Children With Stroke: Polymorphism of the MTHFR Gene, Mild Hyperhomocysteinemia, and Vitamin Status

Abstract

The aim of this study was to investigate a possible association among the thermolabile polymorphism, nucleotide 677 cytosine to thymidine point mutation (677 C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene, hyperhomocysteinemia, serum folate, vitamins B12 and B6, and stroke in children. Allele and genotype frequencies for the 677 C-->T polymorphism in 21 children with stroke and 28 healthy children of the same age were studied. No differences in allelic frequency were detected between the two populations. However, the prevalence of homozygous 677 C-->T was doubled in the stroke population (28.6%) compared to the healthy group (14.3%). Total plasma homocysteine (tHcy) levels were significantly increased in children aged 2 months to 15 years with stroke compared to reference values. No association was observed between the homozygous genotype (T/T) and hyperhomocysteinemia, nor between the T/T genotype and low folate levels (below the 95th percentile) in this group of patients. Vitamin concentrations in patients were not significantly different from reference values. Significant negative correlations were found between tHcy and folate and between tHcy and cobalamin, but not between tHcy and B6 concentrations. In summary, a higher prevalence of hyperhomocysteinemia and the 677 C-->T polymorphism were observed in children with stroke, but were not always associated. The systematic study of both abnormalities in children with stroke is recommended, so that hyperhomocysteinemia of any genetic origin can be corrected with vitamin supplementation. Moreover, the 677 C-->T genotype is a strong factor for predisposition to hyperhomocysteinemia and recurrent risk of stroke that might also be prevented with folate supplementation.

Cerebrovascular disorders in children

“…Chronic exchange transfusion or hydroxyurea should be considered in children with sickle cell-related AIS [53,54]. B-vitamin and folate supplementation has been recommended for children with the MTHFR mutation [55].…”

Antithrombotic Therapy in Neonates and Children

“…In Situ Thrombosis or Stroke of Undetermined Cause: In situ thrombosis may be idiopathic; secondary to local infl ammation; or secondary to prothrombotic conditions, including iron defi ciency anemia, [710][711][712] hyperhomocysteinemia, [712][713][714][715][716] elevated levels of lipoprotein(a), 218 and inherited prothrombotic disorders. 218,717,718 The overall risk of a recurrent AIS and TIA is 10% to 35%.…”

Thrombus obstructing the right ventricle outflow tract in a neonate with methylenetetrahydrofolate reductase 677TT genotype

“…Also, the role of homozygosity for the MTHFR 677TT mutation in the pathogenesis of stroke in the pediatric population is well known [2,12]. Thus, periventricular hyperechogenicity and dilatation of the lateral ventricles that are likely results of a hypoxic ischemic insult could be related to the maternal hyperhomocystinuria or fetal homozygous MTHFR 677TT.…”