The Effect of an Indigenous Drug on Abnormal Folate Metabolism and Intellectual Disability: A Study of 5,10-Methylenetetrahydrofolate Reductase Activity

Methylenetetrahydrofolate reductase, (MTHFR) is a key enzyme that is required to metabolize folate and is essential for normal development of central nervous system. Mutation in the MTHFR gene may result in elevated plasma homocysteine level. MTHFR C677T is most common polymorphism associated with impairment of cognitive function. In the present study, we examined the relationship between 677C>T MTHFR gene polymorphisms, homocysteine (tHcy) and the effect of test drug in the level of tHcy in the treated intellectual disability children (ID). Fifty patients of the both genders (male 31, female 19) with an age range of 8 to12 years with ID (cases) were selected from Pediatric O.P.D of S.S. Hospital I.M.S, B.H.U. ID children were clinically diagnosed according to the DSM V screening system. MTHFR C677T polymorphism was detected in the normal control vs.ID children by PCR-RFLP is using Hinf I enzyme. A total 30 out of 50 ID children were treated with the test formulation and remaining 20 ID children were placebo. Plasma homocysteine levels were measured by HPLC at initial, 3 & 6 months of study. CT of MTHFR C677T was higher in ID children than controls, although it did not show statistical significance (p=0.1) and the child T677T MTHFR genotype (TT) was found 4 % in ID children In the treated group, level of homocysteine dropped while increased in the placebo after six months of treatment. In treated group ID children, CC with genotype the level of tHcy dropped from 9.06 to 8.21; CT 11.92 to 10.15 whereas in placebo no such change was observed. Therefore, the present study showed MTHFR C677Tpolymorphism associated with modifying level of tHcy. The result indicated that ID children with the MTHFR C677T gene showing the highest level of tHcy, when treated with test formulation exerted reduction in tHcy concentration suggesting improved cognitive function due to homocysteine re-methylation. The present study also suggested an association of high degree of genetic heterogeneity because of their mutation in ID children. It is concluded that the test formulation has the potentiality to reduce the risk of MTHFR C677T gene mutation because of its activity and thus, improved the cognitive ability of ID children.