Introduction Pseudohypoparathyroidism type IA (PHP1A) is characterized by end-organ resistance to multiple hormones and Albright's hereditary osteodystrophy (AHO). PHP1A is caused by inactivating mutations of the GNAS gene encoding the α-subunit of the stimulatory G protein (Gsα). In line with the underlying genetic defect, impaired inhibition of platelet aggregation has been demonstrated in some patients. However, no PHP1A case with thrombotic events has been described. Also, PHP1A cases typically have subcutaneous ossifications, but soft tissue calcifications are another common finding. Treatment options for those and other non-hormonal features of PHP1A are limited. Case Presentation A female patient presented with short stature, fatigue, and exercise-induced carpopedal spasms at age 117/12 years. Diagnosis of PHP1A was made based on hypocalcemia, hyperphosphatemia, elevated serum PTH, and AHO features, including short stature and brachydactyly. A novel frameshift variant was detected in the last exon of GNAS (c.1065_1068delGCGT, p.R356Tfs*47), showing complete loss of baseline and receptor-stimulated activity in transfected cells. The patient developed venous thrombosis and vascular and subcutaneous calcifications on both forearms after venous puncture on the right and extravasation of calcium gluconate during treatment on the left. The thrombosis and calcifications completely resolved following treatment with low molecular weight heparin and acetazolamide for 5 and 8 months, respectively. Conclusions This case represents the first PHP1A patient displaying thrombosis and the first successful use of acetazolamide for PHP1A-associated soft tissue calcifications, thus providing new insights into the treatment of non-endocrinological features in this disease.

中文翻译：

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患有新型 GNAS 移码突变的假性甲状旁腺功能减退症患者的静脉血栓形成，并通过乙酰唑胺治疗完全消除了血管钙化。

简介 IA 型假性甲状旁腺功能减退症 (PHP1A) 的特点是终末器官对多种激素的抵抗和奥尔布赖特遗传性骨营养不良 (AHO)。PHP1A 是由编码刺激性 G 蛋白 (Gsα) α 亚基的 GNAS 基因失活突变引起的。与潜在的遗传缺陷一致，一些患者的血小板聚集抑制功能受损。然而，尚未描述发生血栓事件的 PHP1A 病例。此外，PHP1A 病例通常有皮下骨化，但软组织钙化是另一个常见的发现。PHP1A 的这些和其他非激素特征的治疗选择是有限的。病例介绍 一名 117/12 岁女性患者因身材矮小、疲劳和运动引起的手足痉挛就诊。PHP1A 的诊断基于低钙血症、高磷血症、血清 PTH 升高和 AHO 特征，包括身材矮小和短指。在 GNAS 最后一个外显子 (c.1065_1068delGCGT, p.R356Tfs*47) 中检测到一种新的移码变异，显示转染细胞中基线和受体刺激活性完全丧失。患者右侧静脉穿刺后，左侧治疗时葡萄糖酸钙外渗，出现静脉血栓，双前臂出现血管和皮下钙化。分别用低分子肝素和乙酰唑胺治疗5个月和8个月后，血栓形成和钙化完全消退。结论 该病例代表了首例出现血栓形成的 PHP1A 患者，也是首次成功使用乙酰唑胺治疗 PHP1A 相关软组织钙化，从而为该疾病非内分泌特征的治疗提供了新的见解。