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. 2016 Jul:28:80-6.
doi: 10.1016/j.parkreldis.2016.04.030. Epub 2016 Apr 27.

Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38)

Barbara Borroni  1 , Eleonora Di Gregorio  2 , Laura Orsi  3 , Giovanna Vaula  3 , Chiara Costanzi  4 , Filippo Tempia  5 , Nico Mitro  6 , Donatella Caruso  6 , Marta Manes  7 , Lorenzo Pinessi  3 , Alessandro Padovani  7 , Alfredo Brusco  2 , Loredana Boccone  8
Affiliations

Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38)

Barbara Borroni et al. Parkinsonism Relat Disord. 2016 Jul.

Abstract

Introduction: SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified.

Objective: The present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38.

Methods: We extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian families. All had the ELOVL5 c.689G > T (p.Gly230Val) missense mutation.

Results: Age at disease onset was in the fourth decade of life. The presenting features were nystagmus (100% of cases) and slowly progressive gait ataxia (95%). Frequent signs and symptoms included pes cavus (82%) and hyposmia (76%); rarer symptoms were hearing loss (33%) and anxiety disorder (33%). The disease progressed with cerebellar symptoms such as limb ataxia, dysarthria, dysphagia, and ophtalmoparesis followed in the later stages by ophtalmoplegia. Peripheral nervous system involvement was present in the last phase of disease with sensory loss. Dementia or extrapyramidal signs were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented cerebellar atrophy with sparing of cerebral cortex and no white matter disease.

Conclusions: SCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions.

Keywords: Ataxia; ELOVL5; Gene; Mutation; SCA38.

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Figures

Fig. 1
Fig. 1
Pedigrees of the three Italian families with SCA38. Unfilled symbols indicate unaffected family members, and solid black symbols affected members. A line above the symbol indicates individuals for whom DNA was available. The genotype of the ELOVL5 mutations is indicated below each tested subject. Individuals carrying ELOVL5 mutation are indicated by a “±” below the symbol.
Fig. 2
Fig. 2
Signs and symptoms (panel A) and loss of activities of daily living (panel B) of SCA38 patients according to decades from disease onset. In grey, symptoms reported in the first 10 years of the disease, in blue those reported from 10 to 20 years of the disease, in violet those reported over 20 years from the onset of symptoms. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3
Structural and functional neuroimaging findings in two patients with SCA38 (SCA38-01-BS III:10 and SCA38-01-BS III:6). Panel A. Coronal, sagittal and axial magnetic resonance imaging sections (MRI). Panel B. FDG-PET images were processed by Statistical Parametric Mapping (SPM8), and single-subject analysis using a group of 19 healthy controls (mean age: 53 years; female: 59%) was performed (patient < controls) and results were superimposed to T1 MRI template. Statistical threshold was set at P < 0.001, uncorrected for multiple comparisons, with voxel threshold = 100 voxels.
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References

    1. Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol. 2010;9:885–894. - PubMed
    1. Schöls L., Bauer P., Schmidt T., Schulte T., Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291–304. - PubMed
    1. Globas C., du Montcel S.T., Baliko L., Boesch S., Depondt C., DiDonato S., Durr A., Filla A., Klockgether T., Mariotti C., Melegh B., Rakowicz M., Ribai P., Rola R., Schmitz-Hubsch T., Szymanski S., Timmann D., Van de Warrenburg B.P., Bauer P., Schols L. Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov. Disord. 2008;23:2232–2238. - PubMed
    1. Yamada M., Sato T., Tsuji S., Takahashi H. CAG repeat disorder models and human neuropathology: similarities and differences. Acta Neuropathol. 2008;115:71–86. - PubMed
    1. Rossi M., Perez-Lloret S., Doldan L., Cerquetti D., Balej J., Millar Vernetti P., Hawkes H., Cammarota A., Merello M. Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur. J. Neurol. 2014;21:607–615. - PubMed