X-linked severe combined immunodeficiency complicated by disseminated bacillus Calmette-Guérin disease caused by a novel pathogenic mutation in exon 3 of the IL2RG gene: a case report and literature review

Abstract

X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.

Keywords: X-linked severe combined immunodeficiency; case report; disseminated bacillus Calmette-Guérin disease; interleukin-2 receptor gamma-chain gene; systemic review.

Figure 1

Photograph of a 4-month-old patient with SCID complicated by systemic disseminated BCG disease caused by a novel IL2RG gene mutation. (A) Scattered subcutaneous nodules on the trunk, with ulceration and scabbing visible below the ear and in the upper left abdomen. (B) Scattered rashes and purplish-blue subcutaneous nodules on the lower limbs, with some scabs forming. (C) Unhealed BCG vaccination site with liquid leakage.

Figure 2

Chest computed tomography (CT) and cytological examination. (A) Chest CT lung window. (B) Chest CT mediastinal window showing scattered inflammation in both lungs. (C) Bone marrow specimen demonstrating significant proliferation and activation of bone marrow, with toxic particles and vacuolar degeneration visible in granulocytes. Red blood cells are mainly composed of middle- and late-stage erythrocytes, and no plate-producing megakaryocytes are present. (D) Rash imprint showing approximately 18% of suspected Langerhans tissue cells, with abundant cytoplasm filled with small grayish-purple particles. The nucleoli are circular or irregular in shape, and the cytoplasm is thick and loose.

Figure 3

IL2RG gene mutation detected in the present case. (A) Sanger chromatogram. (B) Schematic diagram of the mutation sites. (C) Schematic diagram of the mutation protein.