Objective: Autosomal recessive mutations in ATP13A2 gene is a rare cause of levodopa-responsive parkinsonism with atypical features of supranuclear gaze palsy, spasticity, dystonia, dementia, myoclonus, so called PARK9, Kufor-Rakeb syndrome (KRS). The onset of the clinical manifestation is either juvenile (under the age of 21 years) or young (between the ages of 21 and 40 years) causing juvenile or early-onset parkinsonism. This case-report presents a patient with later-onset Parkinson’ s Disease reponsive to levodopa associated with hetrozygous ATP113A2 gene mutation without other additional features of KRS.

Background: A-51 year old woman presented to our hospital with involuntary movements at her limbs and abnormal turning at her right foot.

Method: She was diagnosed as Parkinson’ s Disease at the age of 48 years with the onset of right hand tremor and slowliness. Her medical history was unremarkable and  family history was negative. She was under low dose of levodopa benzerazid 125 mg po, tid, amantadine po, bid. She had good levodopa response. Neurological examination revealed bilateral bradykinesia and rigidity predominantly affecting right hemibody with peak-dose dysknesias and right foot dystonic posturing.

Results: She had no developmental delay. Her cognition was normal. Laboratory investigations including Wilson’ s disease evaluations were normal. Cranial MRI was unremarkable. Genetical analysis of the patient revealed heterozygous ATP13A2 gene mutations.

Conclusion: Mutations in ATP13A2 are reported as a rare cause of juvenile or early-onset parkinsonism with good  levodopa response accompanied by atypical features charaterized with vertical supranuclear gaze palsy, spasticity, and cognitive decline suggesting a pallido-pyramidal syndrome. Unlike this phenotypic spectrum, this case is presented to emhasize that heterozygous mutations in ATP13A2 gene may also present with a later onset (between the ages of 40 and 50 years) clinical spectrum of typical parkinsonism in which dystonia with low doses of levodopa may be a clue to keep in mind ATP13A2 mutations.

References: 1. Fong CY, Rolfs A, Schwarzbraun T, Clein C, O’ Callaghan FJK. Juvenile parkinsonism associated with heterozygous frameshift ATP13A2 gene mutation. European Journal of Pediatric Neurology 2011;15: 271-275. Doi 10.1016/j.ejpn.2011.01.001.
2. Park JS, Blair NF, Sue CM. The role of ATP13A2 in Parkinson’s disease: Clinical phenotypes and molecular mechanisms. Movement Disorders Journal 2015; doi.org/10.1002/mds.26243.
3.Djarmati A, Hagenah J, Reetz K, Winkler S, Behrens MI, Pawlack H, Lohmann K, Ramirez A, Tadić V, Brüggemann N, Berg D, Siebner HR, Lang AE, Pramstaller PP, Binkofski F, Kostić VS, Volkmann J, Gasser T, Klein C. ATP13A2 variants in early-onset Parkinson’s disease patients and controls. Movement Disorders Journal 2009; 24 (14): 2104-2111. doi.org/10.1002/mds.22728

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-rare-case-of-parkinson-s-disease-associated-with-heterozygous-atp13a2-gene-mutation-what-if-there-are-no-atypical-features-with-a-later-onset/