A Family of Autosomal Dominant Hypocalcemia with an Activating Mutation of Calcium-Sensing Receptor Gene

Endocrine Journal

TOSHIRO FUJITA²  NORIKO CHIKATSU¹  SUMIYO WATANABE²  YASUSHI MURAOSA¹  YUJI OKA¹  SEIJI FUKUMOTO²  SHINSUKE SASAKI¹  YASUHIRO TAKEUCHI² 

[1] Department of Internal Medicine and Pediatrics, Hitachi General Hospital;Department of Internal Medicine and Laboratory Medicine, University of Tokyo School of Medicine

关键词: Autosomal dominant hypocalcemia;    CaSR;    Activating mutation;   

DOI  :  10.1507/endocrj.50.91

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(16)Cited-By(8)Autosomal dominant hypocalcemia (ADH) caused by activating mutations of calcium-sensing receptor (CaSR) is characterized by hypocalcemia with inappropriately low concentration of PTH and relative hypercalciuria. Active vitamin D treatment often leads to nephrolithiasis and renal impairment in patients with ADH. However, differential diagnosis between ADH and idiopathic hypoparathyroidism is sometimes very difficult. Here, we report a mutation of CaSR and its functional property found in three generations of a Japanese family. The proband developed seizures at 7 days of age. His mother and elder sister were discovered to have hypoparathyroidism by family survey, but his father was normocalcemic. His grandfather developed heart failure and was found to have hypoparathyroidism. All affected members had been treated with active vitamin D3 and bilateral nephrolithiasis were detected in three of them. DNA sequencing revealed that all affected patients had a heterozygous mutation in CaSR gene that causes proline to leucine substitution at codon 221 (P221L). In vitro functional analysis of the mutant CaSR by measuring inositol 1,4,5-trisphosphate production in response to changes of extracellular Ca indicated that this mutation is an activating one and responsible for ADH in this family. Therefore, careful monitoring of urinary Ca excretion before and during treatment of PTH-deficient hypoparathyroidism is very important, and screening of CaSR mutation should be considered in patients with relative hypercalciuria or with a family history of hypocalcemia.

【 授权许可】

Unknown