title: Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment.
abstract: 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.
authors.affiliation: Department of Neurology, The Royal Children's Hospital, Melbourne, Vic, Australia.
authors.forename: Tyson L
authors.initials: TL
authors.lastname: Ware
authors.forename: John
authors.initials: J
authors.lastname: Earl
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Peters
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Howell
authors.forename: James J
authors.initials: JJ
authors.lastname: Pitt
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Freeman
mesh_terms: D001928:Brain Diseases, Metabolic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*; D011733:Pyridoxamine / Q000097:blood* / Q000134:cerebrospinal fluid*; D011734:Pyridoxaminephosphate Oxidase / Q000172:deficiency* / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D014803:Vitamin B Complex; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D011734:Pyridoxaminephosphate Oxidase