A Case Report of X-Linked Hyper-IgM Syndrome Associated with the CD40LG Variant: Successful Management with Immunoglobulin G Replacement Therapy
Abstract
Background: X-linked hyper-IgM syndrome (X-HIGM) is a rare primary immunodeficiency disorder characterized by recurrent infections, hypogammaglobulinemia, and elevated IgM levels. The condition results from mutations in the CD40LG gene, which encodes CD40 ligand, a protein essential for B cell activation and immunoglobulin class switching. This study presents a clinical case of X-HIGM in a young child and highlights the effectiveness of immunoglobulin G replacement therapy in managing the disease.
Methods: Whole-exome sequencing and Sanger sequencing were performed to identify the genetic cause of the patient’s recurrent infections. A hemizygous c.409+1_409+19del mutation was identified in the CD40LG gene, confirming the diagnosis of X-HIGM. Immunoglobulin G replacement therapy was administered to manage the patient’s condition.
Result: Peripheral immunoglobulins confirmed the clinical observations, with low IgG and A but strikingly high IgM levels. Recurrent otitis media and pneumonia were common in early childhood. The genetic testing performed afterward confirmed that the mutation was present in the two affected siblings. This favorable clinical response with a decrease in the frequency of infections and the stability of the IgG levels over the time suggests that IgRT may have a long-term effective role in the management of a rare primary immunodeficiency. It also stresses the need for genetic workup for diagnosis, family counselling, and management of rare immunodeficiency syndromes.
Conclusion: This case highlights the need for early diagnosis and treatment of X-HIGM. IgG replacement therapy is an effective option when stem cell transplantation is not possible or suitable.
Keywords:
Hyper-IgM syndrome, Primary immunodeficiency, Young children, Immunoglobulin G replacement therapy, CD40LGFull Text:
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DOI: https://doi.org/10.62940/als.v13i1.3880
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