Clinical and Genetic Study of Friedreich’s Ataxia and Ataxia with Vitamin E Deficiency in 44 Moroccan Families

Fatima Imounan,Ali Benomar,Ahmed Bouhouche,El Hachmia Aitbenhaddou,Wafa Regragui,Mohammed Yahyaoui,Naima Bouslam

doi:10.4236/wjns.2014.44033

Abstract

Introduction: Friedreich ataxia (FRDA) is a multi-system autosomal-recessive disease, the most common one of the genetically inherited ataxias. FRDA occurs as a consequence of mutations in the frataxin gene, with an expansion of a GAA trinucleotide. Ataxia with vitamin E deficiency (AVED) is characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich’s ataxia (FA) but serum concentrations of vitamin E are low. Aim of study: To study clinical and genetic features of the Friedreich’s ataxia and AVED patients in 44 Moroccan families. Patients and Methods: Retrospective series of 72 Moroccan patients displaying Friedreich’s ataxia syndrome was recruited over a period of 22 years (1987-2009). All patients had a clinical and ophtalmological examinations, 30 patients underwent electromyography, and CT scan was performed in 29 patients. GAA repeats in the frataxin gene and the 744 del A mutation α-TTP gene were performed in all patients. Results: 17 patients (24% of cases) had the 744 del A mutation in the α-TTP gene responsible of ataxia with vitamin E deficiency (AVED) phenotype. 55 patients (76% of cases) had GAA expanded allele in the first intron of the frataxin gene. Phenotype-genotype correlation revealed a high frequency of head titubation, decreased visual acuity and slower disease progression in AVED than in Friedreich’s ataxia phenotype (p Our study represents a large series which highlight the clinical and genetic differences between AVED and Friedreich’s ataxia. AVED patients have a better prognosis after alpha-tocopherol treatment.

Highlights

Friedreich ataxia (FRDA) is a multi-system autosomal-recessive disease, the most common one of the genetically inherited ataxias
We report clinical, genetic features and disease progression in 55 patients of GAA expansion and 17 patients with 744 Del A mutations in 44 Moroccan families
The MboII restriction site was absent in all the affected patients from the Ataxia with vitamin E deficiency (AVED) families, but it was found on the normal chromosomes of AVED family members

Summary

Introduction

Friedreich ataxia (FRDA) is a multi-system autosomal-recessive disease, the most common one of the genetically inherited ataxias. Ataxia with vitamin E deficiency (AVED) is characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich’s ataxia (FA) but serum concentrations of vitamin E are low. GAA repeats in the frataxin gene and the 744 del A mutation α-TTP gene were performed in all patients. Results: 17 patients (24% of cases) had the 744 del A mutation in the α-TTP gene responsible of ataxia with vitamin E deficiency (AVED) phenotype. Ataxia with isolated vitamin E deficiency (AVED) is a hereditary ataxia caused by mutations in the α-tocopherol transfer protein gene, α-TTP. Patients with AVED show clinical signs similar to those in Friedreich ataxia, including gait and limb ataxia, dysarthria, lower limb areflexia, loss of vibration and positional sense, and bilateral Babinski sign. The 744 Del A frame shift mutation is the most frequently found defect and is distributed as a result of a founder effect in North African and southern Italian patients [1]

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Conclusion