Objective: We experience the GBA1 gene related YOPD who showed the progressive supranuclear palsy (PSP) phenotype.

Background: Glucocerebrosidase (GBA1) gene mutations are well-known genetic risk factors for monogenic young onset Parkinson’s disease (YOPD) and have a profound impact on the motor and progressive cognitive impairment of the patients.

Method: 42 year-old man visited out-patient clinic for bradykinesia and right thumb tremor. He had no familial history of parkinsonism and any neurological disease. He was evaluated his parkinsonism with MRI, FP-CIT PET and autonomic function test, cognition test. MRI showed mild cortical atrophy however, severe decreased FP-CIT uptake of posterior striatum, both. Orthostatic hypotension of neurogenic type observed and single domain amnestic mild cognitive impairment (MMSE-28, CDR-0.5) was observed.

Results: His parkinsonism progressed rapidly within 3 years and response of levodopa was poor even though increased up to 900mg. UPDRS motor score was 42 and he complained difficulty of stand up, freezing of gait and frequent fall. He showed grimacing face, decreased eye blinking and round the house sign. In the NGS PD gene panel, GBA1 (c.1342G>C) pathogenic variant was observed.

Conclusion: GBA1 gene could influence of a-synuclein and tau pathology both. Because the decreased function of lysosome cause a synuclein aggregation and then it increase the tau protein accumulation. Therefore GBA1 gene associated PSP type shares the phenotype mimicry with YOPD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/young-onset-parkinsons-disease-patient-who-has-gba1-pathogenic-variant-exhibiting-progressive-supranuclear-palsy-phenotype/