Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an examination of C677T and A1298C mutations.

Although rare in children, stroke is becoming increasingly recognized as an important cause of morbidity and mortality with an annual incidence of approximately 3 per 100,000 per year. While several studies have documented the underlying mechanisms and pathogenesis related to stroke in adults, including genetic and acquired prothrombotic conditions, the data available on similar conditions in children is limited. Evidence suggests that mutations in methylenetetrahydrofolate reductase (MTHFR) appear to be linked with hyperhomocysteinemia (HHC) and cerebral-thrombotic events in children. While the C677T common missense mutation is the best-characterized MTHFR polymorphism, another common missense mutation, A1298C also exists. A recent study of children demonstrated that the homozygous form of C677T polymorphism occurred two-times as often in those with stroke versus healthy controls. In our retrospective chart review of 33 children seen at Children's Hospital of Orange County from January 1, 2000 to September 30, 2003 with the diagnosis of stroke, we examined both the C677T and A1298C polymorphisms for occurrence and type. In the subset (n=21), which excluded those with a confounding disorder, we observed a significant increase in the frequency of A1298C and C677T homozygosity (0.25 [p=0.01] and 0.20 [p=0.100], respectively); expected rate: (0.06 and 0.08, respectively). Our observed rates of heterozygosity for both MTHFR mutations (0.35 and 0.40, respectively) were consistent with expected rates (0.28 and 0.38, respectively). In all subjects, homocysteine (HC) levels were normal. The results of our study suggest that mutations in MTHFR are associated with pediatric stroke. However, additional studies are required to confirm our findings and to determine if this relationship is causal.