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.