Neurodegenerative Complications in XLA

Introduction X-linked agammaglobulinemia (XLA) is commonly associated to central nervous system (CNS) infections; however, the incidence of neurodegenerative disease without a known pathogen remains unknown, with only 15 cases reported to date. Presentation A male patient was diagnosed with XLA at the age of 4 after having pneumonia and meningitis and was started on immunoglobulin therapy (IVIG). At 17, he received anti-tuberculosis therapy for lung tuberculosis. At 25, he developed gait instability and hearing loss. MRI revealed extensive cerebellar atrophy resembling multisystem atrophy type C. Infectious causes were ruled out through comprehensive cerebrospinal fluid (CSF) and blood analysis. He was started on a high-dose IVIG (1 g/kg every 2 weeks) alongside selegiline, amantadine sulphate, pregabalin, vitamin E, B3, and zinc. Over the next 4 years, there was mild neurocognitive improvement, with stable MRI findings. IVIG was reduced to 0.6 g/kg every 3 weeks. Several months after, a slight neuropsychological deterioration was observed but was attributed to psychological trauma of losing a family member. A year later, regardless of high trough IgG levels (12.7 g/L), he was hospitalized due to bilateral pneumonia caused by Haemophilus influenzae and was treated with ceftriaxone and azithromycin with a favorable effect. IVIG was again increased to 1 g/kg every 2 weeks, resulting in clinical stability, no severe infections, and stable MRI findings during the next 2-year period in now a 32-year-old patient, although slight neurocognitive and motor decline persisted. Discussion This case highlights the complexity of managing neurodegenerative complications in XLA, a rare and poorly understood manifestation with no established treatment protocol. High-dose IVIG provided some improvement, but progressive neurocognitive decline appears to be inevitable.