Venous Thrombosis in a Pseudohypoparathyroidism Patient with a Novel GNAS Frameshift Mutation and Complete Resolution of Vascular Calcifications with Acetazolamide Treatment.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Hormone Research in Paediatrics Pub Date : 2024-01-01 Epub Date: 2023-10-31 DOI:10.1159/000534456
Tuba Seven Menevse, Yorihiro Iwasaki, Zehra Yavas Abali, Busra Gurpinar Tosun, Didem Helvacioglu, Ömer Dogru, Onur Bugdayci, Sajin M Cyr, Tulay Güran, Abdullah Bereket, Murat Bastepe, Serap Turan
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引用次数: 0

Abstract

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 nonhormonal 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 parathyroid hormone, 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.

一名患有新型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血管钙化。
引言IA型假性甲状旁腺功能减退症(PHP1A)的特征是末端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作用受损。然而,尚未描述有血栓事件的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。病例介绍一名女性患者在117/12岁时出现身材矮小、疲劳和运动引起的拼车痉挛。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畸形。在GNAS的最后一个外显子中检测到一种新的移码变体(c.1065_1068delGCGT,p.R356Tfs*47),显示转染细胞中基线和受体刺激活性完全丧失。在右侧静脉穿刺和左侧治疗期间葡萄糖酸钙外渗后,患者出现了静脉血栓形成和前臂血管及皮下钙化。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失。结论该病例是第一例出现血栓形成的PHP1A患者,也是第一例成功使用乙酰唑胺治疗PHP1A相关软组织钙化的患者,从而为该疾病的非内分泌特征的治疗提供了新的见解。
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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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