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http://crossmark.crossref.org/dialog/?doi=10.1007/s12311-015-0749-6&domain=pdf
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Web End = Cerebellum (2016) 15:829831
DOI 10.1007/s12311-015-0749-6
SHORT REPORT
Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (POLG) Mutation
Nicolas Nicastro1 & Emmanuelle Ranza2 &
Stylianos E. Antonarakis2,3,4 & Judit Horvath1
Published online: 25 November 2015# Springer Science+Business Media New York 2015
Abstract Progressive ataxia with palatal tremor (PAPT) is a syndrome caused by cerebellar and brainstem lesions involving the dentato-rubro-olivary tract and associated with hypertrophic olivary degeneration. Etiologies include acquired posterior fossa lesions (e.g. tumors, superficial siderosis, and inflammatory diseases) and genetic disorders, such as glial fibrillary acidic protein (GFAP) and polymerase gamma (POLG) mutations. We describe the case of a 52-year-old man who developed pure progressive ataxia and palatal tremor. Genetic analysis has shown that he is compound heterozygote for a known pathogenic (W748S) and a novel POLG variant (I1185N). Patients with POLG recessive mutations usually manifest a more complex clinical picture, including polyneuropathy and epilepsy; our case emphasizes the
need to consider a genetic origin in a seemingly sporadic and pure PAPT.
Keywords Ataxia . Cerebellar disorders . Mitochondrial disorders . Polymerase gamma
Introduction
Progressive ataxia with palatal tremor (PAPT) is caused by cerebellar and brainstem lesions involving the dentatorubro-olivary tract, also referred to as Guillain-Mollaret triangle, resulting in characteristic hypertrophic olivary degeneration. Etiologies include acquired posterior fossa lesions (such as tumors, superficial siderosis, and inflammatory diseases) and genetic disorders [1]. Cases have been described with pathogenic variants in GFAP (OMIM 137780, adult-onset Alexanders disease), in SURF1 (OMIM 185620), and polymerase gamma (POLG) (OMIM 174763). When linked to these latter genes, PAPT is usually part of a wider clinical picture, including extensive neurological symptoms and/or hepatic abnormalities, which are due to mitochondrial dysfunction [2, 3].
Case Report
A 52-year-old male patient, treated for hypertension and diabetes, presented to our neurology division in 2013 because of progressive gait and balance difficulties since two years. One year later, he started complaining of audible ear click and oscillopsia. On neurological examination, he had pendular vertical nystagmus, dysarthria, kinetic and static ataxia with severe postural instability, as well as palatal tremor (as shown
Nicolas Nicastro and Emmanuelle Ranza contributed equally to this work.
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s12311-015-0749-6
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