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Last updated: 04 January 2025 Print

Pyridoxal 5 Phosphate Dependent Epilepsy

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PNPO deficiencyPyridoxal 5 Phosphate Dependent EpilepsyPyridoxamine 5-Prime-Phosphate Oxidase DeficiencyPyridoxine-5'-phosphate oxidase deficiency

PNPO deficiency (OMIM 6032870) is an autosomal recessive inborn error of metabolism that leads to a seizure disorder, presenting in the newborn period (neonatal epileptic encephalopathy) or early infancy, that can be treated with pyridoxal 5’-phosphate but (classically) not pyridoxine. Seizures are often characterized by irregular involuntary muscle contractions (myoclonus), abnormal eye movements, and convulsions.

Mutations in the PNPO gene are responsible for pyridoxal 5'-phosphate-dependent epilepsy. The PNPO gene is responsible for the production of an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme plays a crucial role in metabolizing vitamin B6 from food, specifically pyridoxine and pyridoxamine, into its active form known as pyridoxal 5'-phosphate (PLP). PLP is crucial for various bodily processes, such as protein metabolism and the creation of neurotransmitters that facilitate brain signaling.

Classic PNPO deficiency 

  • defined as neonatal onset in premature infants and neonates

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