软骨-毛发发育不全(CHH)是一种综合征性免疫缺陷,其特征是干phy端发育不良,癌症易感性,和不同程度的贫血。在婴儿期可能表现为严重的联合免疫缺陷,或缓慢进展,直到在青春期后期/成年期完全显现。目前没有针对性的治疗,患者通常通过支持性措施来管理,或提供骨髓移植,如果临床表型是严重的,一个合适的供体是可用的。我们报告了一个年轻女孩的病例,该女孩表现为输血依赖性红细胞生成衰竭和类似自身免疫性淋巴增生综合征的免疫学特征,对经验性西罗莫司反应良好。她后来出现了明显的生长延迟,这最终归因于干phy端发育不良。通过全基因组测序(WGS)诊断为CHH,在不太敏感的基因诊断策略失败后。由于表现为隐球菌性脑膜脑炎的进行性联合免疫缺陷,患者最终接受了单倍体相同的骨髓移植。这个案例说明了西罗莫司在纠正贫血和部分控制与CHH相关的免疫畸变中的潜在作用。并提醒人们WGS在诊断具有复杂和非典型表现的患者中的宝贵作用。
Cartilage-hair hypoplasia (CHH) is a syndromic immunodeficiency characterized by metaphyseal dysplasia, cancer predisposition, and varying degrees of anemia. It may present as severe combined immunodeficiency in infancy, or slowly progress until fully manifesting in late adolescence/adulthood. No targeted treatment is currently available, and patients are usually managed with supportive measures, or are offered a bone marrow transplant if the clinical phenotype is severe and a suitable donor is available. We report the
case of a young girl presenting with transfusion-dependent erythropoietic failure and immunological features resembling autoimmune lymphoproliferative syndrome who responded well to empirical sirolimus. She later developed a marked growth delay, which was ultimately attributed to metaphyseal dysplasia. A diagnosis of CHH was reached through whole-genome sequencing (WGS), after a less sensitive genetic diagnostic strategy failed. The patient eventually underwent a haploidentical bone marrow transplant due to progressive combined immunodeficiency manifested as cryptococcal meningoencephalitis. This
case illustrates the potential role of sirolimus in correcting anemia and partially controlling the immune aberrations associated with CHH, and serves as a reminder of the invaluable role of WGS in diagnosing patients with complex and atypical presentations.