中国儿童Shwachman-Diamond综合征的临床诊治循证研究

Diagnosis and treatment of Shwachman-Diamond syndrome in Chinese children:an evidence-based study

目的探索我国儿童Shwachman-Diamond综合征(SDS)的临床表型及基因型特征,以供早期诊断参考。方法以"Shwachman-Diamond综合征""SDS""SBDS基因""遗传性骨髓衰竭"等为关键词,设定检索年限为2002年1月至2022年10月,检索在万方数据和中国知网数据库相关文献。同时以"Shwachman-Diamond syndrome"为关键词,检索2002年1月至2022年10月内Web of Science和美国医学文摘数据库(PubMed)的文献报道病例,包含上海市同济医院治疗的1例SDS患儿,共计44例作为研究对象。参照《国际SDS诊断标准》作为诊断标准,应用χ2检验和t检验统计学分析,以系统回顾的方式进行循证研究,对资料完整的44例临床数据进行病例系列研究,归纳我国儿童SDS流行病学、临床特征和早期诊断要点,并与国际病例资料进行对比。结果中国儿童SDS主要特征归纳如下:(1)男女比例大约为1.3∶1,起病中位年龄为3个月,诊断中位年龄为14个月,相对起病年龄滞后。(2)常见首发症状为胰腺消化酶缺乏(31.8%)和中性粒细胞减少伴感染(31.8%)。国际共识所示SDS三类主要病变发生率分别为血细胞减少(95.4%),胰腺病变(72.7%)和骨骼异常(40.9%)。(3)SDS常见致病SBDS基因变异位点为c.258+2T>C和c.183184TA>CT,其表型与临床表现无明显相关性(P>0.05)。(4)与国际报道比较,中国儿童SDS三系减少的发生率与部分亚洲国家及北美地区均存在一定差异(P<0.05),基因变异也存在一定种族差异。结论儿童SDS起病年龄早,个体差异明显。需加强病例报道和资料汇总,以提高临床对于SDS的认识和早期诊断率,以利及时实施有效临床干预措施。

Objective To explore the characteristics of Shwachman-Diamond syndrome(SDS)in Chinese children in order to provide a reference for early diagnosis.Methods With Shwachman-Diamond syndrome,SDS,SBDS gene and inherited bone marrow failure as the keywords,the search period was set from January 2002 to October 2022.Relevant literature was retrieved from the Wanfang Database and China National Knowledge Infrastructure(CNKI)database.In addition,using Shwachman-Diamond syndrome as the keyword,the search was also carried out on the Web of Science,PubMed,and MEDLINE databases from January 2002 to October 2022.A child with SDS treated at the Tongji Hospital was also included.A total of 44 cases with complete clinical data were analyzed with reference to the International Standard for SDS Diagnosis.Chi-square test and t test were used for statistical analysis.Evidence-based research was carried out in the form of systematic review.The epidemiology,clinical characteristics and key points of early diagnosis of the Chinese SDS children were summarized and compared with the international data.Results The main characteristics of SDS in Chinese children were summarized as follows:The ratio of males to females was about 1.3:1,the median age of onset was 3 months,and the median age of diagnosis was 14 months.The first symptoms were often exocrine pancreatic insufficiency(31.8%)and granulocytopenia with infection(31.8%).According to the international consensus,the incidence rates of the three major diseases of SDS were hemocytopenia(95.4%),pancreatic disease(72.7%),and bone abnormality(40.9%).The common factors underlying SDS disease were variants of the SBDS gene(c.258+2T>C and c.183_184TA>CT),albeit there was no significant correlation between genotype and phenotype(P>0.05).Compared with international reports,the clinical manifestations and genotypes of Chinese SDS children are different(P<0.05).Conclusion The SDS children have an early age of onset and significant individual difference.It is necessary to analyze the case-related data to facilitate early recognition,diagnosis and clinical intervention.