Biochemical profile of children with autism spectrum disorders associated with genetic deficiency of the folate cycle

Abstract

Introduction: the results of 5 randomized controlled meta-analysis studies showed the association between genetic deficiency of folate cycle and autistic spectrum disorders in children. The purpose of the present study is to investigate the biochemical alterations in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Methods: the experimental group involved 225 children diagnosed with autism spectrum disorders (Diagnostic and Statistical Manual of Mental Disorders IV-TR, International Statistical Classification of Diseases and Related Health Problems 10), who suffered from a genetic deficiency of the folate cycle (methylenetetrahydrofolate reductase C677T + methylenetetrahydrofolate reductase A1298C and/or methionine synthase A2756G and/or methionine synthase reductase A66G; polymerase chain reaction). The control group included 51 healthy children who followed the same age and gender distribution pattern of the patients group. Results: the study revealed that the patients had a specific pattern of biochemical alterations in serum (p<0.05; Z <5.2); deficiencies of vitamins: B6 [6.32 (3.58) μg/L, r.i. 8.7-27.2], folic acid [2.97 (6.85) pg/mL, r.i. 3.89-26.8], B12 [112.64 (374.2) pg/mL, r.i. 197-771], and D3 [13.98 (20.41) ng/mL, r.i. 30-60]; hypercreatininemia [69.13 (64.21) μmol/L, r.i. 3 years: 21-36, 3-5 years: 27-42, 5-8 years: 28-50], increased creatine kinase [314.12 (443.42) U/L, r.i. 39-308 U/L]; and lactate dehydrohenase [378.47 (443.72) U/L, r.i.135-225]. At the time of examination, an increase in the serum concentration of homocysteine was registered in 88% of the patients. The associations between different folate cycle genes polymorphisms with certain biochemical abnormalities were shown Discussion: autism spectrum disorders associated with genetic deficiency of the folate cycle in children are characterized by a specific pattern of biochemical changes that is not found in healthy children and may be involved in the pathogenesis of immunodeficiency and encephalopathy. These data can be used in clinical practice for diagnostic purposes to identify a subgroup of children with autism spectrum disorders associated with genetic folate cycle deficiency and for the selection of biochemical correction during treatment.