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Case Reports
. 2019 Aug:65:91-96.
doi: 10.1016/j.parkreldis.2019.05.001. Epub 2019 May 14.

Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families

Giovanna De Michele  1 , Maria Lieto  1 , Daniele Galatolo  2 , Elena Salvatore  1 , Sirio Cocozza  3 , Melissa Barghigiani  2 , Alessandra Tessa  2 , Jacopo Baldacci  2 , Sabina Pappatà  4 , Alessandro Filla  1 , Giuseppe De Michele  5 , Filippo M Santorelli  2
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Case Reports

Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families

Giovanna De Michele et al. Parkinsonism Relat Disord. 2019 Aug.

Abstract

Introduction: Spinocerebellar ataxia 48 has recently been described as an adult onset ataxia associated with a cerebellar cognitive affective syndrome, caused by a heterozygous mutation in the STUB1 gene.

Methods: We characterized the clinical and neuroimaging phenotype of eight patients from two autosomal dominant ataxia multigenerational Italian families, in whom we conducted whole exome sequencing, targeted multigene sequencing, and Sanger sequencing studies.

Results: We describe a complex syndrome characterized by ataxia and cognitive-psychiatric disorder in all cases, variably associated with chorea, parkinsonism, dystonia, urinary symptoms, and epilepsy. MRI showed a significant cerebellar atrophy, coupled to a T2-weighted hyperintensity affecting the dentate nuclei and extending to the middle cerebellar peduncles, whereas FDG-PET studies revealed glucose hypometabolism in cerebellum, striatum, and cerebral cortex. We identified two different novel STUB1 mutations segregating in the two families. One of the two mutations, p.(Gly33Ser), occurs in the TRP domain, whereas p.(Pro228Ser) is located in the ubiquitin ligase region.

Discussion: We emphasize the similarity of the described clinical picture with that of SCAR16, an autosomal recessive ataxia caused by biallelic mutations in the same gene, and of spinocerebellar ataxia type 17, which is considered the main Huntington's disease-like syndrome. The pathogenesis of the disease and the relationship between SCA48 and SCAR16 remain to be clarified.

Keywords: Ataxia; CHIP; Dominant; HD-Like; SCA48; STUB1.

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