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Kidney Week

Abstract: PO1358

Refractory Hypocalcemia with Recurrent Nephrolithiasis Related to a De Novo Gain-of-Function Mutation in the CaSR Gene

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Tan, Xin Yee, Cleveland Clinic, Cleveland, Ohio, United States
  • Khan, Leila Zeinab, Cleveland Clinic, Cleveland, Ohio, United States
  • Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States

The calcium-sensing receptor (CASR) serves as the key calcium sensor in the maintenance of systemic calcium homeostasis. Gain-of-function mutations of CaSR-gene, mapped to Ala116-Pro136 region, causes autosomal dominant hypocalcemia and Bartter syndrome type V. Phenotypic manifestations include hypercalciuric hypocalcemia(mostly asymptomatic), hypoparathyroidism, paresthesias, tetany/ epilepsy, nephrocalcinosis/ nephrolithiasis, hypomagnesemia, ectopic and intracranial calcifications. Here we report a case of gravid female who experienced refractory hypocalcemia with recurrent nephrolithiasis related to a de novo gain-of-function mutation in the CASR gene.

Case Description

A 25 year-old G1P0 female at 20 weeks of gestation presented to genetic nephrology clinic due to refractory hypocalcemia. She was incidentally found to have asymptomatic hypocalcemia as part of prenatal evaluation. She was treated with calcium and calcitriol for four months while hypocalcemia persisted. Physical exam was unremarkable. As shown in Table 1, her total serum calcium had been persistently low despite calcium and Vitamin D supplementations, and she had low PTH, hyperphosphatemia, hypomagnesemia, and hypercalciuria. Genetic testing revealed a variant (c.398A>T,pGlu133Val) in CASR gene, with negative parental testing consistent with de novo mutation. Given this finding, calcium and calcitriol were discontinued. Renal ultrasound to assess stone burden showed bilateral renal calculi, which patient passed during delivery. Recurrent renal calculi were discovered on post-delivery follow up imaging, necessitating laser lithotripsy and left ureteral stent insertion.


This case highlights the importance of early diagnoses by genetic testing which could guide the hypocalcemia management, as routine calcium and vitamin D supplementation exacerbates hypercalciuria and thus risk of nephrocalcinosis/ nephrolithiasis. c.398A>T,pGlu133Val mutation has been described in 1 family cluster of 3 patients with hypoparathyroidism and hypocalcemia to date. De novo mutation, unique to this case, was evidenced by negative parental testing.