Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy

We evaluated the autonomic control of the cardiovascular system and the skin innervation of a patient from a new Italian family with a genetically proven diagnosis of adult-onset autosomal dominant leukodystrophy (ADLD) due to lamin B1 gene duplication. Cardiovascular reflexes and pharmacological assessment indicated a selective sympathetic failure, sparing cardiovagal function. Microneurography revealed absent sympathetic activity. The evaluation of autonomic innervation of skin annexes showed severely depleted and morphologically abnormal noradrenergic dopamine-β-hydroxylase (DβH) immunoreactive fibres with preserved cholinergic vasoactive intestinal polypeptide (VIP) immunoreactive fibres. This peculiar autonomic dysfunction may represent a hallmark for ADLD.