ABSTRACT
A Ataxia de Friedreich é uma doença neurodegenerativa progressiva, de herança autossômica recessiva, que foi descrita pela primeira vez por Nicholaus Friedreich, em 1863. A mutação responsável por essa doença se encontra no cromossomo nove, onde ocorre uma expansão de trinucleotídios GAA. O gene afetado tem a função de codificar a proteína mitocondrial frataxina, que está envolvida no metabolismo do ferro. O principal sintoma é a ataxia (coordenação prejudicada), que, no início, é mais evidente nos membros inferiores e, posteriormente, atinge os membros superiores. Este estudo teve por objetivo relatar um caso de Ataxia de Friedreich, uma doença genética rara de caráter degenerativo que, ao contrário do prognóstico esperado, se manifestou mais tardiamente no indivíduo afetado. Este trabalho também descreve a evolução clínica, enfocando os sintomas e deficiências que o paciente apresentou antes e após o diagnóstico, bem como, discute as bases moleculares que podem ter contribuído para a manifestação tardia da doença, além dos tratamentos emergentes.
The Friedreich?s ataxia is a progressive neurodegenerative disease with autosomal recessive inheritance, which was first described by Nicholaus Friedreich in 1863. The mutation responsible for this disease is located on chromosome nine, where there is a GAA trinucleotide expansion repeats. The affected gene function is to encode the mitochondrial protein frataxin, which is involved in the iron metabolism. The main symptom is ataxia (impaired coordination), which at first is more evident in the lower limbs and eventually reaches the upper limbs. This study aimed to report a case of Friedreich?s Ataxia, a rare genetic disease with degenerative characteristic that manifested itself later in the affected individual unlike the expected outcome. This paper also describes the clinical course, focusing on the symptoms and disabilities that the patient presented before and after diagnosis, and also discusses the molecular basis that may have contributed to the late-onset of the disease besides the emerging treatments.
Subject(s)
Humans , Animals , Male , Friedreich Ataxia/classification , Friedreich Ataxia/complications , Iron/metabolism , Gait AtaxiaABSTRACT
The present review traces the origin of Friedreich's Ataxia (FA) from the time of Nikolaus Friedreich in the mid-nineteenth century. The early hesitation on the part of the neurological community in accepting FA as a distinct entity, rather than a variant form of tabes dorsalis and multiple sclerosis, has been highlighted. Research within the last 6-7 years, has firmly established FA as a trinucleotide repeat disorder, the location of the offending gene, and the disease-related gene product, frataxin. Frataxin is now thought to interfere with the mitochondrial oxidative process and enhance iron accumulation. However, whether this iron accumulation is a primary causative event for symptom production is not clear and iron chelators are unlikely to be helpful in therapy. Of great promise is the use of free radical scavengers and antioxidants. One such agent idebenone, a short chain analogue of co-enzyme Q10, may have a future.