Atypical SCID with RAG2 Mutation: A New Case Report

Introduction RAG1 and RAG2 proteins initiate the V(D)J recombination process, enabling the generation of T and B lymphocytes with a diverse repertoire of antigen-specific receptors. Various mutations in the RAG1 and RAG2 genes are implicated in severe combined immunodeficiency (SCID) with variable phenotypic presentations. Methods Analysis of clinical and laboratory data and treatment of a child diagnosed with RAG2 deficiency. Results A 6-year-old boy, with a family history of a deceased sister at the age of five, was referred to our department for recurrent respiratory infection. He had bilateral subcortical fibrosis with persistent primary vitreous in the right eye. Physical examination revealed facial dysmorphism, depigmented skin lesions, hepatomegaly, and abdominal collateral venous circulation. The patient had anicteric cholestasis with elevated gamma-GT (216 U/L) and liver cytolysis. He was treated with ursodeoxycholic acid and vitamin supplementation, leading to the resolution of liver cytolysis and decreased gamma-GT levels. A biliary MRI suggested early-stage sclerosing cholangitis. Thoracic CT scan showed alveolar consolidations in the lingular and anterobasal segments of the left lower lobe, without bronchial dilatation. Immunoglobulin levels were as follows: IgA <0.2 g/L, IgG 3.04 g/L, and IgM 1.00 g/L. CD markers revealed CD3: 19.5%, CD4: 6%, CD8: 13%, total T cells: 6%, B cells: <0.5%, and NK cells: 78%. Lymphocyte proliferation was reduced in response to both antigens and mitogens. Genetic analysis identified a mutation in the RAG2 gene. The patient experienced recurrent pulmonary and gastrointestinal infections despite regular intravenous immunoglobulin therapy and prophylaxis with itraconazole, cotrimoxazole, and acyclovir. He is currently undergoing preparation for haploidentical stem cells transplantation (HSCT). Conclusion RAG2 mutations are the leading cause of T- B- SCID. Certain mutations reduce but do not completely abolish recombination activity, resulting in a milder disease phenotype. Prognosis remains poor in the absence of HSCT.