A family with spinocerebellar ataxia type 8 expansion and vitamin E deficiency ataxia

Background: Ataxia with vitamin E deficiency is a recessive autosomal neurodegenerative disorder resembling the Friedreich ataxia phenotype but is due to mutations in the alpha-tocopherol transfer protein (TTPA) gene. In a recent article, we described a patient with ataxia carrying reduced serum vitamin E levels and showing CTA/CTG expansions of 320 triplet repeats in the SCA8 gene. Objectives: To perform a screening of the TTPA gene in the patient and to evaluate the effects of treatment with vitamin E on the patient's neurologic disturbances. Patient and Methods: We performed a single-strand conformation polymorphism and nucleotide sequence analysis of the 5 exons of the TTPA gene in the patient's family members. Results: The results indicated the patient to be a compound heterozygote for 2 mutations (in exon 3), each transmitted by one of the 2 parents, yielding a nonfunctional protein. Conclusions: We describe for the first time, to our knowledge, a mutated form of the TTPA gene in a patient also carrying an expansion in the SCA8 gene. The lack of improvement in the patient's symptoms on supplementation with alpha-tocopherol suggests that the SCA8 mutations may act in the neurodegeneration process, worsening the neurologic signs caused by the vitamin E deficit, and it could be speculated that the co-occurrence of mutant alleles for 2 distinct loci may influence the clinical course of the disease.