Bone Abstracts

Objectives: Several genes have been recognized to be associated with nonsurgical hypoparathyroidism. Most previous studies focused on gene mutation among paediatric hypoparathyroidism patients. Data about gene mutations in adult-onset hypoparathyroidism patients is still lacking. This study was designed to evaluate the role of gene defects in the pathogenesis of adult-onset hypoparathyroidism in China through the targeted next-generation sequencing (NGS).

Subjects and methods: We recruited 17 patients with adult-onset nonsurgical hypoparathyroidism who were regularly followed or newly diagnosed at our centre during the past one year. Nine of them developed hypercalciuria during the treatment with calcium and vitamin D agents. None of them had physical deformity or family history of hypoparathyroidism. Targeted NGS was performed to screen 10 related genes, including AIRE, AP2S1, CASR, CLDN16, FAM111A, GATA3, GCM2, PTH, TBCE and TRPM6.

Results: A novel homozygosis mutation of GCMB gene [c.130G>A (p.G44S)] was identified which was predicted to be deleterious by PolyPhen2. The patient was a 36-year-old woman who suffered from paroxysmal carpopedal spasms in the menstrual cycle for ten years. Before treatment, the serum calcium and phosphorus was 1.48 mmol/l and 2.29 mmol/l, respectively. And the PTH concentration was lower than 3.0 pg/ml. intracranial calcification and cataract were also identified. During treatment with calcium and vitamin D, she developed hypercalciuria when her serum calcium reached 2.04 mmol/l. Hydrochlorothiazide was administered. No evidence of urolithiasis was found.

Conclusions: In this study, we identified the genetic defect only in 1 patient (5.9%). In adult-onset nonsurgical hypoparathyroidism without other diagnostic clues, the gene mutation screening as the first choice to clarify the aetiology was not recommended.