Identification of p.Arg205Cys in CASR in an autosomal dominant hypocalcaemia type 1 pedigree

Abstract

Rationale: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene ( CASR ), which produces a left-shift in the set point for extracellular calcium. Patient concerns: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR , c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family. Diagnosis: The patient was diagnosed with ADH1 clinically and genetically. Interventions: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient. Outcomes: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved. Lessons: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.

Autosomal dominant hypocalcemia with a novel CASR mutation: a case study and literature review

“…Additionally, calcilytics are under development for the treatment of ADH1, while thiazide-like diuretics have been used to treat hypercalciuria. 24 Our patient continued to receive calcium supplements and antiepileptic drugs to avoid the recurrence of epilepsy.…”