A review of the biochemical pathways studied and abnormalities reported in the Rett syndrome

Burd, Larry; Kemp, Rob de; Knull, Harvey R.; Loveless, Douglas J.

doi:10.1016/s0387-7604(12)80081-7

Cited by 10 publications

(3 citation statements)

References 19 publications

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“…However, subsequent investigations showed that the urea cycle is normal in this disorder (Burd et al 1990). Analysis performed on blood, plasma and serum samples from RTT patients revealed either inconsistent abnormalities or no abnormalities (Riederer et al 1985;Plioplys et al 1994;Fiumara et al 1999).…”

Section: Abnormal Levels Of Biogenic Amine Metabolites In the Csf Of mentioning

confidence: 99%

Biogenic Amines in Rett Syndrome: The Usual Suspects

Roux

Villard

2009

Behav Genet

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Rett syndrome (RTT) is a severe postnatal neurological disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children, most biological parameters, including brain structure, are normal (although acquired microcephaly is usually present). However, in recent years, a deficit in bioaminergic metabolism has been identified at the cellular and molecular levels, in more than 200 patients. Recently available transgenic mouse strains with a defective Mecp2 gene also show abnormalities, strongly suggesting that there is a direct link between the function of the MECP2 protein and the metabolism of biogenic amines. Biogenic amines appear to have an important role in the pathophysiology of Rett syndrome, for several reasons. Firstly, biogenic amines modulate a large number of autonomic and cognitive functions. Secondly, many of these functions are affected in RTT patients. Thirdly, biogenic amines are the only neurotransmitters that have repeatedly been found to be altered in RTT patients. Importantly, pharmacological interventions can be envisaged to try to counteract the deficits observed. Here, we review the available human and mouse data and present how they have been and could be used in the development of pharmacological treatments for children affected by the syndrome. Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term.

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Section: Abnormal Levels Of Biogenic Amine Metabolites In the Csf Of mentioning

confidence: 99%

Biogenic Amines in Rett Syndrome: The Usual Suspects

Roux

Villard

2009

Behav Genet

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“…Some of these brain lipid changes are associated with neuropathological alterations, including loss of Purkinje cells, atrophy, synaptic and myelin abnormalities in frontal cortex [12][13][14][15]. Decreased serum levels of very long-chain fatty acids (VLCFA) and carnitine have also been evidenced in RTT patients [16,17]. It can be speculated that low carnitine levels impede transportation to mitochondria, thus inhibiting the oxidation of long-, medium-and short-chain fatty acids, which is to a certain extent compensated by intensified β-oxidation of VLCFA in the peroxisomal system [16].…”

Section: Lipid Metabolism In Rttmentioning

confidence: 99%

Fatty Acids and Autism Spectrum Disorders: The Rett Syndrome Conundrum

Felice¹,

Signorini²,

Leoncini³

et al. 2013

FNS

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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.

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“…Diagnosis of RS is based only on clinical features that have been very precisely de®ned by the Rett Syndrome Diagnostic Criteria Group. Despite this, the lack of a biochemical marker makes diagnosis very dicult or even doubtful and explains why various biochemical parameters are being examined [3,4]. Even if only secondary markers are found, they could play an important role in diagnosis, in elucidating pathogenesis and, ®nally, in therapy.…”

Section: Introductionmentioning

confidence: 99%