Leukodystrophies are genetic, neurodegenerative white matter diseases of the central nervous system (CNS) caused by mutations in various genes, presenting with heterogeneous clinical features and age of onset. It is well established that some leukodystrophies have peripheral nervous system (PNS) involvement, whether demyelinating, axonal or mixed in pathology. However, the prevalence of peripheral neuropathy in adult leukodystrophies is unknown. Early recognition of PNS involvement in these disorders is imperative to enable appropriate management and care of the symptoms. 

We performed a retrospective review of all adult subjects followed at our two institutions for white matter disease of genetic origin to select patients with evidence of PNS involvement as documented by nerve conduction studies (NCS) and/or electromyography (EMG)For these subjects we collected and analyzed data on sociodemographic status, family history, clinical characteristics, and disease course, nerve conduction studies (NCS), electromyography (EMG), MRI features and genetic testing results.

From our combined cohorts of 161 adult subjects followed for genetic white matter diseases, we identified 14 patients (8.7%) with documented PNS involvement. A definite genetic diagnosis was established in 5 subjects (3 with adult polyglucosan body disease, 1 with metachromatic leukodystrophy, 1 with POLR3-related disorder) while 9 subjects remained undiagnosed despite extensive genetic investigations. The demographic, clinical, radiological, and electrophysiological data will be presented. 

This is the first study conducted to assess the prevalence of peripheral neuropathy in adult patients with leukodystrophy. In our two independent cohorts, PNS involvement is rare, however, early recognition of the concurrence of CNS and PNS involvement is essential to plan appropriate management of the patients’ symptomatic care and is key as more treatment options are becoming available.