Abstract: SA-PO0172
Hiding in Plain Sight: Adult CYP24A1 Deficiency Presenting with CKD, Nephrolithiasis, and Calcific Coronary Disease
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
- Arabyat, Mahmoud, Saint Louis University, St. Louis, Missouri, United States
- Malhotra, Kunal, Saint Louis University, St. Louis, Missouri, United States
Introduction
CYP24A1 encodes 24-hydroxylase, which catabolizes 1,25-dihydroxyvitamin D. Biallelic loss-of-function variants cause unregulated calcitriol activity, producing hypercalcemia, hypercalciuria, nephrolithiasis, and renal injury. Historically pediatric, it can evade diagnosis for decades with cumulative renal and vascular consequences.
Case Description
A 65-year-old male athlete presented with chronic kidney disease stage 3 (estimated glomerular filtration rate 41 mL/min/1.73 m), hypercalcemia (calcium 11.4 mg/dL), and recurrent nephrolithiasis. As a teenager, he had hematuria dismissed as "runner's kidney" without workup. Calcium stones followed from 1998 (three lithotripsies); 24-hour urine showed elevated oxalate, phosphate, and brushite supersaturation. Labs revealed suppressed parathyroid hormone (PTH, 10 pg/mL), normal 25- and 1,25-dihydroxyvitamin D, and a negative PTH-related peptide (PTHrP). Angiotensin-converting enzyme (ACE) was elevated in 2019 (78 U/L) but normalized (26 U/L); imaging excluded granulomatous disease. In August 2025 he suffered out-of-hospital ventricular fibrillation (VF) arrest during exercise; catheterization revealed severe calcific distal left main and proximal-to-mid left anterior descending disease requiring intravascular lithotripsy and ultrasound-guided percutaneous coronary intervention, with staged right coronary intervention. Genetic testing confirmed a homozygous, likely pathogenic CYP24A1 variant.
Discussion
First, exertional hematuria in young athletes warrants biochemical screening, as CYP24A1-driven hypercalciuria can masquerade as mechanical hematuria. Second, hypercalcemia with suppressed PTH, negative PTHrP, and recurrent calcium stones should prompt CYP24A1 testing once granulomatous disease and malignancy are excluded; anchoring on a single elevated ACE may delay diagnosis. Third, lifelong calcitriol excess drives accelerated vascular calcification; this patient's calcific left main and VF arrest at 65 likely reflect decades-long calcium dysregulation rather than atherosclerosis alone.
CYP24A1 deficiency is not exclusively pediatric. Recognition in adults with unexplained hypercalcemia, suppressed PTH, and stones can prevent irreversible renal and cardiovascular sequelae.