Shwachman-Diamond综合征8例病例系列报告

doi:10.3969/j.issn.1673-5501.2021.02.013

摘要/Abstract

摘要： 背景 Shwachman-Diamond综合征(SDS)主要表现为骨髓衰竭、胰腺外分泌功能不全、骨骼异常三联征。约90%SDS患儿为SBDS基因突变,EFL1、DNAJC21、SRP54基因突变也可导致SDS样综合征。既往报道SBDS基因型与血液表型无明显相关性。目的总结SDS患儿的临床特征,探究SBDS基因型与表型的相关性。设计病例系列报告。方法回顾性收集复旦大学附属儿科医院临床免疫科2016年1月至2020年11月诊治的SDS病例,总结其临床表现、免疫表型及基因结果。主要结局指标 不同基因型的临床指标(感染、中性粒细胞数量、预后等)。结果共纳入8例SDS患儿,男3例,女5例,起病中位年龄2.2月,确诊中位年龄8.5月。家系WES检测示,5例为SBDS基因c.183_184TA>CT/c.258+2T>C复合杂合突变,均以感染起病,表现为反复呼吸道感染、脓毒血症、皮肤软组织感染,伴粒细胞缺乏;2例为SBDS基因c.258+2T>C纯合突变,感染程度较轻,其中1例合并粒细胞缺乏;1例主要表现为反复皮肤脓肿、重症肺炎、脓毒血症,伴粒细胞缺乏,骨髓细胞学检查提示粒系发育停滞于早幼粒水平,家系WES发现SRP54基因新发杂合突变[c.349_351del(p.T117del)]。结论反复感染和粒细胞缺乏是部分SDS患儿的首发表现,临床医生应对这类患儿尽早进行系统的免疫表型和基因型评估,以期早期诊断。

关键词: Shwachman-Diamond综合征, SBDS, SRP54, 粒细胞缺乏, 免疫缺陷

Abstract: Background Shwachman-Diamond syndrome (SDS) is a rare immunodeficiency disorder characterized by bone marrow failure, pancreatic exocrine insufficiency, and skeletal abnormalities. About 90% of SDS patients had SBDS gene mutations. In addition, EFL1, DNAJC21 and SRP54 mutations had also been described in patients with SDS-like syndrome. It had been reported that there was no significant correlation between SBDS genotype and blood phenotype.Objective To summarize the clinical characteristics of patients with SDS, and to analyze genotype-phenotype correlation.DesignCase series report.Methods Patients with SDS treated in the Department of Clinical Immunology, Children's Hospital of Fudan University from January 2016 to November 2020 were enrolled. The clinical manifestations, immunophenotype and gene analysis were summarized.Main outcome measures Clinical indicators of patients with different genotypes (infection, neutrophil counts, prognosis, etc).Results A total of 8 patients(3 males and 5 females) with confirmed SDS were included. The median age of onset was 2.2 months and the median age at diagnosis was 8.5 months. Whole-exome sequencing (WES) showed that 5 cases had SBDS c.183_184TA>CT/c.258+2T>C compound heterozygous mutations, who were first presented with infections accompanied by neutropenia, including recurrent respiratory tract infections, septic and soft tissue infections; 2 cases had SBDS c.258+2T>C homozygous mutations who both had mild infection, among whom 1 patient was complicated with neutropenia; 1 case had SRP54 mutation (c.349_351del, p. T117del) with main manifestations of recurrent skin abscess, severe pneumonia and sepsis accompanied by neutropenia.The bone marrow cytology showed that neutrophil lineage and maturation arrested at the promyelocyte stage.Conclusion Some patients with SDS may present with infection and neutropenia as the first symptoms. Systematic assessment of the immunophenotype and genotype should be performed to achieve a definite diagnosis.

Key words: Shwachman-Diamond syndrome, SBDS, SRP54, Neutropenia, Immunodeficiency

杨蜜, 孙碧君, 侯佳, 王文婕, 应文静, 惠晓莹, 孙金峤, 王晓川. Shwachman-Diamond综合征8例病例系列报告[J]. 中国循证儿科杂志, 2021, 16(2): 146-151.

YANG Mi, SUN Bijun, HOU Jia, WANG Wenjie, YING Wenjing, HUI Xiaoying, SUN Jinqiao, WANG Xiaochuan. 8 cases of Shwachman-Diamond syndrome: A case series report[J]. Chinese Journal of Evidence-Based Pediatrics, 2021, 16(2): 146-151.

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