Title : A Libyan patient with POLR3B-related leukodystrophy: A rare adult-onset case report
Abstract:
Leukodystrophies are a heterogeneous group of rare genetic disorders characterized by abnormalities in central nervous system white matter, leading to progressive neurological dysfunction. Among these, POLR3B-related leukodystrophy represents a particularly rare and underrecognized subtype, especially in adult-onset presentations. The disease is caused by pathogenic variants in the POLR3B gene, which encodes a critical subunit of RNA polymerase III, essential for normal myelin development and maintenance.
This presentation reports and analyzes the case of a 19-year-old Libyan male who presented with a two-year history of progressive neurological deterioration, primarily manifesting as gait ataxia, tremor, dysarthria, visual disturbances, and impaired coordination. The clinical course was complicated by diagnostic uncertainty, initially raising suspicion for post-infectious autoimmune encephalitis following a prior COVID-19 infection. Despite extensive investigations and immunomodulatory therapy with intravenous immunoglobulins, the patient showed no clinical improvement.
Brain magnetic resonance imaging revealed diffuse hypomyelinating white matter changes involving the parieto-occipital regions, corpus callosum, corticospinal tracts, cerebellar peduncles, and cerebellar hemispheres—findings consistent with hypomyelinating leukodystrophy. Definitive diagnosis was achieved through genetic testing, which identified heterozygous pathogenic variants in the POLR3B gene. This case represents the first reported instance of POLR3B-related leukodystrophy in Libya, contributing valuable data to the limited global literature on adult-onset presentations.
The case highlights the significant phenotypic variability of POLR3-related disorders and emphasizes the diagnostic challenges faced when rare genetic diseases present beyond childhood. It underscores the importance of considering inherited leukodystrophies in the differential diagnosis of young adults with progressive ataxia and white matter abnormalities. Although no disease-modifying therapy currently exists, early recognition remains crucial for appropriate counseling, supportive management, and future therapeutic trials. This report aims to increase awareness of adult-onset POLR3B-related leukodystrophy and advocate for the integration of genetic testing into neurological diagnostic pathways.
