# Successful Treatment With Evocalcet Against Familial Hypocalciuric Hypercalcemia Type 3 (FHH3) Identified by AP2S1 Gene Mutation (p.Arg15Leu)

## TL;DR

A 21-year-old woman with a rare genetic disorder causing high blood calcium levels was successfully treated with a new drug called evocalcet.

## Contribution

This case demonstrates that evocalcet, a calcium-sensing receptor agonist, can effectively treat FHH3 caused by an AP2S1 gene mutation.

## Key findings

- Evocalcet normalized serum calcium levels in a patient with FHH3.
- The treatment improved bone metabolism without serious side effects.
- The patient had a confirmed AP2S1 gene mutation (p.Arg15Leu).

## Abstract

Background: Familial hypocalciuric hypercalcemia type 3 (FHH3) is a rare hereditary disorder caused by a heterozygous AP2S1 gene mutation, characterized by hypocalciuria and hypercalcemia due to impaired intracellular signal transduction of calcium (Ca)-sensing receptors (CaSRs). All affected patients harbored a heterozygous missense mutation at the Arg15 residue of the encoded AP2σ1.

Case Presentation: A 21-year-old female was referred to our hospital with hypercalcemia and reduced bone mineral density (BMD) detected during a preoperative examination for scoliosis surgery. She had a developmental disorder and exhibited hypocalciuria on urinalysis. Genetic testing revealed a heterozygous AP2S1 gene mutation (p.Arg15Leu), and the patient was diagnosed with FHH3. In the present case, we investigated the effects of evocalcet, a newly approved CaSR agonist. Treatment with evocalcet gradually decreased and normalized the serum Ca level, and promoted improvements in bone metabolism, without serious adverse events.

Conclusion: Evocalcet may be a promising therapeutic candidate for symptomatic FHH3.