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

Muhammad Mahajnah; Dawn Corderio; Valerie Austin; Sarah Herd; Carly Mutch; Melissa Carter; Eduard Struys; Saadet Mercimek-Mahmutoglu

doi:10.1016/j.pediatrneurol.2016.03.008

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

Pediatr Neurol. 2016 Jul:60:60-5. doi: 10.1016/j.pediatrneurol.2016.03.008. Epub 2016 Apr 13.

Authors

Muhammad Mahajnah¹, Dawn Corderio², Valerie Austin², Sarah Herd², Carly Mutch³, Melissa Carter², Eduard Struys⁴, Saadet Mercimek-Mahmutoglu⁵

Affiliations

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.

PMID: 27212567
DOI: 10.1016/j.pediatrneurol.2016.03.008

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.

Keywords: ALDHA71 gene; arginine supplementation; lysine-restricted diet; pyridoxine-dependent epilepsy.

Publication types

Case Reports

MeSH terms

Aldehyde Dehydrogenase / genetics*
Arginine / administration & dosage*
Child, Preschool
Dietary Supplements*
Epilepsy / diet therapy*
Epilepsy / genetics*
Humans
Lysine / deficiency*
Male
Mutation
Prospective Studies

Substances

Arginine
ALDH7A1 protein, human
Aldehyde Dehydrogenase
Lysine

Supplementary concepts

Pyridoxine-dependent epilepsy