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

Abstract

BackgroundShwachman-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.ObjectiveTo 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.MethodsData 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.ResultsAmong 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.ConclusionSDS 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.

Keywords

• |shwachman-diamond syndrome|child|sbds gene|gene analysis|treatment outcome