X-Linked Agammaglobulinemia with De novo BTK Mutations in Chinese Children: A Case Report and Literature Review

X-linked agammaglobulinemia (XLA) is a rare primary immunodeficiency caused by Bruton’s tyrosine kinase ( BTK ) mutations that lead to defective B-cell development and severe antibody deficiency. This study aimed to describe a novel de novo BTK mutation in a Chinese child and summarize the clinical and genetic features of reported Chinese cases with de novo BTK mutations. A Chinese boy with recurrent severe infections and profound hypogammaglobulinemia was evaluated using whole-exome sequencing and Sanger sequencing for BTK gene analysis. Clinical, immunological, and follow-up data were collected. In addition, a literature review of reported Chinese XLA cases with de novo BTK mutations was performed to assess the clinical manifestations, immunological profiles, and mutation spectrum. We identified a novel de novo frameshift BTK mutation (c.1912_1913insCAGAT, p.Glu640Glnfs*10) that was predicted to disrupt the tyrosine kinase domain. The patient responded well to immunoglobulin replacement therapy, with no severe infections during the 4-year follow-up period. A literature review identified 30 additional Chinese patients with de novo BTK mutations, most commonly presenting with recurrent respiratory infections in nearly all cases and markedly reduced CD19 + B cells (< 2% in 28/29 patients with available data). The mutations were heterogeneous but clustered within the tyrosine kinase domain. This study expands the BTK mutation spectrum by reporting a novel de novo mutation and highlights the clinical heterogeneity of XLA in Chinese patients. Early molecular diagnosis is critical for timely IVIG therapy, improved outcomes, and informed genetic counseling, even in sporadic cases without a family history.