Affiliations: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada | Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada
Note:  Corresponding author: Dr. Saadet Mercimek-Mahmutoglu, The Hospital for Sick Children, Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, 525 University Avenue, Suite 935, 9th Floor, Toronto, ON, M5G 1X8, Canada. Tel.: +1 416 813 7654/Ext. 201480; Fax: +1 416 813 5345; E-mail: [email protected]
Abstract: Pyridoxine dependent epilepsy (PDE) is an autosomal recessively inherited disorder. It is caused by mutations in the ALDH7A1 gene (PDE-ALDH7A1) encoding the alpha-aminoadipic semialdehyde dehydrogenase enzyme in the lysine catabolic pathway. The alpha-aminoadipic semialdehyde dehydrogenase enzyme deficiency leads to accumulation of alpha-aminoadipic semialdehyde and piperidine 6-carboxylic acid, the latter inactivates pyridoxal-5-phosphate. The majority of the patients present with neonatal onset intractable seizures with a dramatic response to pyridoxine therapy. Later seizure onset up to 3 yr of age has been reported too. Generalized tonic-clonic seizures are the most common seizure type. The treatment of PDE consists of high dose pyridoxine supplementation therapy. Since the underlying genetic defect was identified in the lysine catabolic pathway, few patients were treated with lysine-restricted diet to decrease, likely neurotoxic, alpha-aminoadipic semialdehyde and piperidine 6-carboxylic acid accumulation in the central nervous system.