Clinical and Neuroradiological Features of Spinocerebellar Ataxia 38 (SCA38) (S30.006)

Objective: To describe clinical features, disease course and neuroimaging hallmarks in a large series of patients affected by spinocerebellar ataxia 38 (SCA38). Background: SCA38 is caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids and which is highly expressed in Purkinje cells. Methods: Subjects belong to three Italian pedigrees. We collected clinical and brain neuroimaging data from 21 SCA38 patients, carriers of the ELOV5 c.689G>T (p.Gly230Val) missense mutation, over more than 20 years of the disease course. Patients were evaluated every year, and we then grouped each available assessment according to the time from disease onset: first decade (0-10 years from disease onset), second decade (11-20 years from disease onset), and third decade and over (over 20 years from disease onset). For each decade, we measured the cumulative incidence of considered symptoms. Structural and functional imaging and electrophysiological examination were also performed. Results: Age at disease onset occurred in the fourth decade of life. The presenting features were nystagmus (100[percnt] of cases) and slowly progressive gait ataxia (95[percnt]). Frequent specific signs and symptoms included pes cavus (82[percnt]) and hyposmia (76[percnt]); hearing loss (33[percnt]) and anxiety disorder (33[percnt]) were rare but suggestive symptoms. During disease course, patients developed limb ataxia, dysarthria, dysphagia, and ophtalmoparesis. Sensory loss and ophtalmoplegia appeared only in later disease stages. Dementia, extrapyramidal syndrome and myoclonus were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented specific damage of cerebellum with sparing of cerebral cortex and no significant white matter disease. Conclusions: SCA38 is a rare form of inherited ataxia with specific clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions. Disclosure: Dr. Borroni has nothing to disclose. Dr. Di Gregorio has nothing to disclose. Dr. Orsi has nothing to disclose. Dr. Vaula has nothing to disclose. Dr. Costanzi has nothing to disclose. Dr. Gazzina has nothing to disclose. Dr. Tempia has nothing to disclose. Dr. Mitro has nothing to disclose. Dr. Caruso has nothing to disclose. Dr. Pinessi has nothing to disclose. Dr. Padovani has nothing to disclose. Dr. Brusco has nothing to disclose. Dr. Boccone has nothing to disclose.