Common mutations at the homocysteine metabolism pathway and pediatric stroke

Heterozygosity and/or homozygosity for mutations at the genes of the enzyme s involved in homocysteine metabolism may confer an increased risk for thro mbosis by causing hyperhomocysteinemia. Although the mutations related to h omocysteine metabolism possibly increase the risk of stroke, the data are c onflicting and there are very few reports linking these defects to acute st roke in children. We aimed to study the role of these mutations in Turkish children with ischemic stroke. Forty-six patients having cerebral infarct w ere clinically diagnosed, and the infarction verified with magnetic resonan ce imaging of the brain was included in the study. All patients were below the age of 18 (10 months to 18 years). Sixty-eight controls, consecutively selected among healthy unrelated subjects from the same geographic area of Turkey without personal and family history of thrombosis, stroke or Behest' s disease, were included. Genotyping for the common mutations was carried o ut by the methods described previously. There was no difference between the pediatric stroke patients and controls for the distribution of methylene t etrahydrofolate reductase (MTHFR) 677 C-T, MTHFR 1298 A-C, methylene tetrah ydrofolate dehydrogenase (MTHFD) 1958 G-A and methionine synthase reductase (MTRR) 66 A-G alleles. There was no risk for double alterations (MTHFR 677 C-T vs. 1298 A-C) after individuals with FV 1691 A mutation is excluded. T welve of the 46 patients were found to carry FV 1691 A mutation (26.0%), on e being homozygote. The cerebral infarct risk for FV 1691 A was found to be 6.4 (CI 95% 1.7-23.0). Eight of the 46 patients were found to carry PT 202 10 A mutation (16.6%). Two of the FV 1691 A heterozygous patients carried P T 20210 A mutation at the same time (4.2%). As a conclusion, we can say tha t FV 1691 A and PT 20210 A mutations are important and must be included to the routine analysis of pediatric stroke patients. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.