Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment

Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal‐5′‐phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video‐electroencephalographic (EEG) findings described. The first child showed electro‐clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well‐controlled epilepsy with pyridoxal‐5′‐phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal‐5′‐phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure‐free with pyridoxal‐5′‐phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal‐5′‐phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal‐5′‐phosphate treatment cannot be relied upon to diagnose PNPO deficiency.