Abstract Details

Title Atypical Case of Prion Disease with D178N-homozygous 129M Genotype

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (2:45 PM-3:45 PM)

Poster/Presentation
Number 002

Objective

This study reports an atypical case of genetic prion disease (gPrD) with a missense mutation in PRNP at codon 178 (D178N) linked with homozygous methionine at codon 129 (129M).

Background gPrD with a mutation in PRNP is a rare condition associated with polymorphism at codon 129. D178N-129M is known to be responsible for fatal familial insomnia (FFI).

Design/Methods Case report.

Results A 58-year-old woman presented with rapidly progressive cognitive decline, abnormal movements, and significant weight loss for four months. The physical examination revealed impaired speech, akathisia in distal extremities, and a parkinsonian gait. Her family history revealed a pattern of rapidly progressive dementia (RPD) among her relatives, of which Creutzfeldt-Jakob disease (CJD) was suspected in one of her sisters. Routine blood tests and CSF analysis showed no abnormalities except mildly elevated CSF t-tau. The CSF real-time quaking-induced conversion assay was negative. Brain imaging revealed subtle cortical ribboning in both anterior cingulate gyrus, insular cortex, and orbitofrontal cortex, which are not typical for PRNP mutation. The overnight EEG suggested a diffuse reduction in brain function with a disruption of the sleep-wake pattern. ¹⁸F-Fluorodeoxyglucose PET brain scan showed multiple hypometabolic areas. Although her clinical phenotype resembled genetic CJD (gCJD), PRNP sequencing revealed D178N associated with homozygous 129M. After 16 months, the patient was fully dependent with frequent myoclonus and insomnia despite multiple supportive medications. In our review of patients with D178N-129M from 32 articles (1993-2023), 11 out of 32 individuals with gCJD phenotypes were confirmed neuropathologically; 63.6% had gCJD and 36.4% had FFI pathology. Whereas 44 out of 144 individuals with FFI phenotypes were confirmed neuropathologically; 97.7% had FFI and 2.3% had gCJD pathology.

Conclusions This case highlights an uncommon presentation of gPrD with D178N-129M mutation in PRNP. Our findings underscore the importance of considering gPrD in patients with a family history of RPD.

Authors/Disclosures
Thanapoom Taweephol, MD (Department of Microbiology, Faculty of Medicine, Chulalongkorn University) PRESENTER	Dr. Taweephol has nothing to disclose.
Thanakit Pongpitakmetha (Department of Pharmacology, Faculty of Medicine, Chulalongkorn University)	Mr. Pongpitakmetha has nothing to disclose.
Pasin Hemachudha, MBBS (King chulalongkorn memorial hospital)	Dr. Hemachudha has nothing to disclose.
Poosanu Thanapornsangsuth (Thai Red Cross Emerging Infectious Diseases - Health Science Centre)	Poosanu Thanapornsangsuth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai.

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