Leukoencephalopathy in adults: Is it adrenoleukodystrophy? A case report and molecular analysis

Adult onset cerebral X-ALD (AOCALD) is a rare disease, but should be considered an important differential diagnosis in adults presenting with leukencephalopathy. We here report the case of a 40-year-old man with a history of progressive cognitive decline who presented with a first-time seizure. Initial workup included magnetic resonance imaging (MRI) of the brain which showed extensive frontotemporal leukoencephalopathy. A subsequent brain biopsy showed demyelination and perivascular macrophages. Further workup included serum very long chain fatty acid concentration (VLCFA), which was found to be elevated. An MRI of the total spine showed diffuse atrophy, but no intrinsic cord signal changes, and the diagnosis of AOCALD was established. Genomic sequencing revealed a nonsense mutation in exon 8 (2188G→A, W601X), to our knowledge not reported in context with AOCALD. A family pedigree was obtained, and other family members at risk were identified and underwent genetic counseling. In conclusion, AOCALD is an important differential diagnosis in adults presenting with cognitive decline. While treatment for affected patients is often supportive only, molecular diagnosis serves as a basis for genetic counseling, identification of relatives at risk and timely referral to a treatment program.