Shen Yingxiao, Yang Wei, He Qin, Xu Xiaoqin, Sun Yan, Wang Zhihua, Yang Xiaohong, Dong Guanping, Huang Ke, Wei Haiyan, Wu Wei, Fu Junfen
Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310051, China.
Department of Endocrinology, Genetics and Metabolism, Henan Children's Hospital, Zhengzhou Children's Hospital, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, China.
J Endocrinol Invest. 2025 Feb;48(2):393-400. doi: 10.1007/s40618-024-02465-5. Epub 2024 Nov 12.
This study was aimed to analyze the clinical and genetic characteristics of hypoparathyroidism in children.
We performed a retrospective analysis of 74 patients diagnosed with pediatric hypoparathyroidism from 2014 to 2023, recruited in five medical centers across China. Data of basic information and clinical tests were extracted from patients' records. Whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis (CMA) were utilized to identify the genetic causes.
The results indicated a median onset age of 6.07 ± 4.82 years and a median diagnosis age of 6.91 ± 4.88 years. Of the 46 patients who underwent genetic tests, 35 were found to carry pathogenic variants related to hypoparathyroidism. Specifically, 19 cases (19/46, 41.30%) had 22q11.2 microdeletion, while other variations included AIRE (8/46, 17.39%), GATA3 (3/46, 6.52%), CaSR (2/46, 4.34%), and the rest 3 patients with mutations of TBCE, PTH and mitochondrial gene deletion respectively. Convulsions were the most common initial presentation, observed in 43 cases. The non-DGS group exhibited the lowest serum PTH levels compared to DiGeorge syndrome and gene-negative group. Among the 66 patients who underwent cranial CT or MR, 26 (26/66, 39.99%) presented with intracranial calcification.
We reported the largest cohort of childhood hypoparathyroidism with genetic diagnoses, reinforcing the view that genetic disorders account for the majority of pediatric hypoparathyroidism, with the 22q11.2 microdeletion being the most prevalent. Identifying the genetic causes of hypoparathyroidism is crucial for predicting patient outcomes, managing comorbidities, and, importantly, informing decisions regarding the potential use of emerging recombinant human PTH therapy.
本研究旨在分析儿童甲状旁腺功能减退症的临床和遗传特征。
我们对2014年至2023年在中国五个医疗中心招募的74例诊断为儿童甲状旁腺功能减退症的患者进行了回顾性分析。从患者记录中提取基本信息和临床检查数据。采用全外显子组测序（WES）、多重连接依赖探针扩增（MLPA）和染色体微阵列分析（CMA）来确定遗传病因。
结果显示发病年龄中位数为6.07±4.82岁，诊断年龄中位数为6.91±4.88岁。在46例接受基因检测的患者中，35例被发现携带与甲状旁腺功能减退症相关的致病变异。具体而言，19例（19/46，41.30%）有22q11.2微缺失，其他变异包括AIRE（8/46，17.39%）、GATA3（3/46，6.52%）、CaSR（2/46，4.34%），其余3例患者分别有TBCE、PTH突变和线粒体基因缺失。惊厥是最常见的首发表现，43例患者出现。与迪乔治综合征组和基因阴性组相比，非迪乔治综合征组血清甲状旁腺激素水平最低。在66例接受头颅CT或磁共振成像（MR）检查的患者中，26例（26/66，39.99%）出现颅内钙化。
我们报告了最大规模的一组有基因诊断的儿童甲状旁腺功能减退症病例，进一步证明了遗传疾病是儿童甲状旁腺功能减退症的主要病因，其中22q11.2微缺失最为常见。确定甲状旁腺功能减退症的遗传病因对于预测患者预后、管理合并症至关重要，重要的是，可为有关新兴重组人甲状旁腺激素疗法潜在应用的决策提供依据。
