以肝损害起病的Shwachman-Diamond综合征两例报告并文献复习

Shwachman-Diamond syndrome starting with liver damage:two cases report and literature review

目的探讨常染色体隐性遗传病Shwachman-Diamond综合征(Shwachman-Diamond syndrome,SDS)患儿的临床特点和基因学特征。方法收集2019年4—10月首都儿科研究所附属儿童医院收治的以肝损害为主要表现的2例SDS患儿的临床资料,对患儿的临床特点、影像学表现、基因测序结果、治疗情况及随访结果进行系统性分析,并查阅相关文献。结果2例患儿均以肝功能异常为主要表现起病并就诊,ALT为129~291 U/L。起病隐匿,均在2岁之内发病,表现为体质量和身高明显落后,低于正常同龄儿相应参考值的第3百分位点。例2有反复呼吸道感染,均不伴有脂肪泻。2例均伴有持续性/间歇性中性粒细胞减少(最低值为0.5×10^(9)/L和0.28×10^(9)/L)。例2存在动脉导管未闭,腹部CT示胰腺脂肪化,双股骨X线片示右侧髋关节间隙稍增宽。2例患儿SBDS基因检测确诊,例1为c.183_184delinsCT及c.258+2T>C的复合杂合突变,例2为c.183_184delinsCT杂合突变及c.258+2T>C纯合突变。治疗主要为胰酶替代治疗及营养支持治疗。治疗后2例患儿身高、体重均稳步增长,监测中性粒细胞计数维持稳定。以“Shwachman-Diamond”“SBDS”为关键词,查阅文献并复习,已报道病例中以肝损害起病者较少,首发表现多以生长发育迟缓、血象异常及脂肪泻被重视并得以就诊。结论SDS患儿常见临床表现为胰腺脂肪化和外分泌不足、外周血象中至少一系下降,尤其中性粒细胞减少和骨骼异常。部分患儿以肝功能异常隐匿起病,需提高对本疾病的认识,SBDS基因检测有助于确诊。

Objective To investigate the clinical and genetic characteristics of children with Shwachman-Diamond syndrome(SDS).Methods The clinical data of two children who suffered from SDS and with liver damage as the main manifestation in Children’s Hospital Affiliated to Capital Institute of Pediatrics from April to October 2019 were colllected.The clinical characteristics,imaging manifestations,results of gene sequencing,treatment and follow-up were systematically analyzed,and relevant literatures were reviewed.Results Abnormal liver function was the main manifestation of the two children,and ALT was 129-291 U/L.The onset of the disease was insidious,and the age of onset was within two years old.The development of body weight and height lagged behind significantly,which was lower than the third percentile of the corresponding reference value of normal same age children.Case two had recurrent respiratory tract infection without fatty diarrhea.Both cases were accompanied with persistent/intermittent neutropenia(minimum values were 0.5×10^(9)/L,0.28×10^(9)/L respectively).Case two had patent ductus arteriosus,abdominal CT showed pancreatic steatosis,and X-ray films of both femurs showed a slight widening of the right hip joint space.Both cases were diagnosed by SBDS gene detection.Case one was c.183_184delinsCT and c.258+2T>C compound heterozygous mutation.Case two was c.183_184delinsCT heterozygous mutation and c.258+2T>C homozygous mutation.The treatment mainly included trypsin replacement therapy and nutritional support therapy.After treatment,both children increased in height and weight steadily,and the neutrophil count was monitored to remain stable.With"Shwachman-Diamond"and"SBDS"as the keywords,the literature was consulted and reviewed,and fewer patient with liver damage were reported to have liver damage,and the first manifestations were mostly growth retardation,blood routine abnormalities and steatic diarrhea.Conclusions The common clinical manifestations of children with SDS are pancreatic steatosis and exocrine insufficiency,at least one line the decrease in peripheral blood,especially neutrophil count reduction and skeletal abnormalities.Some children have hidden onset due to abnormal liver function.It is necessary to improve the understanding of the disease,and SBDS gene testing is helpful for diagnosis.