Accumulation of fumarate to millimolar levels due to inactivating mutations of fumarate hydratase (FH) is found in the genetic disorder fumaric aciduria, as well as the hereditary leiomyomatosis and renal cell cancer (HLRCC)73, in which fumarate causes hypermethylation of DNA by inhibiting TET enzymes to trigger epithelial-mesenchymal transition (EMT)74. Here, FH is linked to hereditary disease.