Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency

Abstract

Ataxia with vitamin E deficiency is an autosomal recessive cerebellar ataxia caused by mutations in the a-tocopherol transfer protein coding gene localized on chromosome 8q, leading to lower levels of serum vitamin E. More than 91 patients diagnosed with ataxia with vitamin E deficiency have been reported worldwide. The majority of cases originated in the Mediterranean region, and the 744delA was the most common mutation among the 22 mutants previously described. We examined the clinical and molecular features of a large cohort of 132 Tunisian patients affected with ataxia with vitamin E deficiency. Of these patients, nerve conduction studies were performed on 45, and nerve biopsy was performed on 13. Serum vitamin E was dramatically reduced for 105 of the patients analysed. Molecular analysis revealed that 91.7% of the patients (n = 121) were homozygous for the 744delA mutation. Three other mutations were detected among the remaining patients (8.3%, n = 11) in the homozygous state. Two were previously reported (400C4T and 205-1G4T), and one was novel (553 + 1T4A). Age of onset was 13.2 AE 5.9 years, with extremes of 2 and 37 years. All described patients exhibited persistent progressive cerebellar ataxia with generally absent tendon reflexes. Deep sensory disturbances, pyramidal syndrome and skeletal deformities were frequent. Head tremor was present in 40% of the patients. Absence of neuropathy or mild peripheral neuropathy was noted in more than half of the cohort. This is the largest study of the genetic, clinical and peripheral neuropathic characteristics in patients with ataxia and vitamin E deficiency. The 744delA mutation represents the most common pathological mutation in Tunisia and worldwide, likely because of a Mediterranean founder effect. Our study led us to suggest that any patient displaying an autosomal recessive cerebellar ataxia phenotype with absent tendon reflexes and minor nerve abnormalities should first be screened for the 744delA mutation, even in the absence of a serum vitamin E measurement.

Protective effect of vitamin E against acute kidney injury

“…For example, considering the numerous important functions of vitamin E in the body, a vitamin E deficiency can result in many different diseases, including spinocerebellar ataxia [5], ataxia [6], myoclonus-dystonia syndrome [7], and various other diseases [8][9][10]. Furthermore, vitamin E has also been shown to be effective against certain diseases, such as cardiovascular diseases [11], Alzheimer's disease [12], and nephropathy [13].…”

Severe but reversible neuropathy and encephalopathy due to vitamin E deficiency

“…Most cases relate to a genetic defect by mutation of the TTPA gene, with homozygous 744delA mutation [1], in the presence of a predominant cerebellar syndrome.…”

“…Other rarer mutations of the TTPA gene are also described [1]. Vitamin E deficiency-related neuropathy due to pancreatic exocrine dysfunction is exceptional.…”

Ataxia in children: think about vitamin E deficiency ! (comment on: ataxia in children: early recognition and clinical evaluation)

“…[4]. The majority of the reported cases originated in the Mediterranean region, and the 744delA mutation (more specific in early onset form) was the most common among 22 known mutants [5]. …”