新生儿严重甲状旁腺功能亢进症:基因型/表现型间相关性和应用pamidronate作为抢救措施  

Neonatal severe hyperparathyroidism: Genotype/phenotype correlation and the use of pamidronate as rescue therapy

作　　者：Waller S. Kurzawinski T. Spitz L. W.G.Van’t Hoff 高蕊 

机构地区：[1]Nephro-Urology Unit, Univ. Coll. of London Med. Schools, Hospital for Children NHS Trust, Great Ormond Street, WC1N 3JH London, United Kingdom

出　　处：《世界核心医学期刊文摘（儿科学分册）》2005年第3期31-31,共1页

摘　　要：家族性低尿钙性高钙血症(FHH)是一种常染色体显性遗传性疾病。该病因钙敏感受体(CaSR)的基因发生杂合性突变引起。而在那些CaSR的基因纯合性突变的患儿则会罹患新生儿严重甲状旁腺功能亢进(NSHPT)症。与相对良性且无症状的:FHH不同,NSHPT 者如果不进行甲状旁腺切除则有生命危险。笔者报道了3例NSHPT病例。Familial hypocalciuric hypercalcaemia (FHH) is an auto-somal dominant condition due to heterozygous loss of function calcium sensing receptor (CaSR) mutations. However, individuals who are homozygous for CaSR mutations have neonatal severe hyperparathyroidism(NSHPT), which unlike the relatively benign and asymptomatic FHH can be fatal without parathyroidectomy. We report three patients with NSHPT associated with marked hypercalcaemia and severe hyperparathyroidism with related skeletal deminer-alisation. We describe the novel use of intravenous pamidronate in NSHPT, to control severe hypercalcaemia in these patients prior to parathyroidectomy and in one individual as a rescue therapy to stabilise life-threatening demineralisation. Furthermore, a marked phenotypic heterogeneity was observed amongst four members from a large kindred with the same homozygous CaSR mutations: one patient would have died without parathyroidectomy in infancy; a second patient survived infancy but underwent parathyroidectomy in early childhood following severe symptomatic hypercalcaemic episodes; whilst the other two patients have survived to adolescence without parathyroidectomy. Additionally, in contrast to the literature these two individuals suffered minimal morbidity. Conclusions: we commend the short-term use of pamidronate in neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt hyperparathyroid-driven skeletal demineralisation in preparation for parathyroidectomy. The remarkable de- gree of phenotypic variation demonstrated remains unexplained without functional studies; this variability highlights the challenge of treating this rare condition.

关 键 词：PAMIDRONATE 高钙血症 甲状旁腺切除 钙敏感受体 生命危险 表现型 纯合性 无症状 杂合性 遗传性疾病 

分 类 号：R722.1[医药卫生—儿科]