Muhammad Mahajnah1, Dawn Corderio2, Valerie Austin2, Sarah Herd2, Carly Mutch3, Melissa Carter2, Eduard Struys4, Saadet Mercimek-Mahmutoglu5. 1. 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. 2. Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. 3. Occupational Therapy, Department of Rehabilitation Services, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Metabolic Laboratory, Department of Clinical Chemistry, VU Medical Centre, Amsterdam, The Netherlands. 5. 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.
Abstract
BACKGROUND: 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. PATIENT DESCRIPTION AND RESULTS: 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. CONCLUSIONS: 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. Crown
BACKGROUND: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. PATIENT DESCRIPTION AND RESULTS: 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. CONCLUSIONS: 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. Crown
Authors: Amal Al Teneiji; Theodora U J Bruun; Dawn Cordeiro; Jaina Patel; Michal Inbar-Feigenberg; Shelly Weiss; Eduard Struys; Saadet Mercimek-Mahmutoglu Journal: Metab Brain Dis Date: 2016-11-23 Impact factor: 3.584
Authors: Hilal H Al-Shekaili; Terri L Petkau; Izabella Pena; Tess C Lengyell; Nanda M Verhoeven-Duif; Jolita Ciapaite; Marjolein Bosma; Martijn van Faassen; Ido P Kema; Gabriella Horvath; Colin Ross; Elizabeth M Simpson; Jan M Friedman; Clara van Karnebeek; Blair R Leavitt Journal: Hum Mol Genet Date: 2020-11-25 Impact factor: 6.150