This website provides information on patients with mutations in the PNPO gene, including clinical data, molecular data, management and research options.

Pyridoxamine-5'-phosphate oxidase (PNPO) deficiency is an autosomal recessive pyridoxal 5'-phosphate (PLP)-vitamin-responsive epileptic encephalopathy.The syndrome caused by mutations in the PNPO gene which encodes pyridoxine 5-prime-phosphate (PNP) oxidase, the rate-limiting enzyme in vitamin B6 synthesis, or pyridoxal 5-prime-phosphate (PLP). PNPO deficiency is a neurological disorder characterized by the occurrence of refractory seizures in the first year of life that is responsive to PLP or B6. Other systemic features including pre‐ and perinatal complications like pre‐maturity, fetal distress and intrauterine growth restriction (IUGR) with oligohydramnios. Metabolic acidosis and/or lactic acidosis were reported also in some cases.  Hematological manifestations in the form of normocytic anemia, normochromic anemia or pancytopenia, ophthalmological changes if form of pigmentary retinopathy and gastrointestinal tract (GIT) manifestations including abdominal distension, constipation and feeding intolerance often occur in PNPO deficiency.

First clinical report described by Bräutigam C, 2002, later the molecular identification Mills PB, 2005. Pyridoxal 5'-phosphate (PLP)-vitamin-responsive epilepsy is generally considered to be a rare cause of intractable neonatal seizures. As of 2019, 100 individuals with PNPO deficiency have been reported.

Not all individuals with the PNPO deficiency have the same features. Age of onset, type of seizure and PLP or B6 responsive are variable features between patients. Non-neurological manifestations are not seen in all cases.

Few more research questions might be valuable for clinical in the clinics regarding: Prenatal supplementation in PNPO deficiency has not been indicated yet, measuring PNPO enzyme activity through a rapid LC‐MS/MS‐based dried blood spot assay has also been proposed for rapid diagnosis of PNPO deficiency as well as newborn screening which is useful for the early detection of PNPO deficiency and might be feasible in PNPO deficiency.

This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the PNPO gene.

Malak Alghamdi, MD, Associate Professor, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Malghamdi@ksu.edu.sa
Nouran Adly, MD, King Saud University, Riyadh, Saudi Arabia, nouraadly@gmail.com