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