Pyridoxal 5 Phosphate Dependent Epilepsy

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.

• Intrauterine seizures, recognized by mothers as episodic, repetitive rhythmic movements
• Fetal distress before delivery
• Low APGAR scores
• Difficult-to-treat seizures irrespective of a history of fetal distress
• Epileptic encephalopathy or signs of encephalopathy (inconsolable crying, hyperalertness, jitteriness, irritability, dysregulation of muscle tone)
• Seizures and neurologic findings (e.g., roving eye movements, hypotonia, dystonia) and/or systemic signs (e.g., respiratory distress, anemia, failure to gain weight, abdominal distention, poor feeding)
• Cryptogenic infantile or epileptic spasms