Clinical, immunological, and molecular characteristics of severe combined immune deficiency in China.

Severe combined immunodeficiency (SCID) is an inborn error of immunity. The clinical and genetic characteristics of SCID remain poorly characterized in China. This study aimed to analyze the clinical, immunological, and molecular features of the largest cohort of SCID patients from a single center in China. This retrospective study was conducted at the Children's Hospital of Fudan University. Patients diagnosed with SCID between January 2013 and May 2025 were enrolled. A total of 148 patients were included. The mean age at disease onset was 10.7 months, while the mean age at diagnosis was 18.9 months. The most common clinical manifestations included pneumonia (95.3%), diarrhea (52.0%), and hepatomegaly (43.9%). Genetic testing was performed in 134 patients, among whom 121 received a genetic diagnosis, yielding a molecular diagnostic rate of 90.3% (121/134). Variants in 12 distinct genes were identified. The most frequently implicated genes were IL2RG (34.7%), RAG1 (22.3%), RAG2 (9.1%), and LIG4 (8.3%). These four genes accounted for 74.4% of the diagnosed cases. Among the 66 patients who underwent hematopoietic stem cell transplantation, the mortality rate was 36.1% (13/36) in the typical SCID group and 41.4% (12/29) in the atypical group. In conclusion, this study reports the largest cohort of SCID patients in China. Our analysis outlines the clinical, immunological, and genetic spectrum of the disease.