Fatty Acids and Autism Spectrum Disorders: The Rett Syndrome Conundrum

Claudio De Felice, Cinzia Signorini, Silvia Leoncini, Alessandra Pecorelli, Thierry Durand, Jean-Marie Galano, Valérie Bultel-Poncé, Alexandre Guy, Camille Oger, Gloria Zollo, Giuseppe Valacchi, Lucia Ciccoli, Joussef Hayek

Child Neuropsychiatry Unit, University Hospital AOUS, Policlinico “S. M. Alle Scotte”, Siena, Italy.
Department of Life Science and Biotechnologies, University of Ferrara, Ferrara, Italy;Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea..
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy;Child Neuropsychiatry Unit, University Hospital AOUS, Policlinico “S. M. Alle Scotte”, Siena, Italy.
Institut des Biomolécules Max Mousseron (IBMM), Montpellier, France.
Neonatal Intensive Care Unit, University Hospital AOUS, Policlinico “S. M. Alle Scotte”, Siena, Italy.

DOI: 10.4236/fns.2013.49A1012                

Abstract

Autism spectrum disorders (ASDs) are epidemically explosive clinical entities, but their pathogenesis is still unclear and a definitive cure does not yet exist. Rett syndrome (RTT) is a rare genetically determined cause of autism linked to mutations in the X-linked MeCP2 gene or, more rarely, in CDKL5 or FOXG1. A wide phenotypical heterogeneity is a known feature of the disease. Although several studies have focused on the molecular genetics and possible protein changes at different levels, to date very little attention has been paid to fatty acids in this disease, which could be considered as a natural paradigm for the ASDs. To this regard, a quite enigmatic feature of the disease is the evidence in the affected patients of an extensive peroxidation of polyunsaturated fatty acids (arachidonic acid, AA, docosaexahenoic acid, DHA, adrenic acid, AdA and, to a lesser extent, eicosapentaenoic acid, EPA), in contrast with amelioration of the redox changes and phenotypical severity following the supplementation of some of those same fatty acids (DHA + EPA). Therefore, fatty acids may represent a kind of Janus Bifrons in the particular context of RTT. Here, we propose a rational explanation for this apparent “fatty acid paradox” in RTT. A better understanding of this paradox could also be of help to get a better insight into the complex mechanism of action for polyunsaturated fatty acids in health and disease.

Keywords

Fatty Acids; Arachidonic Acid; Docosahexaenoic Acid; Adrenic Acid; Eicosapentaenoic Acid; Rett Syndrome; Autism Spectrum Disorders

Conflicts of Interest

The authors declare no conflicts of interest.

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