THE VALUE OF GENETICALLY DETERMINED DEFICIENCY OF ENZYMES IN THE FOLATE CYCLE IN THE PATHOGENESIS OF DISEASES OF THE AUTISTIC SPECTRUM
Keywords:
autistic spectrum, folic acid cycle, primary immunodeficiencyAbstract
Formulation of the problem. The results of a meta-analysis of randomized controlled clinical studies indicate an association of genetic folate cycle deficiency and autism spectrum disorders in children. Analysis of recent research and publications. There is some evidence that the immune system is involved in the pathogenesis of autism spectrum disorders, including an association with immunodeficiencies and histocompatibility loci, cases of autism after neuroinfections and autoimmune encephalitis, anomalously high microbial load, the effectiveness of immunotherapy. Formulating the purpose of the article. The goal is to study the genetic, biochemical and immunological changes in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Presenting main material. The results of the analysis of genetic tests indicate that the majority of children in the study group had 2-4 polymorphisms in the folate cycle enzyme genes (88% of cases), and the ratio of homo-and heterozygous forms can be represented as 1.2 to 1.0. An analysis of the biomarker results we obtained in the studied group showed the phenomenon of hyperhomocysteinemia in 88% of cases (p <0.05; Z <Z0.05), however, there was a significant fluctuation in the level of serum homocysteine concentration depending on a number of factors. The results of the study of the immune status showed that the genetic deficiency of the folate cycle through hyperhomocysteinemia leads to the development of a special form of primary immunodeficiency with variable immunological phenotype, but the predominant involvement of NK and NKT cells (р=0,01), CD8+ cytotoxic T-lymphocytes and myeloperoxidase of phagocytes (р=0,05), which will cause low resistance to intracellular microorganisms, tumors, and the propensity to develop systemic inflammation, autoimmune reactions, including anti-brain autoimmunity, and delayed type of hypersensitivity. Conclusions and perspectives of further research. Children with autism spectrum disorders associated with a genetic deficiency in the folate cycle are immunocompromised individuals. We propose a special form of primary immunodeficiency, noted in such cases, to define as “immunodeficiency associated with a genetic disorder of the folate cycle”. These data open up prospects for approbation of immunotherapy for autism spectrum disorders associated with a genetic deficiency of folic acid cycle enzymes.
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