X-linked agammaglobulinemia (XLA) is a rare primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene, resulting in absent B cells and agammaglobulinemia. Although early diagnosis significantly improves survival rates, a large proportion of cases are still diagnosed late, especially those with atypical clinical presentations. Neonatal screening using kappa-deleting recombination excision circles (KREC) is a promising method to detect B cell deficiencies early.
To describe the case of a pediatric patient from Brazil with XLA who presented with an atypical neurological manifestation and to emphasize the role of KREC in the early diagnosis of immunodeficiencies.
This is a case report based on medical record analysis. The case describes a 1-year-old male with a history of live-attenuated vaccination (yellow fever) and no prior significant infections, who presented with ataxia, encephalitis, and progressive neurological deficits. Diagnostic evaluation included immunoglobulin levels, immunophenotyping, genetic analysis, and imaging studies. The treatment consisted of administering intravenous immunoglobulin (IVIg). Informed consent was obtained prior to the preparation of this report.
The patient exhibited agammaglobulinemia and a near-complete absence of B cells (CD19+ 0.1%). A mutation in the BTK gene confirmed the diagnosis. Neurological symptoms, initially suspected to result from infectious encephalitis, were secondary to agammaglobulinemia-related immune dysregulation. The treatment with IVIg led to the resolution of neurological deficits. Retrospective analysis of the case revealed that KREC screening could have facilitated an earlier diagnosis and mitigated the neurological complications observed after receiving the yellow fever vaccine with live attenuated virus.
This case highlights the importance of recognizing atypical presentations of XLA and underscores the critical role of neonatal KREC screening in early diagnosis. The implementation of KREC in newborn screening represents a major advancement in the detection of primary immunodeficiencies in Brazil. Broader adoption of screening programs could transform the clinical course of XLA, allowing for timely interventions, prevention of complications, and improvement of patient outcomes.
