Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine‐dependent epilepsy and pyridoxine phosphate oxidase deficiency

• Published in: Developmental medicine and child neurology Vol. 52; no. 7; pp. e133 - e142
• Main Authors: SCHMITT, BERNHARD, BAUMGARTNER, MATTHIAS, MILLS, PHILIPPA B, CLAYTON, PETER T, JAKOBS, CORNELIS, KELLER, ELMAR, WOHLRAB, GABRIELE
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2010
• Subjects: Aldehyde Dehydrogenase - genetics; Anticonvulsants - therapeutic use; Brain - physiopathology; Brain Diseases, Metabolic - diagnosis; Brain Diseases, Metabolic - drug therapy; Brain Diseases, Metabolic - physiopathology; Diagnosis, Differential; Electroencephalography; Epilepsy - diagnosis; Epilepsy - drug therapy; Epilepsy - physiopathology; Eye Movements; Female; Humans; Infant, Newborn; Mutation; Pyridoxal Phosphate - therapeutic use; Pyridoxaminephosphate Oxidase - deficiency; Pyridoxaminephosphate Oxidase - genetics; Pyridoxine - therapeutic use; Retrospective Studies; Seizures - diagnosis; Seizures - drug therapy; Seizures - physiopathology; Treatment Outcome
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/j.1469-8749.2010.03660.x

Aim  We report on seizures, paroxysmal events, and electroencephalogram (EEG) findings in four female infants with pyridoxine‐dependent epilepsy (PDE) and in one female with pyridoxine phosphate oxidase deficiency (PNPO). Method  Videos and EEGs were analysed and compared with videos of seizures and paroxysmal events archived from 140 neonates. PDE and PNPO were proven by complete control of seizures once pyridoxine or pyridoxal 5′‐phosphate was administered and by recurrence when withdrawn. Mutations in the antiquitin gene were found in three patients and in the PNPO gene in one child. Results  Seizures began within 48 hours after birth in four newborns and at age 3 weeks in one. Frequent multifocal and generalized myoclonic jerks, often intermixed with tonic symptoms, abnormal eye movement, grimacing, or irritability, were observed in all infants with PDE and PNPO, but rarely in the other archived videos of neonates. EEGs were inconstant and frequently no discernable ictal changes were recorded during the seizures and the paroxysmal events. In addition, interictal EEGs were inconclusive, with normal and abnormal recordings. In older children tonic–clonic seizures, abnormal behaviour, inconsolable crying, frightened facial expression, sleep disturbance, loss of consciousness, paraesthesia, or intermittent visual symptoms were described during controlled and uncontrolled withdrawal or insufficient dosage. Interpretation  PDE or PNPO should be considered in infants with prolonged episodes of mixed multifocal myoclonic tonic symptoms, notably when associated with grimacing and abnormal eye movements.