钙敏感受体信号通路相关高钙血症患儿的临床及遗传学分析

Clinical and genetic analysis of children with calcium-sensing receptor signaling pathway related hypercalcemia

本研究探讨钙敏感受体(CaSR)信号通路相关高钙血症患儿的临床特点、基因变异类型及随访资料。采用回顾性收集2017年7月至2022年11月首都儿科研究所内分泌科诊治的6例高钙血症患儿的临床资料并进行致病基因测序,分析其临床特征和基因变异特点及转归。结果显示,6例患儿是男3例、女3例,就诊时年龄范围在2个月至8岁之间,临床表现从无症状到呕吐、脱水、生长迟缓及智力低下、癫痫不等,除1例血钙显著升高外(4.63 mmol/L),余病例血钙波动于2.98~3.17 mmol/L,6例患者中5例甲状旁腺激素(parathyroid hormone,PTH)升高,1例正常;3例24 h尿钙/尿肌酐清除率明显降低。全外显子测序发现1例CaSR复合杂合变异、4例CaSR杂合变异,1例AP2S1杂合变异。明确诊断后1例行甲状旁腺全切术,术后钙剂补充治疗,3例予鲑降钙素,2例低钙饮食,血钙均控制在正常水平。综上,CaSR信号通路相关高钙血症较为罕见,基因检测为明确诊断的主要方法。家族性低尿钙性高钙血症(FHH)应用鲑降钙素治疗可收到良好效果。

To analyze the clinical characteristics and follow-up data of Chinese patients with calcium-sensing receptor(CaSR)signaling pathway related hypercalcemia.A retrospective analysis was conducted on six children with hypercalcemia admitted to Department of Endocrinology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2017 to November 2022.Summarized the clinical and pathogenic variants,as well as follow-up data.The results showed that 3 were female and 3 were male of the 6 cases,aged from 2 months to 8 years at the consultation.The clinical symptoms varied from asymptomatic hypercalcemia to vomiting,dehydration,and growth retardation,as well as epilepsy and intellectual disability.Except for 1 case,which showed a significant increase in blood calcium(4.63 mmol/L),the blood calcium of other cases ranged from 2.98 to 3.17 mmol/L.Among the 6 patients,5 had elevated parathyroid hormone,and 1 was normal.Three cases showed a significant decrease in 24-hour urinary calcium to creatinine ratio.Whole exome sequencing revealed that one patient had compound heterozygous variants and four had a heterozygous variants of CaSR gene,one patient had a heterozygous variant of AP2S1 gene.1 case underwent total parathyroidectomy,followed by calcium supplementation,3 cases received salmon calcitonin treatment,and 2 cases accepted low calcium diet,blood calcium levels were all controlled well.In conclusion,CaSR signaling pathway related hypercalcemia is rare.Gene detection is essential for children with hypercalcemia.Familial hypocalcemia hypercalcemia(FHH)can be effectively treated with salmon calcitonin.