MTHFR and hyperhomocysteinemia: The severe form of hyperhomocysteinemia (homocysteine >50 μmol/L) is rare, usually monogenic (autosomal recessive inheritance), and is caused by pathogenic variations in genes involved in homocysteine clearance, such as CβS, MTHFR and methylmalonic aciduria and homocystinuria type C (MMACHC).