Barzilai University Medical Center

45 Research Day 2020 Barzilai University Medical Center 27 FAMILIAL CREUTZFELDT-JAKOB DISEASE HOMOZYGOUS TO THE E200K MUTATION: CLINICAL CHARACTERISTICS AND DISEASE COURSE Zeev Nitsan 1,2 , Oren S. Cohen 3,5 , Joab Chapman 4,5 , Ester Kahana 1,2 , Ron Milo 1,2 , Michael Osherov 1,2 , Hanna Rosenmann 6 , Shmuel Appel 1,2 1 Department of Neurology, Barzilai University Medical Center, Ashkelon; 2 Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva; 3 Department of Neurology, Assaf Harofeh Medical Center, Zerifin; 4 Department of Neurology, The Sagol Neuroscience Center, and Chaim Sheba Medical Center, Tel-Hashomer; 5 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv; 6 Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Medical Organization, Faculty of Medicine, Hebrew University, Jerusalem Background Most cases of Creutzfeldt-Jacob disease (CJD) in Israel are familial, due to an unusual cluster of the disease among Jews of Libyan origin carrying the E200K mutation in the gene encoding for the prion protein ( PRNP ). The disease is transmitted as an autosomal-dominant trait and is characterized by rapidly-progressive dementia, psychiatric symptoms with behavioral changes, myoclonus, cerebellar, pyramidal and extrapyramidal involvement and visual disturbances, typically leading to death within less than 1 year. Hypothesis fCJD patients homozygous to the mutated gene should have a more severe form and rapid course of the disease. Objective To characterize the demographic, clinical features and disease course of fCJD patients homozygous to the E200K mutation. Methods The Israeli National CJD Database was screened for homozygous E200K patients. Patients' demographic data including gender, age of onset, their clinical presentation, neurological examination, imaging characteristics, EEG and TAU protein levels in CSF were collected. Results Ten homozygous E200K patients were identified (80% men). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3± 7. 7 years (range 42-63) with average disease duration of 27.7± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficit in 2/10 patients. In comparison with 228 heterozygous E200K fCJD patients, homozygous patients were significantly younger at disease onset (47.5 years vs 59.7 years, p<0.001), had longer disease duration (27.7 vs 8.5 months, p<0.001) and presented more frequently with behavioral change (4/10 vs. 34/228, p=0.05). Levels of tau protein in the CSF did not differ between groups. Conclusions Homozygous E200K fCJD is characterized by younger age of onset and, contrary to the hypothesis, longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients.