Objective: To determine if peripheral nerve involvement and the type of TTPA mutation are determinant for gait ataxia in patients with AVED in vitamin E supplementation and normal serum vitamin E.

Background: Ataxia with Vitamin E Deficiency (AVED) is a potentially treatable recessive ataxia and neuropathy caused by mutation in TTPA gene. The nerve conduction study (NCS) is an important step of evaluation and it shows neuropathy in about 90% of individuals. Vitamin E replacement may reverse some symptoms and possibly stop the disease progression but gait disturbances generally remain.

Method: Case-series study from tertiary neurology center. NCS and sequence analysis of TTPA were performed in all cases. The sample was evaluated with at least 06 months of vitamin E replacement. Both the Scale for the Assessment and Rating of Ataxia (SARA) and NCS were performed after 6 months of normal serum vitamin E levels.

Results: Ten consecutive patients were analyzed (5M / 5W). The median age was 21 years. The mean treatment duration was 5 years. Eighty percent of patients had normal serum vitamin E levels for at least 18 months. The SARA score were 16.6±8.3.
Thirty percent of the sample use unilateral support to walk and another 30% are restricted to wheelchair. NCS was normal in six patients, three showed mild purely sensory axonal polyneuropathy and one individual presented moderate motor sensory demyelinating polyneuropathy.  Biallelic variants were identified in all participants: p.Thr172Leufs*5 in 8 alleles (in homozygosis in 3 individuals), p.Glu249Asnfs*15 in 5 alleles (in homozygosis in one patient) and Ala120Thr (in homozygosis in one patient). Two variants have never been previously reported: p.Ala58Pro, present in homozygosis and p.Arg134Pro, which was in heterozygosis. It was not possible to determine a clear correlation between the genotype and the phenotype. There was no statistical significance of TTPA mutation or NCS with gait impairment in chronically vitamin E replacement patients.Time between symptom onset and treatment was the main factor associated with high SARA values.

Conclusion: Despite the small sample size, in our serie neither the NCS findings or TTPA mutation are associated with gait disturbances in AVED patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-ttpa-mutation-and-peripheral-nerve-involvement-in-gait-disturbances-in-ataxia-with-vitamin-e-deficiency-aved/