Novel Features and Abnormal Pattern of Cerebral Glucose Metabolism in Spinocerebellar Ataxia 19

Martin Paucar,Peter Gustavsson,Irina Savitcheva,Åsa Bergendal,Magnus Nordenskjöld,Per Svenningsson,José Laffita-Mesa

doi:10.1007/s12311-018-0927-4

Martin Paucar, Peter Gustavsson + Show 5 more

Open Access

https://doi.org/10.1007/s12311-018-0927-4

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Abstract

Spinocerebellar ataxia type 19 (SCA19), allelic with spinocerebellar ataxia type 22 (SCA22), is a rare syndrome caused by mutations in the KCND3 gene which encodes the potassium channel Kv4.3. Only 18 SCA19/22 families and sporadic cases of different ethnic backgrounds have been previously reported. As in other SCAs, the SCA19/22 phenotype is variable and usually consists of adult-onset slowly progressive ataxia and cognitive impairment; myoclonus and seizures; mild Parkinsonism occurs in some cases. Here we describe a Swedish SCA19/22 family spanning five generations and harboring the T377M mutation in KCND3. For the first time for this disease, 18F-fluorodeoxyglucose PET was assessed revealing widespread brain hypometabolism. In addition, we identified white matter abnormalities and found unusual features for SCA19/22 including early age of onset and fast rate of progression in the late course of disease in the oldest patient of this family.

Highlights

Spinocerebellar ataxias (SCA) are a heterogeneous and growing group of autosomal dominant diseases enumerated in chronological order from SCA1 to SCA43 according to the current
Age of onset was not possible to determine in the index case (IV:1) who is 45 years old
The index case was not affected by any other comorbidity usually associated with white matter hyperintensities (WMH), suggesting that these abnormalities may be an underlying feature of Spinocerebellar ataxia type 19 (SCA19)/22

Summary

Introduction

Spinocerebellar ataxias (SCA) are a heterogeneous and growing group of autosomal dominant diseases enumerated in chronological order from SCA1 to SCA43 according to the current. The Thr377Met (T377M) mutation in KCND3 has been described only once in a Japanese patient affected by pure cerebellar ataxia [7]. The aim of this study was to perform a comprehensive characterization of four affected members of a Swedish family spanning five generations; all affected family members harbor the T377M mutation in KCND3. This characterization includes clinical and cognitive evaluations, structural brain imaging and, for the first time for this disease, brain 18Ffluorodeoxyglucose PET ([18F] FDG PET)

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