Decreased MTHFR activity is more pronounced in the homozygous state than the heterozygous, and it does not appear to cause hyperhomocysteinemia in either genotype, but its combination with the C677T polymorphism—compound heterozygosity—results in significant elevation of plasma Hcy, even more severe than in 677TT individuals.8, 9, 10. The gene discussed is MTHFR; the disease is hyperhomocysteinemia.