Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA.
Department of Pediatrics, Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Cold Spring Harb Mol Case Stud. 2022 Mar 24;8(2). doi: 10.1101/mcs.a006197. Print 2022 Feb.
Pyridoxine-dependent epilepsy due to mutations in (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.
由于 （PDH-ALDH7A1）突变导致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。大剂量的吡哆醇与显著的临床癫痫改善相关，大多数患者仅用吡哆醇即可获得足够的癫痫控制。不幸的是，一些 PDE-ALDH7A1 患者在做出诊断并随后进行吡哆醇治疗之前已经死亡，这突出了及时诊断的重要性。尽管吡哆醇治疗对于控制癫痫发作至关重要，但单独使用吡哆醇不足以获得正常的结果，因为大多数患者都存在智力和发育迟缓。赖氨酸还原治疗辅助治疗与显著的发育改善相关，尽管这些治疗在生命的头几个月后延迟使用时效果有限。最近，两种生物标志物被确定，克服了新生儿筛查以前的技术障碍。在此，我们评论说，PDE-ALDH7A1 符合当前和历史上的新生儿筛查标准，并且新生儿诊断和治疗可以降低不受控制的癫痫发作导致的死亡率，并显著改善这种可治疗疾病中普遍存在的认知延迟。
