Abstract: SA-PO0168
Double Heterozygosity of Variants in CYP24A1 and Sucrase-Isomaltase in a Patient with Rapidly Recurrent Nephrolithiasis
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
- Roberts, Samuel, Oregon Health & Science University, Portland, Oregon, United States
- White, Misah Ann, Oregon Health & Science University, Portland, Oregon, United States
- Gustafson, Kate S., Portland VA Medical Center, Portland, Oregon, United States
Introduction
The CYP24A1 gene encodes 24-hydroxylase which inactivates Vitamin D metabolites, loss-of-function thereby leads to calcium dysregulation. Homozygous mutations of CYP24A1 are associated with hypercalcemia and nephrocalcinosis in infancy; however, cases of nephrolithiasis are also described with heterozygote mutations. Congenital sucrase-isomaltase deficiency is autosomal recessive and is associated with infant failure to thrive and nephrocalcinosis; heterozygote individuals are noted to develop irritable bowel syndrome and nephrocalcinosis, though the pathogenesis of the latter is incompletely described.
Case Description
A 49-year-old male with nephrolithiasis presented with acute flank pain and was found to have acute renal failure with and a moderate burden of non-obstructive bilateral renal stones by axial imaging. He reported passing 1-2 stones every month for many years, and multiple prior stone analyses with composition >90% Ca-oxalate monohydrate, minor 0-2% Ca-oxalate dihydrate, and 0-10% Ca-phosphate. Family history was notable for nonspecific cystic kidney disease in his mother, maternal aunt, and grandmother. He previously tried thiazide and citrate without reduction in stone burden. Prior urologic evaluation has previously noted calcification in all calyces. Renal function improved with IV fluids and usual care. At outpatient follow-up 1 month later, the patient reported passing four stones in the interval period; given the family history and frequency of stone formation, genetic testing was obtained to further delineate the driver of his high stone burden. Results of genetic testing disclosed heterozygous mutations in CYP24A1 (c.1226T>C [p.Leu409Ser]) and SI (c5204T>G[p.Phe1745Cys), which are associated with hypercalcemia, nephrolithiasis, and nephrocalcinosis. In addition to high fluid intake, he resumed citrate supplementation and thiazide diuretic with reduction in stone frequency to an average of one every 6 weeks.
Discussion
This case is notable for the presence of two mutations which, together, are the likely drivers of the patient's remarkable stone formation rate. Given the family history of non-specific cystic kidney disease, the differential strongly considered medullary sponge kidney, nephronophthisis, and medullary cystic kidney disease. Genetic testing helped outline the drivers of disease and aides with counseling regarding heritability.