Clinical And Genetic Diagnosis Of 11 Patients With Severe Combined Immunodeficiency

Objective:The aim of this study is to analyze the clinical, laboratory and molecular characteristics of 11 patients with severe combined immunodeficiency (SCID). Futhermore, explore the possible relationship between genotype and phenotype. And to provide detailed information for early diagnosis and effective treatment.Methods:Patients with suspected SCID admitted to Children’s hospital of Chonqing Medical University during May 2014 and March 2015 were included in this study. Their clinical and laboratory data were evaluated. Blood samples were collected from patients and relatives. The levels of T cell recepator rearrangement excision circles(TRECs) were detected by Qunantitative Real-time PCR.IL2RG gene and RAG1/RAG2 gene were directly sequenced respectively based on the possible diagnosis. The IL2RG gene were analyzed by polymerase chain reaction (PCR) directed sequencing in the amniotic fluid cells of two fetus whose mother were mutant IL2RG gene carriers.Results:Six patients and one fetus were diagnozed as X linked severe combined immunodeficiency, while 5 patients were classified as T-B-SCID caused by RAG gene mutations (RAG1/RAG2:4/1).Besides the two fetus, the mean age of onset of the six patients with IL2RG gene mutation and five patients with RAG1/RAG2 gene mutation were 101±62 and 62±32 days respectively, and the mean age of death were 159±89 and 123±23 days respectively. The clinical diagnosis were delayed 1 month.In addition to previously reported mutations, Five novel mutations were found in RAG gene (RAG1:c.1528G>T, c.2765-2766delCT, c.3072-3073insT, c.2005G>A; RAG2:c.1278-1279insGGAT).The pathogens were identified in six cases of all the eleven patients, and high-efficient beta-lactam antibiotics were widely used in all the patients. Intravenous immune globulin(IVIG) were used in each patients with a dose of lg/kg.Conclusion:IL2RG is the most common cause of severe combined immunodeficiency, while RAG1/RAG2 are common in T-B-NK+SCID. With the development of diagnosis and treatment of SCID in primary hospital, the SCID patients admitted in our hospital were complicated than the past. Most patients with IL2RG and RAG1/RAG2 gene mutations present with typical clinical presentation. The most effective treatment of affected patients is hematopoietic stem cell transplantation(HSCT) or gene therapy,without reconstruction of immunity system, people usually died in 1 years. Therefore, early diagnosis and effective treatment is important for the prognosis of SCID patients. TRECs testing of newborn is benefit for the early diagnosis of SCID. While prenatal diagnosis in pregnant women with a definitive family history can avoid the birth of babies with SCID.