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Milestones in Friedreich ataxia: more than a century and still learning

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Abstract

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. FRDA is caused by expanded guanine-adenine-adenine (GAA) triplet repeats in the first intron of the frataxin gene (FXN), resulting in reduction of messenger RNA and protein levels of frataxin in different tissues. The molecular and metabolic disturbances, including iron accumulation, lead to pathological changes characterized by spinal cord and dorsal root ganglia atrophy, dentate nucleus atrophy without global cerebellar volume reduction, and hypertrophic cardiomyopathy. DNA analysis is the hallmark for the diagnosis of FRDA. There is no specific treatment to stop the disease progression in FRDA patients. However, a number of drugs are under investigation. Therapeutic approaches intend to improve mitochondrial functioning and to increase FXN expression.

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Acknowledgments

This work was supported by a grant from Fundação de Amparo à Pesquisa de São Paulo, FAPESP 2012/17494-3, São Paulo, Brazil.

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Authors and Affiliations

  1. Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Pedro de Toledo 650 Vila Clementino, São Paulo, 04039-002, SP, Brazil

    Agessandro Abrahão, José Luiz Pedroso & Orlando Graziani Povoas Barsottini

  2. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Agessandro Abrahão, José Luiz Pedroso, Patricia de Carvalho Aguiar & Orlando Graziani Povoas Barsottini

  3. Center of Health Sciences, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil

    Pedro Braga-Neto

  4. Division of Neurological Surgery, Sao Paulo University Medical School, São Paulo, Brazil

    Edson Bor-Seng-Shu

  5. Division of Movement Disorders, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil

    Patricia de Carvalho Aguiar

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  1. Agessandro Abrahão
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Abrahão, A., Pedroso, J.L., Braga-Neto, P. et al. Milestones in Friedreich ataxia: more than a century and still learning. Neurogenetics 16, 151–160 (2015). https://doi.org/10.1007/s10048-015-0439-z

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