Shwachman-Diamond综合征三例临床诊治和基因分析

背景Shwachman-Diamond综合征（SDS）是一种罕见的常染色体隐性遗传病，临床表现复杂多样，随着基因组测序的应用和临床灵敏性的提高，对儿童和成人SDS的诊断较前明显增多，但国内多数SDS患者诊断后缺乏系统规范的治疗。目的分析3例SDS患儿的临床特征和诊疗经过，以增强临床医生对该病的认识，减少漏诊和误诊，规范确诊患儿的治疗方案。方法收集2018年10月至2020年10月在北京大学第一医院儿科治疗的3例SDS患儿的临床表现、实验室检查、基因分析、治疗方案和随访情况等资料，结合相关文献，分析并总结儿童SDS的临床诊治经过。结果3例SDS患儿中2例为女性，1例为男性，均有反复感染、脂肪泻、身材矮小及营养不良等表现，例2有并指畸形。辅助检查提示3例患儿均有中性粒细胞减少，例1合并重度贫血，例2合并血小板减少；3例患儿均有肝功能异常，均为SBDS基因复合杂合突变，突变位点均为c.258+2T>C和c.184A>T。治疗方面，3例患儿均给予胰酶替代、营养支持、保肝等治疗；例1需要依赖红细胞输注，给予小剂量泼尼松治疗后贫血明显改善。结论SDS为多系统受累疾病，早期进行基因检测可以提高诊断率，治疗上需给予多学科综合治疗。减低剂量预处理的造血干细胞移植能改善SDS患儿的部分临床表现，但需严格掌握移植适应证。对于红系增生低下且暂时不具备造血干细胞移植条件的SDS患儿可以试用小剂量短疗程的糖皮质激素治疗，以减轻对血制品的依赖。

Clinical Management and Genetic Features of 3 Cases of Shwachman-Diamond Syndrome

Background Shwachman-Diamond syndrome(SDS)is a rare autosomal recessive genetic disease that has complex and various clinical presentations.With the increase in application and clinical sensitivity of genome sequencing,the diagnoses of SDS in children and adults using genome sequencing have increased significantly,but most Chinese SDS patients have not received systematic and standardized treatment after diagnosis.Objective To analyze the clinical characteristics,diagnosis and treatment of three children with SDS,expecting to improve clinicians'recognition of this disease,reduce the possibilities of missed diagnosis and misdiagnosis,and standardize the treatment of diagnosed children.Methods Data of three children with SDS were collected from Department of Pediatrics,Peking University First Hospital from October 2018 to October 2020,including clinical manifestations,laboratory examination,gene analysis,treatment and follow-up,and were analyzed.In combination with the review of other relevant literature,the diagnosis and treatment of pediatric cases of SDS were summarized.Results Among the three cases encountered and treated by us,two were female and one was male.All of them had recurrent infection,fatty diarrhea,short stature and malnutrition.Case 2 also had syndactyly.Auxiliary tests suggested that all these cases had neutropenia and abnormal liver function.Besides that,case 1 also had severe anemia,and case 2 had thrombocytopenia.Two compound heterozygous mutations of SBDS gene,that is,c.258+2T>C and c.184A>T,were found in all three cases.For treatment,all three patients were given pancreatic enzyme replacement therapy,nutritional support,and hepatoprotective treatment.The anemia of case 1,which was dependent on suspended red blood cell transfusion,was obviously improved after low-dose prednisone treatment.Conclusion SDS is a disease with multiple systems involved.Gene detection is helpful to the early diagnosis of SDS.Comprehensive,multidisciplinary treatment is needed.Hematopoietic stem cell transplantation with reduced dose pretreatment can improve some clinical manifestations,but the transplantation indications should be strictly controlled.Low dose and short course of glucocorticoid could be used to reduce the dependence on blood products for those with low erythropoiesis and no hematopoietic stem cell transplantation conditions.