Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Eur J Endocrinol. 2020 Dec;183(6):K13-K21. doi: 10.1530/EJE-20-0710.
Gain-of-function mutations in the CASR gene cause Autosomal Dominant Hypocalcemia Type 1 (ADH1), the most common genetic cause of isolated hypoparathyroidism. Subjects have increased calcium sensitivity in the renal tubule, leading to increased urinary calcium excretion, nephrocalcinosis and nephrolithiasis when compared with other causes of hypoparathyroidism. The traditional approach to treatment includes activated vitamin D but this further increases urinary calcium excretion.
In this case series, we describe the use of recombinant human parathyroid hormone (rhPTH)1-84 to treat subjects with ADH1, with improved control of serum and urinary calcium levels.
We describe two children and one adult with ADH1 due to heterozygous CASR mutations who were treated with rhPTH(1-84). Case 1 was a 9.4-year-old female whose 24-h urinary calcium decreased from 7.5 to 3.9 mg/kg at 1 year. Calcitriol and calcium supplementation were discontinued after titration of rhPTH(1-84). Case 2 was a 9.5-year-old male whose 24-h urinary calcium decreased from 11.7 to 1.7 mg/kg at 1 year, and calcitriol was also discontinued. Case 3 was a 24-year-old female whose treatment was switched from multi-dose teriparatide to daily rhPTH(1-84). All three subjects achieved or maintained target serum levels of calcium and normal or improved urinary calcium levels with daily rhPTH(1-84) monotherapy.
We have described three subjects with ADH1 who were treated effectively with rhPTH(1-84). In all cases, hypercalciuria improved by comparison to treatment with conventional therapy consisting of calcium supplementation and calcitriol.
CASR 基因的功能获得性突变导致常染色体显性低钙血症 1 型（ADH1），这是孤立性甲状旁腺功能减退症最常见的遗传原因。与其他原因引起的甲状旁腺功能减退症相比，这些患者的肾小管钙敏感性增加，导致尿钙排泄增加、肾钙质沉着症和肾结石。传统的治疗方法包括活性维生素 D，但这会进一步增加尿钙排泄。
在本病例系列中，我们描述了使用重组人甲状旁腺激素（rhPTH）1-84 治疗 ADH1 患者，以改善血清和尿钙水平的控制。
我们描述了 3 例 ADH1 患者，他们均为杂合性 CASR 突变所致，使用 rhPTH(1-84)治疗。病例 1 为 9.4 岁女性，24 小时尿钙从治疗前的 7.5 降至 1 年后的 3.9mg/kg。rhPTH(1-84)滴定后停用了骨化三醇和钙补充剂。病例 2 为 9.5 岁男性，24 小时尿钙从 11.7 降至 1 年后的 1.7mg/kg，也停用了骨化三醇。病例 3 为 24 岁女性，治疗方案从多剂量特立帕肽转换为每日 rhPTH(1-84)。所有 3 例患者在接受 rhPTH(1-84)单药治疗后均达到或维持了目标血清钙水平，且尿钙正常或改善。
我们描述了 3 例 ADH1 患者，他们用 rhPTH(1-84)治疗有效。与钙补充和骨化三醇组成的常规治疗相比，所有患者的高钙尿症均有改善。
