Coughlin Curtis R, Gospe Sidney M
Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Departments of Neurology and Pediatrics, University of Washington, Seattle, Washington, USA.
Ann Child Neurol Soc. 2023 Mar;1(1):24-37. doi: 10.1002/cns3.20016. Epub 2023 Mar 7.
Pyridoxine-dependent epilepsy (PDE) was historically defined by a dramatic clinical response to a trial of pyridoxine and the re-emergence of seizures after withdrawal of pyridoxine. Research conducted over the last seven decades has revealed that the phenotype of PDE results from multiple genetic disorders, and the most common disorder, PDE-, is caused by a deficiency of an enzyme involved in lysine metabolism. PDE- is characterized by more than epilepsy, as many patients have abnormalities of brain development, and most patients have intellectual and developmental disability. Treatment aimed at the underlying metabolic defect, in addition to pyridoxine supplementation, has improved clinical outcomes. Recently discovered biomarkers and genetic testing allow for the diagnosis of PDE- without the need of a pyridoxine trial and hold the promise for newborn screening. Despite these many advances, PDE- remains a clinical and biochemical conundrum. The increasing use of model systems and an international collaboration of clinician-scientists are among the reasons to be optimistic that these questions will be answered in the near future and that the clinical outcomes and quality of life will continue to improve for patients with PDE-.
吡哆醇依赖性癫痫（PDE）在历史上是通过对吡哆醇试验的显著临床反应以及停用吡哆醇后癫痫再次发作来定义的。过去七十年来的研究表明，PDE的表型源于多种遗传疾病，最常见的疾病PDE-是由赖氨酸代谢相关酶的缺乏引起的。PDE-的特征不止于癫痫，因为许多患者存在脑发育异常，且大多数患者有智力和发育障碍。除补充吡哆醇外，针对潜在代谢缺陷的治疗改善了临床结局。最近发现的生物标志物和基因检测使得无需进行吡哆醇试验就能诊断PDE-，并为新生儿筛查带来了希望。尽管取得了诸多进展，但PDE-仍然是一个临床和生化难题。模型系统的使用日益增加以及临床科学家的国际合作，让人们有理由乐观地认为，这些问题将在不久的将来得到解答，PDE-患者的临床结局和生活质量也将持续改善。
