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J Nutr Biochem. 2019 Aug;70:38-46. doi: 10.1016/j.jnutbio.2019.04.004. Epub 2019 Apr 24.

The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children.

Author information

1
University of Tuscia, Department of Ecological and Biological Sciences, 01110 Viterbo, Italy.
2
University of Tuscia, Department of Science and Technology for Agriculture, Forestry, Nature and Energy, 01100 Viterbo, Italy.
3
University of Tuscia, Department of Science and Technology for Agriculture, Forestry, Nature and Energy, 01100 Viterbo, Italy. Electronic address: zolla@unitus.it.

Abstract

Autism spectrum disorder (ASD) is characterized by severe and persistent difficulties in social communication and social interaction at multiple levels. Recently, metabolic disorders have been associated with most cases of patients with ASD. The aim of this study was to investigate, through a new and more sophisticated mass technique, such as UHPLC-mass spectrometry (Q-exactive analyzer), alteration in metabolisms analyzing ASD children urine samples from children showing simultaneous vitamin B6, B9 and B12 deficiencies. This in order to study how these concurrent deficiencies may influence some phenotypic aspects of autistic disorder. Thus, urinary metabolic patterns specific to ASD were explored at an early age in 60 children with ASD, showing lower three vitamins levels, and 60 corresponding controls (age group 3-8, M: F=42:18). The results showed significant block of cystathionine formation with consequent accumulation of homocysteine. A lower glutathione levels (GSH), with reduction of essential intracellular reducing environment required for normal immune function, detoxification capacity and redox-sensitive enzyme activity. Increased concentration of 5-methyltetrahydrofolate, which leads to a lower availability of methyl group and significant decrease in urinary methionine and S-adenosyl-L-methionine (SAM) concentrations, the major methyl donor. The latter justify the well-known reduction in protein and DNA methylation reported in autistic children. As a final consideration, the concomitant deficiencies of all three B vitamins, recorded in a significant number of autistic children, suggests that intestinal dysbiosis in these patients may be the main cause of a reduction in their absorption, in addition to the genetic mutation of a specific gene.

KEYWORDS:

Autism; Metabolomics; Methylation; Vitamin B12; Vitamin B6; Vitamin B9

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