Kidney Week

Abstract: SA-PO0166

Twenty Years of Recurrent Nephrolithiasis Revealing an Atypical Heterozygous CYP24A1 Phenotype

Session Information

• Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Batish, Ishaan, Mayo Clinic in Florida, Jacksonville, Florida, United States

Ishaan Batish, MBBS

• Fatfat, Adnan, Mayo Clinic in Florida, Jacksonville, Florida, United States

Adnan Fatfat, MD

• Sharma, Abhinav, Mayo Clinic in Florida, Jacksonville, Florida, United States

Abhinav Sharma, MBBS

• Kafrouni Gerges, Antoni, Mayo Clinic in Florida, Jacksonville, Florida, United States

Antoni Kafrouni Gerges, MD

• Bobart, Shane A., Mayo Clinic in Florida, Jacksonville, Florida, United States

Shane A. Bobart, MD, FASN

• Khambati, Ibrahim, Mayo Clinic in Florida, Jacksonville, Florida, United States

Ibrahim Khambati, MD, MBA, FASN

Introduction

Recurrent calcium nephrolithiasis with persistent hypercalciuria is often considered idiopathic after exclusion of secondary causes. Monogenic disorders of calcium and vitamin D metabolism are possible in atypical or longstanding cases; although CYP24A1-related disease is classically autosomal recessive, we report an adult with recurrent nephrolithiasis and marked hypercalciuria due to a heterozygous pathogenic CYP24A1 variant despite the absence of overt hypercalcemia.

Case Description

A 56-year-old man presented with a 20 year history of recurrent nephrolithiasis and persistent hypercalciuria. Prior stone analysis demonstrated a composition of 80% calcium oxalate and 20% calcium phosphate. Nine months prior, he developed left flank pain and was found to have a 1.4-cm left proximal ureteral calculus requiring ureteroscopic laser lithotripsy. Metabolic evaluation revealed normal serum calcium and 25-hydroxyvitamin D levels, and parathyroid hormone was normal to low-normal. However, there was marked hypercalciuria, peaking at 902 mg/24 hours and remaining persistently above 400 mg/day despite dietary modification, hydration, and sodium restriction. Bone density testing showed osteopenia. The degree and persistence of hypercalciuria were out of proportion to typical idiopathic hypercalciuria and raised concern for a monogenic cause. Genetic testing identified a pathogenic heterozygous CYP24A1 variant, c.1186C>T (p.Arg396Trp). Additional biochemical evaluation demonstrated a 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D ratio of 13.57, which, in the genetic context, was interpreted as supportive of altered vitamin D catabolism.

Discussion

This case highlights a clinically significant renal phenotype associated with a monoallelic pathogenic CYP24A1 variant in the absence of overt hypercalcemia. Emerging data suggest that monoallelic CYP24A1 variants may result in a spectrum of disease due to reduced enzymatic reserve, including recurrent nephrolithiasis, persistent hypercalciuria, and abnormal vitamin D metabolism. This case broadens the recognized phenotype of CYP24A1-related disease and underscores the importance of considering genetic testing in adults with longstanding, severe, or persistent hypercalciuric stone disease despite intervention, with direct therapeutic implications including avoidance of unnecessary vitamin D supplementation and tailored management of recurrent stone disease.