MTRR

At least 20 mutations in the MTRR gene have been identified in people with homocystinuria. Some of these mutations change single amino acids in methionine synthase reductase. Other mutations lead to an abnormally small, nonfunctional version of the enzyme. All these mutations prevent the enzyme from functioning normally. Without methionine synthase reductase, methionine synthase cannot convert homocysteine to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

A specific version (variant) of the MTRR gene may be associated with an increased risk of various health problems before birth. The variant (written as A66G) replaces a building block of DNA (nucleotide) called adenine with the nucleotide guanine at a specific location in the MTRR gene. This variant is associated with birth defects that occur during the development of the brain and spinal cord (neural tube defects). This variant may also increase the risk of having a child with Down syndrome, a condition characterized by intellectual disability and associated health problems. Researchers have not determined why there may be a connection between the A66G variant of the MTRR gene and the risk of neural tube defects or Down syndrome. Many factors play a part in determining the risk of these disorders.