A case for newborn screening for pyridoxine-dependent epilepsy
Open Access
- 25 February 2022
- journal article
- editorial
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Molecular Case Studies
- Vol. 8 (2)
- https://doi.org/10.1101/mcs.a006197
Abstract
Pyridoxine dependent epilepsy due to mutations in ALDH7A1 (PDH-ALDH7A1) is a highly treatable developmental and epileptic encephalopathy. Pharmacologic doses of pyridoxine are associated with dramatic clinical seizure improvement and most patient achieve adequate seizure control with pyridoxine alone. Unfortunately, patients with PDE-ALDH7A1 have died prior to diagnosis and subsequent treatment with pyridoxine highlighting the importance of a timely diagnosis. Although critical for seizure control, pyridoxine treatment alone is not sufficient for normal outcomes as most patients suffer intellectual and developmental delay. Adjunct lysine reduction therapies are associated with significant developmental improvements although these treatments have limited efficacy if delayed after the first few months of life. Recently two biomarkers were identified that overcome previous technical hurdles for newborn screening. Herein we provide commentary that PDE-ALDH7A1 meets both current and historic criteria for newborn screening, and that a neonatal diagnosis and treatment can both reduce mortality from uncontrolled seizures and significantly improve the cognitive delay that is pervasive in this treatable disorder.Keywords
This publication has 74 references indexed in Scilit:
- Normal plasma pipecolic acid level in pyridoxine dependent epilepsy due to ALDH7A1 mutationsMolecular Genetics and Metabolism, 2013
- Pyridoxine-dependent Epilepsy With Elevated Urinary α-Amino Adipic Semialdehyde in Molybdenum Cofactor DeficiencyPEDIATRICS, 2012
- The measurement of urinary Δ1‐piperideine‐6‐carboxylate, the alter ego of α‐aminoadipic semialdehyde, in Antiquitin deficiencyJournal of Inherited Metabolic Disease, 2012
- Revisiting the Wilson-Jungner criteria: how can supplemental criteria guide public health in the era of genetic screening?Genetics in Medicine, 2012
- Long-term follow-up in two siblings with pyridoxine-dependent seizures associated with a novel ALDH7A1 mutationEuropean Journal of Paediatric Neurology, 2011
- Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)Brain, 2010
- Antenatal treatment in two Dutch families with pyridoxine-dependent seizuresEuropean Journal of Pediatrics, 2009
- α-Aminoadipic semialdehyde is the biomarker for pyridoxine dependent epilepsy caused by α-aminoadipic semialdehyde dehydrogenase deficiencyMolecular Genetics and Metabolism, 2007
- Pyridoxine‐dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regimeDevelopmental Medicine and Child Neurology, 2007
- MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiencyThe Journal of Pediatrics, 2003