Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive leukodystrophy caused by duplication of LMNB1.

We performed a retrospective chart review of all ADLD patients seen at Mayo clinic to summarize our experience.

Of the 8 patients identified, 3 were male. Age at first reported symptom ranged from 33 to 69 years. Of the male patients, the first symptom was erectile dysfunction (2/3) or neurogenic bladder (1/3). Of the 5 female patients, the first symptom was weakness (3/5), bladder dysfunction (1/5) or depression (1/5). Commonly reported features included neurogenic bladder (8/8), fatigue (7/8), sleep issues (4/8: 2/4 insomnia, 2/4 daytime sleepiness), tremor (4/8), anxiety (4/8), and depression (3/8). The disease course was slowly progressive in all.

Family history of leukodystrophy was positive in 6. Seven patients had LMNB1 duplication and one had a 320-kilobase 5q23.2 duplication, including all of LMNB1 and part of MARCH3.

A total of 18 MRI brains were reviewed for 7/8 patients. Age at MRI ranged from 33 to 69 years. All showed symmetric T2W confluent deep cerebral and periventricular white matter hyperintensities along with involvement of the posterior limb of the internal capsule, corpus callosum, corticospinal tract in brain stem, superior and middle cerebellar peduncles. One CT brain was available that showed hypodensities in the corresponding areas.

Seven MRIs of spine from 6 patients showed moderate diffuse atrophy of the spinal cord more pronounced in cervical and thoracic regions.

ADLD is an ultra-rare progressive leukodystrophy with characteristic neuroimaging and clinical findings. Identification of these clinical symptoms and MRI changes can lead to prompt genetic testing and diagnosis.