LAMB1-related adult-onset leukoencephalopathy presenting with cognitive decline: diagnostic workup and review of the literature

Leukoencephalopathies encompass a heterogeneous group of acquired and genetic white matter disorders with variable clinical presentations. We report a case of adult-onset leukoencephalopathy caused by a heterozygous frameshift LAMB1 deletion in a 65-year-old woman presenting with progressive cognitive decline, mood changes, and migraine. Whole-exome sequencing identified a likely pathogenic variant, enabling a diagnosis after extensive metabolic and genetic workup. This case highlights the importance of considering LAMB1 variants in unexplained adult-onset leukoencephalopathies associated with cognitive decline.