探讨1例Shwachman-Diamond综合征(SDS)继发骨髓增生异常综合征(MDS)的病情演变，及临床和基因学特征。

回顾性分析2020年7月31济宁医学院附属医院儿童血液科收治的1例SDS患儿的临床资料，总结SDS患儿的临床特点及基因学特征，并复习文献，综述其诊治进展。

患儿13岁，出生后2个月出现脂肪泻，身高、体重发育落后，伴有手指过度弯曲，出生后儿童保健随诊及多次体检，血常规均提示三系正常。2019年12月4日患儿因发热就诊，血常规提示三系减低。进一步骨髓穿刺检查提示粒、红、巨系增生减低；骨髓免疫分型显示骨髓原始细胞比例2.70%，CD38表达减弱，表型异常，粒系比例明显减低，以成熟粒细胞为主，红系、单核细胞和淋巴细胞未见异常表达；未予治疗，随后不定期复查血常规均提示三系减低。2020年7月31日，患儿因持续发热和三系细胞减少再次就诊，进一步基因检测提示SBDS基因的两个突变：NM-016038.4：exon2：c.258＋2 T>C剪切位点变异和NM-016038.4：exon2：c.184 A>T无义突变，结合出生后的临床表现，明确诊断为SDS。随后骨髓涂片细胞学检查提示原始细胞占11.50%，结合骨髓流式细胞术检测和骨髓活检及免疫组织化学，考虑继发MDS，TP53基因变异率4.10%。2021年4月11日，患儿接受了无关供者造血干细胞移植治疗，移植后短期内病情有所缓解，但在移植后10个月复发，最终因骨髓全面复发、继发感染和出血导致死亡。

SDS患者应密切监测骨髓情况，明确诊断后需尽早行造血干细胞移植治疗，伴有TP53基因突变提示预后不良。

To investigate the clinical and genetic characteristics of a case of myelodysplastic syndrome(MDS) secondary to Shwachman-Diamond syndrome(SDS).

The clinical data of a child with SDS admitted to the Department of Pediatric Hematology, Affiliated Hospital of Jining Medical University on July 31, 2020 were retrospectively analyzed. The clinical and genetic characteristics of children with SDS were summarized, and the literature was reviewed to generalize the progress in diagnosis and treatment for SDS.

The child was 13 years old and developed steatorrhea 2 months after birth. The child exhibited delayed growth and development in height and weight, with excessive curvature of the fingers. Following child health follow-up and multiple physical examinations, red blood cells, white blood cells, and platelets of blood routine were normal. On December 4, 2019, the patient was treated for fever, and the blood routine showed that red blood cells, white blood cells, and platelets were reduced. Further bone marrow puncture examination showed reduced hyperplasia of granulocytes, red blood cells, and giant cells. Bone marrow immunophenotype showed that the proportion of bone marrow original cells was 2.70%, the expression of CD38 was weakened, and the phenotype was abnormal. The proportion of granulocytes was significantly decreased, mainly composed of mature granulocytes. No abnormal expression was found in erythrocyte, monocyte and lymphocyte. No treatment was given, and subsequent irregular reexamination of blood routine showed that red blood cells, white blood cells, and platelets were reduced. On July 31, 2020, the child was re-admitted due to persistent fever and hemocytopenia, and further genetic testing revealed 2 mutations in the SBDS gene: NM-016038.4: exon2: c. 258+ 2 T>C splice site mutation and NM-016038.4: exon2: c. 184 A>T nonsense mutation. Considering the clinical manifestations since birth, the child was definitely diagnosed with SDS. Subsequent bone marrow smear cytology showed that the blast cells accounted for 11.50%. Combined with bone marrow flow cytometry, bone marrow biopsy and immunohistochemistry, secondary MDS were considered, and the TP53 gene mutation rate was 4.10%. On April 11, 2021, the patient underwent a hematopoietic stem cell transplant from an unrelated donor and experienced a short period of remission. However, the patient relapsed 10 months after transplant and eventually died due to total bone marrow recurrence, secondary infection, and bleeding.

Patients with SDS require close monitoring for bone marrow conditions, and hematopoietic stem cell transplantation should be performed as soon as possible after a definite diagnosis, and TP53 gene mutation indicates poor prognosis.