Objective: To broaden diagnostic testing of likely genetic ataxias.

Background: Spinocerebellar ataxia (SCA) refers to a heterogeneous group of degenerative genetic disorders which encompasses a broad clinical and semiological concept, being cerebellar ataxia, pyramidal signs, retinopathy and neuropathy the most common findings. SCA35 is caused by a missense autosomal dominant mutation in the TGM6 gene, responsible for encoding transglutaminase 6, which accumulates in insoluble perinuclear deposits.

To date, some 30 SCA35 cases have been described worldwide, being the onset during adulthood, mainly in Han-Chinese families. It is characterized by proggresive gait imbalance  and mild dysarthria, among pyramidal or propiceptive signs. No cognitive impairment has been described so far.

Method: We report a case whose diagnosis and follow-up is currently carried out by our Neurology Department.

Results:
A 47-year-old woman, with no medical history of interest, consulted for gait and balance disorder, which had started during childhood. Neurological exploration revealed spastic tetraparesis, mainly focused on lower limbs, with severe unsteadiness in standing position. Interestingly, the only cerebellar sign we have found is longstanding scanning speech. 

Lipid and copper metabolism, autoimmunity, paraneoplastic profiles, along with neurotropic virus serology  were normal. MRI only revealed light frontal atrophy and cervical facet arthropathy. Electrophysiological testing showed a nonspecific denervation pattern. 

Genetic testing profiled finally resulted positive for missense mutation in TGM6 gene. Therefore, along with all the previous data, we came to conclude the SCA35 as the definite diagnosis. Patient treatment has been mainly focused on spasticity and gait management.

Conclusion: Differential diagnosis in spastic paraparesis must include TGM6 genetic screening regardless disease onset. To our knowledge, this is the first proven SCA35 case published in the Spanish population.

References: 1. Tripathy, D. et al. Mutations in TGM6 induce the unfolded protein response in SCA35. Hum. Mol. Genet. (2017); 26: 3749–3762.
2. Manini, A., Bocci, T., Migazzi, A. et al. A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation. BMC Neurol. (2020); 408.
3. Klockgether, T., Mariotti, C. & Paulson, H.L. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019; 5(24).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-case-report-of-early-onset-spinocerebellar-ataxia-type-35/