Objective: To study the premanifest stage of the most common SCAs. Specifically, we wanted to determine the conversion rate to ataxia in risk persons and to determine the sensitivity of different assessment instruments to detect disease manifestation and progression before onset of ataxia.

Background: Spinocerebellar ataxias (SCAs) are fully penetrant autosomal dominantly inherited progressive ataxia disorders. At risk individuals for SCAs provide a unique research opportunity to prospectively study the premanifest disease phase.

Method: The prospective study of individuals at risk for spinocerebellar ataxia type 1,2,3 and 6 (RISCA) is a multinational, longitudinal observational study.[1] 302 non-ataxic (SARA score <3) adult individuals that descended from a SCA patient (offspring and sibs) were included at 14 European study centres. Anonymous genetic tests were done in all study participants. Follow-up assessments were done in 2-year intervals. Outcome parameters were SARA, INAS, SCAFI and CCFS. In this interim analysis, we included 83 SCA1, 45 SCA3, and 22 SCA6 at risk individuals who had at least one follow-up.

Results: During the observational period of maximally 9.4 years (mean 4.4 ± 2.2), 51% of SCA1, 42% of SCA3, and 13% of SCA6 mutation carriers converted to manifest ataxia. In SCA1 carriers, SARA, INAS, SCAFI and CCFS progression, in SCA3, SARA progression differed from those of non-carriers. None of the parameters significantly changed in non-converters of any genotype.

Conclusion: Our study for the first time determined the conversion rate of SCA mutation carriers to manifest ataxia. The findings in non-converters show that the available clinical outcome parameters lack sensitivity in the premanifest phase.

References: [1] Jacobi H, Reetz K, du Montcel ST et al.. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol. 2013 Jul;12(7):650-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evolution-of-ataxia-in-risk-persons-for-spinocerebellar-ataxia-sca/