A Rare Genetic Mutation in a Stone Former

Area of Science:

• Nephrology
• Medical Genetics
• Biochemistry

Background:

• Recurrent kidney stones (nephrolithiasis) can indicate underlying metabolic or genetic disorders.
• Chronic kidney disease (CKD) in young adults necessitates thorough etiological investigation.
• Dihydroxy adenine (DHA) crystalline nephropathy is a rare inherited disorder of purine metabolism.

Observation:

• A 30-year-old woman presented with acute kidney injury, edema, and hypertension, alongside a history of childhood nephrolithiasis.
• Renal biopsy revealed chronic interstitial nephritis with characteristic greenish-brown refractile crystals.
• Metabolic work-up was negative, prompting consideration of genetic causes.

Findings:

• Spectrophotometry confirmed deficient Adenine phosphoribosyl-transferase (APRT) enzyme activity in red blood cell lysates.
• Genetic analysis identified a novel missense mutation in the APRT gene (exon 3) in the patient and her family.
• This mutation is associated with dihydroxy adenine crystalline nephropathy, a rare cause of nephrolithiasis and CKD.

Implications:

• Highlights the importance of considering DHA crystalline nephropathy in young patients with unexplained nephrolithiasis and CKD.
• Emphasizes the role of genetic testing in diagnosing rare inherited kidney diseases.
• Reports the first identification of this specific APRT gene mutation in India, contributing to global genetic databases.