Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is an autosomal recessive disorder and the most common inborn error of folate metabolism. The MTHFR C677T polymorphism results from a missense mutation at nucleotide 677 (C→T) in the MTHFR gene. This substitution replaces alanine (Ala) with valine (Val) at position 677, creating an HinfI restriction site.
Homozygosity or heterozygosity for this mutation reduces MTHFR enzymatic activity, decreasing the synthesis of 5-methyltetrahydrofolate, the primary methyl donor in the conversion of homocysteine to methionine. This can lead to hyperhomocysteinemia, homocystinuria, and hypomethioninemia, which are risk factors for venous and arterial thrombosis, cardiovascular disease, and neurologic complications.
MTHFR polymorphism has also been associated with recurrent spontaneous abortion and may contribute to pregnancy complications such as preeclampsia. The mutation is more prevalent in women with severe preeclampsia and increases thrombosis risk when combined with Factor V Leiden mutation. Detection is performed using molecular analysis.
Polymerase Chain Reaction (PCR) with reverse hybridization.
Reported as: