X-Linked Lymphoproliferative Syndrome in a Kenyan Child with Bronchiectasis

Background X-linked lymphoproliferative syndrome (XLP) is a rare genetic condition characterized by immune dysregulation, clinically manifesting as either an abnormal immune reaction to Epstein-Barr virus infection causing hemophagocytic lymphohistiocytosis (HLH), lymphoproliferative disorders, and/or hypogammaglobulinemia with recurrent infections. There are two subtypes, XLP1, due to mutations in the SH2D1A gene, and XLP2, due to mutations in the XIAP gene. Mutations in SH2D1A lead to deficiency in signaling lymphocyte activation molecule-associated protein, which is involved in intracellular signaling and activation of T cells and T-dependent B cell activation. Case Report We present an 11-year-old Kenyan boy with a history of recurrent pneumonia, otitis media, chronic rhinosinusitis, and cor pulmonale who was being evaluated for primary ciliary dyskinesia (PCD) given the phenotypic features consistent with this diagnosis. Targeted panel genetic testing for PCD, primary immunodeficiencies, and cystic fibrosis (CF) identified a pathogenic mutation in the SH2D1A gene (c.245dup [p.Asn82Lysfs*22]), confirming his XLP diagnosis. Immunological testing identified hypogammaglobulinemia. Although he had elevated ferritin and CRP levels during his hospitalization, he did not meet HLH criteria, and these levels normalized following antibiotic therapy. Chest computed tomography revealed bilateral patchy opacities, left-sided thick-walled cavitation, worsening bronchiectasis, and dilated pulmonary arteries in comparison to similar imaging done two years prior. Echocardiography confirmed pulmonary hypertension. He was initiated on monthly intravenous immunoglobulin replacement and treatment for pulmonary hypertension. We managed his acute bronchiectasis exacerbation and implemented preventive measures including prophylactic microbial agents and continued daily airway clearance. He is scheduled for multidisciplinary follow-up and potential for hematopoietic stem cell transplantation. Discussion Inborn errors of immunity often present with recurrent sinopulmonary infections and bronchiectasis. The clinical features overlap with other diagnoses such as PCD and CF. A multidisciplinary team approach is crucial for an optimal outcome in patients with inborn errors of immunity and multiple comorbidities.