From the Department of Pediatrics (L.A.T., E.M.M.H.v.K., C.D.M.v.K.), Emma Children's Hospital, Amsterdam University Medical Center; On behalf of United for Metabolic Diseases (L.A.T., E.M.M.H.v.K., C.D.M.v.K.), The Netherlands; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center; Translational Metabolic Laboratory (K.L.M.C.), Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Section of Clinical Genetics and Metabolism (C.R.C.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; and Department of Pediatrics (C.D.M.v.K.), Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.
Neurology. 2022 Jun 14;98(24):1023-1028. doi: 10.1212/WNL.0000000000200711. Epub 2022 Apr 25.
We describe a neonate and a 14-month-old child presenting with seizures that were not (completely) controlled with antiepileptic medications. There were no signs of infection, and electrolytes and neuroimaging were normal. In the neonate, pyridoxine was administered followed by cessation of seizures, and a diagnosis of pyridoxine-dependent epilepsy (PDE-ALDH7A1, a neurometabolic disorder of lysine metabolism) was genetically confirmed. The 14-month-old child received a genetic diagnosis of PDE-ALDH7A1 after abnormalities in the metabolic investigations. Both children were treated with pyridoxine and adjunct lysine reduction therapy (LRT). Seizures were controlled completely, but both children are developmentally delayed. During her second pregnancy, the mother of the neonate was started on pyridoxine treatment because of the risk of PDE-ALDH7A1. After delivery, pyridoxine treatment was continued in the neonate, who did not show any clinical symptoms. Molecular analysis identified the familial variants consistent with the diagnosis of PDE-ALDH7A1. Adjunct LRT was initiated. This child has never experienced seizures, and development has been completely normal thus far (age 2.9 years), despite the shared genotype with their sibling with developmental delays (DDs). In conclusion, in neonates, infants, and children presenting with seizures of unknown origin with partial or no response to common antiepileptic medications, the diagnosis of PDE-ALDH7A1 or other pyridoxine-responsive genetic epilepsies should be considered, prompting a trial of pyridoxine as "diagnostic therapeuticum." The digital application (treatable-id.org) can support clinicians in the early diagnosis of treatable conditions in patients presenting with DD/intellectual disability of unknown cause.
我们描述了一名新生儿和一名 14 个月大的儿童，他们的癫痫发作无法（完全）用抗癫痫药物控制。他们没有感染迹象，电解质和神经影像学检查正常。在新生儿中，给予了吡哆醇，随后癫痫发作停止，基因诊断为吡哆醇依赖性癫痫（PDE-ALDH7A1，赖氨酸代谢的神经代谢障碍）。14 个月大的儿童在代谢研究异常后接受了 PDE-ALDH7A1 的基因诊断。两名儿童均接受了吡哆醇和辅助赖氨酸减少治疗（LRT）。癫痫完全得到控制，但两名儿童都有发育迟缓。在新生儿的第二次怀孕期间，由于 PDE-ALDH7A1 的风险，母亲开始接受吡哆醇治疗。分娩后，新生儿继续接受吡哆醇治疗，没有出现任何临床症状。分子分析确定了与 PDE-ALDH7A1 诊断一致的家族变异。辅助 LRT 开始。尽管与有发育迟缓（DD）的兄弟姐妹具有相同的基因型，但该儿童从未经历过癫痫发作，并且到目前为止发育完全正常（2.9 岁）。总之，对于出现不明原因癫痫发作且对常见抗癫痫药物部分或无反应的新生儿、婴儿和儿童，应考虑诊断为 PDE-ALDH7A1 或其他吡哆醇反应性遗传性癫痫，并试用吡哆醇作为“诊断治疗剂”。可应用数字应用程序（treatable-id.org）帮助临床医生早期诊断因未知原因出现 DD/智力残疾的患者的可治疗疾病。
