Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic...

To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy.

Five symptomatic and nine asymptomatic at-risk members of the kindred.

Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy.

Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symptoms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology.

This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown.