Objective: Here we report a patient with late-onset ataxia-myoclonus syndrome harboring mutations in the ATP13A2 gene.

Background: Mutations in ATP13A2 gene have been causally associated with Kufor-Rakeb syndrome (KRS), an autosomal recessive form of juvenile-onset parkinsonism, neuronal ceroid lipofuscinosis, and recently with complicated forms of hereditary spastic paraplegia (SPG78). Action myoclonus has been reported in a unique case belonging to a pedigree with otherwise typical KRS.

Method: The symptoms started at age 39 with action myoclonus and cerebellar ataxia which rapidly progressed until wheelchair at the age of 44. Pyramidal signs, mildly slow saccades, tongue and perioral muscle twitches and pes cavus were also observed. Acquired causes of ataxia and myoclonus were excluded. No other family members were affected. Pharmacological treatment of the disabling action myoclonus was unsuccessful. (Video).

Results: MRI showed cerebellar and brainstem atrophy. Multigene diagnostic panel by NGS showed predicted pathogenic variants in a compound heterozygous state (c.3135C>A; p.Tyr1045Ter and c.3469A>T; p.Lys1157Ter) in ATP13A2 gene.

Conclusion: Mutations in ATP13A2 can cause late-onset ataxia-action myoclonus syndrome further expanding the clinical and genetic spectrum of ATP13A2-associated disorders.

References: Pietrzak A, Badura-Stronka M, Kangas-Kontio T, Felczak P, Kozubski W, Latos-Bielenska A, Wierzba-Bobrowicz T, Florczak-Wyspianska J. Clinical and ultrastructural findings in an ataxic variant of Kufor-Rakeb syndrome. Folia Neuropathol. 2019;57(3):285-294. doi: 10.5114/fn.2019.88459. PubMed PMID: 31588715. Rohani M, Lang AE, Sina F, Elahi E, Fasano A, Hardy J, Bras J, Alavi A. Action Myoclonus and Seizure in Kufor-Rakeb Syndrome. Mov Disord Clin Pract. 2017 Dec 28;5(2):195-199. doi: 10.1002/mdc3.12570. eCollection 2018 Mar-Apr. PubMed PMID: 30868101; PubMed Central PMCID: PMC6407049.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ataxia-and-action-myoclonus-with-biallelic-mutations-in-atp13a2-gene/