Abstract:
Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding TPSAB1 copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.
摘要:
遗传性α-类胰蛋白酶血症(HαT)是一种常染色体显性(AD)遗传性状,其特征是基础血清类胰蛋白酶升高≥8ng/mL,由编码TPSAB1的α-类胰蛋白酶拷贝数增加引起。HαT影响5%至7%的西方人群,并与关节过度活动有关。高流动性障碍同样经常是AD,但是遗传病因往往难以捉摸。高迁移率谱系障碍个体的基因分型(n=132),超机动Ehlers-Danlos综合征(n=78),或轴性骨骼异常伴过度活动(n=56)。比较了有和没有HαT的个体的临床特征。在分析我们的组合队列时,吞咽困难(p=0.007)和原牙列残留(p=0.0003)与HαT显著相关,而与过敏反应(p=0.07)和瘙痒(P=0.5)的正相关没有达到显著性,可能是由于样本量有限.总的来说,HαT患病率在患有过度活动障碍的个体中没有增加,而与独特的内型有关,证明HαT如何改变复杂患者的临床表现。