symptoms vary widely, and roughly half of all affected individuals remain completely asymptomatic until adulthood.

When symptoms do occur, they typically involve the genitourinary system:

Reddish-Brown Diaper Stains: Often the very first sign in infants, caused by the excretion of DHA crystals.

Nephrolithiasis (Kidney Stones): Recurrent stones that cause flank pain, abdominal cramps, nausea, and vomiting.

Urinary Issues: Blood in the urine (hematuria), pain or difficulty during urination, and frequent urinary tract infections (UTIs).

Kidney Damage: Crystalline nephropathy can cause sudden acute kidney injury (AKI) or progressive chronic kidney disease (CKD). If unrecognized, it can eventually lead to end-stage renal disease (ESRD).

Causes

Kidney & Urinary Stones: This is the most common symptom, affecting roughly 60% to 90% of patients. The stones are often radiolucent, meaning they can be hard to spot on standard X-rays.

Crystalline Nephropathy: DHA crystals can precipitate directly into the renal tubules and tissues, causing inflammation and damage.

Pediatric Signs: In infants and babies, the first sign is often the passing of tiny reddish-brown grains in the diaper.

Urinary Blockages: Stones can cause intense abdominal pain, blood in the urine (hematuria), nausea, and recurrent urinary tract infections.

Renal Failure: If left unmanaged, crystal accumulation can cause acute kidney injury, chronic kidney disease (CKD), and eventually end-stage renal disease

Diagnosis

Urine & Stone Analysis:

Crystal Examination: 2,8-dihydroxyadenine (2,8-DHA) crystals are highly insoluble and often appear as characteristic "oat-shaped" or spherical crystals under polarized light microscopy.

Stone Analysis: Suspicious kidney or urinary stones should be analyzed using advanced techniques like infrared spectroscopy or mass spectrometry, as routine chemical analysis can yield false positives.

Enzyme Activity Measurement: Diagnosis can be confirmed by analyzing red blood cell (erythrocyte) lysates to check for absent or severely reduced APRT enzyme activity. It differentiates between Type I (complete enzyme absence) and Type II (intact cell enzyme function but abnormal lysate function, most common in Japanese populations).

Genetic Testing: APRT gene mutation analysis provides a definitive confirmation. This testing is often conducted via multi-gene panels for kidney stones or targeted APRT gene sequencing to identify biallelic pathogenic variants

Treatment

Management for APRT deficiency relies heavily on a combination of specific medications, dietary changes, and regular Kidney Care UK monitoring:

Pharmacotherapy (Medication)Allopurinol: The primary, lifelong medication used to inhibit the enzyme that creates DHA stones. Standard doses range from 5 to 10 mg/kg/day or 300 to 600 mg/day in adults.

Febuxostat: Prescribed as an alternative (usually 80 mg/day) for patients who experience adverse side effects from Allopurinol.

Dietary Adjustments Low-Purine Diet: Limits purine-heavy foods like red meat, shellfish, and beer, which can contribute to stone formation.

Hydration High Fluid Intake: Drinking ample amounts of water helps dilute the urine and decreases the supersaturation and crystallization of DHA.

Unlike other kidney stones, DHA stones are highly insoluble regardless of urine pH, meaning alkaline treatments are ineffective.

Clinical Monitoring: The success of the treatment is typically evaluated via urine microscopy; the goal is the complete absence of urinary 2,8-DHA crystals.

Intervention: Larger stones that cannot be dissolved or passed may require urological procedures, such as lithotripsy or endoscopy.

Transplant: If the condition progresses to end-stage renal failure, pre-transplant treatment with these inhibitors is critical to prevent the disease from recurring in the transplanted kidney.

Type of Doctor Department :  A Nephrologist (kidney specialist)

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