MTHFR is the rate-limiting enzyme in the methyl cycle, which includes the conversion of homocysteine into methionine. Defects in variants of MTHFR can therefore lead to hyperhomocysteinemia. There are two common variants of MTHFR deficiency. In the more significant of the two, the individual is homozygous for the 677T polymorphism. This variant in particular is the most common genetic cause of hyperhomocysteinemia. The resulting enzyme is thermolabile and in homozygotes, enzymatic activity is depressed to 35% of its usual level. The second variant is a milder one, caused by a homologous 1298C polymorphism. This leads to 68% of the control values of enzyme activity, and it normally does not lead to low serum folate.
Methylenetetrahydrofolate reductase deficiency
Dihydrofolate reductase deficiency
Adenine phosphoribosyltransferase deficiency
Guanidinoacetate methyltransferase deficiency
5,10-methenyltetrahydrofolate synthetase deficiency
Purine nucleoside phosphorylase deficiency
Dihydropyrimidine dehydrogenase deficiency
Adenosine deaminase 2 deficiency