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Pyridoxal 5 Phosphate Dependent Epilepsy
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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
- 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
Discussion