title: A Prospective Case Study of the Safety and Efficacy of Lysine-Restricted Diet and Arginine Supplementation Therapy in a Patient With Pyridoxine-Dependent Epilepsy Caused by Mutations in ALDH7A1.
abstract: Pyridoxine-dependent epilepsy (PDE) is caused by mutations in ALDH7A1 (PDE-ALDH7A1), which encodes α-aminoadipic semialdehyde dehydrogenase in the lysine catabolic pathway, resulting in accumulation of α-aminoadipic-acid-semialdehyde.
  
  
  
  We present a three-year treatment outcome of a child with PDE-ALDH7A1 on pyridoxine (started at age three weeks of age), lysine-restricted diet (started at age seven months), and arginine supplementation therapy (started at age 26 months). He had a markedly elevated urinary α-aminoadipic-acid-semialdehyde (39.6 mmol/mol of creatinine; reference range = 0 to 2) and compound heterozygous mutations in ALDH7A1 (c.446C>A and c.919C>T). He has been seizure free since the age three weeks. He achieved normal cognitive function at age 3.5 years. He exhibited gross motor delay after the age 13 months. Tryptophan supplementation was added for the mild cerebral serotonin deficiency at the thirteenth month of therapy. Arginine supplementation was added to achieve further decrease in the cerebrospinal fluid α-aminoadipic-acid-semialdehyde levels at the 26th month of therapy. His cerebrospinal fluid α-aminoadipic-acid-semialdehyde levels were markedly decreased on this combined therapy.
  
  
  
  This treatment was well tolerated. Mild cerebral serotonin deficiency was the only biochemical effect with no clinical features. Despite excellent compliance and strict treatment regimen, cerebrospinal fluid α-aminoadipic-acid-semialdehyde levels did not normalize.
authors.affiliation: Child Neurology and Development Center, Department of Pediatrics, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mahajnah
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Dawn
authors.initials: D
authors.lastname: Corderio
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Austin
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Herd
authors.affiliation: Occupational Therapy, Department of Rehabilitation Services, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Carly
authors.initials: C
authors.lastname: Mutch
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Carter
authors.affiliation: Metabolic Laboratory, Department of Clinical Chemistry, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: Eduard
authors.initials: E
authors.lastname: Struys
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: saadet.mahmutoglu@sickkids.ca.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D001120:Arginine / Q000008:administration & dosage*; D002675:Child, Preschool; D019587:Dietary Supplements; D004827:Epilepsy / Q000178:diet therapy* / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000172:deficiency*; D008297:Male; D009154:Mutation; D011446:Prospective Studies
chemical_list: D001120:Arginine; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D008239:Lysine
keywords: ALDHA71 gene; arginine supplementation; lysine-restricted diet; pyridoxine-dependent epilepsy