Objective: To characterize the clinical presentation and disease progression of patients with spinocerebellar ataxia type 35 (SCA35).

Background: Mutations in TGM6 have been identified to cause SCA35. However, the clinical presentation and disease progression have not been well characterized.

Method: We reviewed patients presented with cerebellar ataxia with no attributable treatable or genetic causes except for mutations in TGM6.

Results: Four patients were identified. Case 1: 63-year-old man with onset of balance difficulty in his 40s followed by slurred speech. He has a family history of cerebellar ataxia. He has a TGM6 mutation causing frameshift with a premature stop codon (Leu281Cysfs*10). He has bilateral esotropia, nystagmus on lateral gaze, scanning speech, hyperreflexia, and truncal/appendicular ataxia. His scale for assessment and rating of ataxia (SARA) score was 21 at the initial visit. He showed an improvement for about 1 year after he adopted a gluten-free diet (GFD). Case 2: 65-year-old man with progressively worsening balance and slurred speech since age 64 as well as REM sleep behavior disorder (RBD). He has no family history of ataxia, but he has a nonsense mutation in TGM6 mutation (Arg231X). He has saccadic pursuit, hypometric saccades, hyperreflexia in the arms, neuropathy in the legs, and ataxia in the limbs and trunk. His SARA remained at 10 for 1 year before worsened to 16. He did not respond to riluzole or GFD. Case 3: 20-year-old man with a family history of ataxia. He was asymptomatic initially but developed rapidly progressive ataxia in the next 4 years with gait impairment, dysphagia, titubation, and pseudobulbar affect. His SARA increased from 13 to 29 in the past 18 months. He has a missense mutation in TGM6 (Asn137Ser). He did not respond to GFD, amantadine, or riluzole. Case 4: 55-year-old man with impaired gait, slurred speech, RBD, and erectile dysfunction since age 51. In addition to cerebellar ataxia, he also has bradykinesia, slight rigidity, and reduced left-arm swing. He has no family history of ataxia but has an intronic mutation in TGM6 (c.1337-7C>A), a variance of unknown significance. He reported benefit from GFD before seen once at our clinic. His SARA was 16.5.

Conclusion: SCA35 can present with pure cerebellar ataxia or with additional symptoms, such as RBD and Parkinsonism. Two of our patients responded to GFD. The benefit of GFD remains to be verified.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-characterization-and-disease-progression-in-spinocerebellar-ataxia-type-35-a-case-series/