Pyridoxamine 5′-phosphate oxidase deficiency


The PNPO gene provides instructions for producing an enzyme called pyridoxine 5′-phosphate oxidase. This enzyme is involved in the breakdown (metabolism) of vitamin B6. Specifically, it chemically modifies two forms of vitamin B6 derived from food (pyridoxine and pyridoxamine) to form pyridoxal 5′-phosphate (PLP). PLP is the active form of vitamin B6 and is necessary for many processes in the body, including protein metabolism and the production of chemicals that transmit signals in the brain (neurotransmitters). Pyridoxine 5′-phosphate oxidase is active (expressed) in cells throughout the body, with the highest amounts found in the liver.

At least 7 mutations in the PNPO gene have been found to cause pyridoxal 5′-phosphate-dependent epilepsy. Most of these mutations change one protein building block (amino acid) in the pyridoxine 5′-phosphate oxidase enzyme, impairing its normal function. The resulting enzyme cannot effectively metabolize pyridoxine and pyridoxamine to produce PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes that need PLP in order to be effective. It is not clear how the lack of PLP affects the brain and leads to the seizures that are characteristic of this condition.