Hereditary diffuse leukoencephalopathy with spheroids mimicking primary progressive aphasia: report of a Greek case

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult onset leukodystrophy, causally related to mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We report the unique case of a Greek HDLS patient, demonstrating an unusual phenotype, reminiscent of primary progressive aphasia (PPA).

A 63-year-old woman was referred with a 2-year history of deteriorating language and memory deficits, apathy, and two generalized tonic-clonic seizures. Neurological and neuropsychological examination revealed prominent aphasia with a pattern consistent with nonfluent variant of PPA. However, brain MRI disclosed confluent T2 and FLAIR white matter hyperintensities with frontal emphasis, whereas genetic testing corroborated the diagnosis of HDLS.

PPA-like patterns may rarely develop in the context of HDLS. Prompt diagnosis of this leukoencephalopathy is essential, since preliminary data suggest that it could represent a potentially treatable disorder.