Abstract Details

Title A Pathogenic Heterozygous Mutation Affecting ATP13A2 in Parkinson's Disease

Topic Movement Disorders

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 16-014

Objective The goal of this study is to detail clinical descriptions of two siblings that carry a pathogenic heterozygous mutation affecting ATP13A2 and to highlight its association with increased risk for Parkinson’s disease.

Background Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome, a juvenile-onset form of parkinsonism. This condition is autosomal recessive, requiring biallelic pathogenic mutations for full disease expression. However, recent evidence suggests that heterozygous mutations confer an increased risk for parkionsonism as well. These mutations can cause the abnormal presence of α-synuclein in skin samples, and a skin biopsy will be positive.

Design/Methods Case Study

Results A 69-year-old gentleman presented with gradual memory loss and mild parkinsonism with symptoms that had been present for at least 15 years. He had a prior DAT scan that was mildly positive. After a year, his tremor progressed and a Syn-One biopsy was positive, prompting another DAT scan and genetic testing. He was found have a heterozygous pathogenic deletion affecting ATP13A2, explaining his longstanding symptoms and his positive skin biopsy test. His DAT scan also was positive. He was then started on appropriate medication. This led the patient’s younger sibling, who also had a years long history of tremor and shuffling gait, to be diagnosed with the same mutation and receive treatment.

Conclusions The role of ATP13A2 has been confirmed as the casual mutation in Kufor-Rakeb syndrome. Since that time, heterozygous mutations in ATP13A2 have been identified as a potential risk factor for Parkinson’s disease. As ATP13A2 has been shown to regulate α-synuclein metabolism, it can cause a positive skin biopsy, which can aid in diagnosis of less obvious genetic causes.

Authors/Disclosures
Anna Thomsen, MD PRESENTER	Dr. Thomsen has nothing to disclose.
Lorenzo Malfer, MD	Dr. Malfer has nothing to disclose.
Zhiyv Niu, PhD, FACMG (Mayo Clinic)	Zhiyv Niu has nothing to disclose.
Owen A. Ross, PhD (Mayo Clinic Jacksonville)	Dr. Ross has nothing to disclose.
Emanuela Santoro, Medical student	Miss Santoro has nothing to disclose.
Rodolfo Savica, MD, PhD, FAAN (Mayo Clinic)	The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

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