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Objective <p>Autosomal dominant hypocalcemia type 1 (ADH1) is rarely reported in Chinese populations except for isolated cases. This study aimed to describe the clinical characteristics of a group of Chinese patients with genetically confirmed childhood-onset ADH1 and compare them with patients diagnosed with idiopathic hypoparathyroidism (IHP).</p> Methods <p>This retrospective study analyzed 210 childhood-onset hypoparathyroidism (HP) cases using targeted next-generation sequencing and TBX1-MLPA. Patients harboring rare variants in the <i>CASR</i> gene were identified as ADH1 cases. In vitro functional tests of the variants were performed using a dual-luciferase reporter assay. Patients without any variants or with only benign/likely benign variants in known HP-related genes were classified as IHP for comparison. Clinical presentation, biochemical parameters, and complications were compared between the ADH1 and IHP groups.</p> Results <p>Thirteen ADH1 patients carried 10 different <i>CASR</i> mutations, including six novel variants, all of which showed higher NFAT activity in functional tests. Median age at hypocalcemia onset was 0.05 years, with an average diagnostic delay of 12.90 ± 9.90 years. Four of them were familial cases. Compared to 124 IHP patients, ADH1 patients showed significantly earlier onset (0.05 vs. 12.67 years), higher 24&#xa0;h urinary calcium excretion (0.13 vs. 0.04 mmol/kg/day) despite similar serum calcium levels, more frequent hypomagnesemia (61.54 vs. 13.73%), and more urolithiasis (38.46 vs. 10.00%).</p> Conclusion <p>This study extends the known <i>CASR</i> mutation spectrum in ADH1 and highlights key clinical features (early onset, family history, hypomagnesemia, hypercalciuria, and urolithiasis) that may indicate ADH1. It is suggested that the genotyping should be clarified as early as possible in clinical practice, which is crucial for accurate diagnosis and the formulation of effective, personalized treatment strategies.</p>

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Clinical characteristics of chinese patients with autosomal dominant hypocalcemia type 1: a single-center study

  • 期刊论文

  • 发表日期：

    2026年3月9日

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  • Yiyang Gao,
  • Yue Jiang,
  • Yabing Wang,
  • Jing Yang,
  • Jiajia Wang,
  • An Song,
  • Yan Jiang,
  • Mei Li,
  • Weibo Xia,
  • Xiaoping Xing,
  • Min Nie,
  • Ou Wang

摘要

Objective

Autosomal dominant hypocalcemia type 1 (ADH1) is rarely reported in Chinese populations except for isolated cases. This study aimed to describe the clinical characteristics of a group of Chinese patients with genetically confirmed childhood-onset ADH1 and compare them with patients diagnosed with idiopathic hypoparathyroidism (IHP).

Methods

This retrospective study analyzed 210 childhood-onset hypoparathyroidism (HP) cases using targeted next-generation sequencing and TBX1-MLPA. Patients harboring rare variants in the CASR gene were identified as ADH1 cases. In vitro functional tests of the variants were performed using a dual-luciferase reporter assay. Patients without any variants or with only benign/likely benign variants in known HP-related genes were classified as IHP for comparison. Clinical presentation, biochemical parameters, and complications were compared between the ADH1 and IHP groups.

Results

Thirteen ADH1 patients carried 10 different CASR mutations, including six novel variants, all of which showed higher NFAT activity in functional tests. Median age at hypocalcemia onset was 0.05 years, with an average diagnostic delay of 12.90 ± 9.90 years. Four of them were familial cases. Compared to 124 IHP patients, ADH1 patients showed significantly earlier onset (0.05 vs. 12.67 years), higher 24 h urinary calcium excretion (0.13 vs. 0.04 mmol/kg/day) despite similar serum calcium levels, more frequent hypomagnesemia (61.54 vs. 13.73%), and more urolithiasis (38.46 vs. 10.00%).

Conclusion

This study extends the known CASR mutation spectrum in ADH1 and highlights key clinical features (early onset, family history, hypomagnesemia, hypercalciuria, and urolithiasis) that may indicate ADH1. It is suggested that the genotyping should be clarified as early as possible in clinical practice, which is crucial for accurate diagnosis and the formulation of effective, personalized treatment strategies.