Pol III-Related Leukodystrophies: Dystonia as a New Clinical Feature (P05.137)

Objective: This study reports dystonia as a new clinical feature for the recently described Pol III-related leukodystrophies. Background Leukodystrophies refer to a heterogeneous group of progressive neurodegenerative disorders characterized by abnormal central nervous system white matter on brain imaging. There currently exists over 20 subtypes of leukodystrophies, the majority of which have a known specific genetic defect. Recently, recessive mutations in POLR3A and POLR3B encoding for the two largest subunits of RNA polymerase III (Pol III) were found to be responsible for three clinically different, but overlapping leukodystrophy phenotypes: Tremor-Ataxia with Central Hypomyelination (TACH), Leukodystrophy with Oligodontia (LO), and 4H syndrome (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism syndrome). Here, we present a new clinical feature of Pol III-related leukodystrophies: dystonia. Design/Methods: We have reviewed the medical charts of 18 mutation-proven Pol III-related leukodystrophy cases: seven TACH and eleven 4H. Results: Dystonia, of varying degree, was found to be a clinical feature in 4 cases: two TACH and two 4H. Conclusions: This is the first report describing dystonia as a clinical feature in Pol III-related leukodystrophies. Better clinical characterization of these rare disorders will help lead to an earlier and more precise diagnosis in affected patients. Disclosure: Dr. Osterman has nothing to disclose. Dr. Orcesi has nothing to disclose. Dr. Sylvain has nothing to disclose. Dr. Sebire has nothing to disclose. Dr. Melancon has nothing to disclose. Dr. Chouinard has received personal compensation for activities with Teva Neuroscience, Novartis, Shires, and Prestwick. Dr. Chouinard has received personal compensation in an editorial capacity from Novartis. Dr. Chouinard has received research support from Novartis, Teva Neuroscience, Elan Corporation, Schering-Plough Corporation, Merck & Co., Inc., Kyowa, and Amarin. Dr. Vanderver has nothing to disclose. Dr. Bernard has received personal compensation for activities with Actelion Pharmaceuticals Canada Inc, Santhera, Venture in Research as a participant on advisory boards and research teams.