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 patients achieve adequate seizure control with pyridoxine alone. Unfortunately, some patients with PDE-ALDH7A1 have died prior to when the diagnosis was made and subsequent treatment with pyridoxine could be implemented, 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.
摘要：
由于ALDH7A1（PDH-ALDH7A1）突变引起的吡哆醇依赖性癫痫是一种高度可治疗的发育性和癫痫性脑病。吡哆醇的药物剂量与临床癫痫发作的显着改善有关，大多数患者仅使用吡哆醇即可达到足够的癫痫发作控制。不幸的是,一些PDE-ALDH7A1患者在做出诊断之前已经死亡，随后可以实施吡哆醇治疗，强调及时诊断的重要性。尽管对控制癫痫发作至关重要，吡哆醇单独治疗对于正常结果是不够的，因为大多数患者患有智力和发育迟缓。辅助赖氨酸减少疗法与显着的发育改善有关，尽管如果在生命的最初几个月后延迟，这些治疗的疗效有限。最近，确定了两种生物标志物，它们克服了先前用于新生儿筛查的技术障碍。在这里，我们提供PDE-ALDH7A1符合新生儿筛查的当前和历史标准的评论，新生儿诊断和治疗既可以降低不受控制的癫痫发作的死亡率，又可以显着改善这种可治疗疾病中普遍存在的认知延迟。
