Kim Jiyoung, Pipitone Dempsey Angela, Kim Sun Young, Gunay-Aygun Meral, Vernon Hilary J
McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Case Rep Genet. 2022 Aug 30;2022:7138435. doi: 10.1155/2022/7138435. eCollection 2022.
Pyridoxine dependent-developmental and epileptic encephalopathy (PD-DEE) or pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in ALDH7A1. It classically presents as intractable infantile-onset seizures unresponsive to multiple antiepileptic drugs (AEDs) but with a profound response to large doses of pyridoxine (B6). We report a case of PDE with an atypical clinical presentation. The patient presented at 3 days of life with multifocal seizures, fever, increased work of breathing, decreased left ventricular systolic function, and lactic acidosis, raising suspicion for a mitochondrial disorder or infectious process. Within 1.5 weeks of presentation, seizure activity resolved with antiepileptic therapy. Whole exome sequencing (WES) revealed homozygous pathogenic variants in ALDH7A1 (c.1279G > , p.E427Q) and confirmed the diagnosis of PDE. Follow-up biochemical testing demonstrated elevated urine pipecolic acid. In the second week of life, the patient was initiated on triple therapy, including pyridoxine supplementation, low lysine diet, and arginine supplementation, which he tolerated well. Urine pipecolic acid levels responded accordingly after initiation of therapy. Our case illustrates the diagnostic challenges in PDE, the utility of rapid WES in such cases, and the response in urine pipecolic acid to therapy.
维生素B6依赖型发育性和癫痫性脑病（PD-DEE）或维生素B6依赖型癫痫（PDE）是一种罕见的常染色体隐性疾病，由ALDH7A1基因的双等位基因致病性变异引起。其典型表现为婴儿期起病的难治性癫痫发作，对多种抗癫痫药物（AEDs）无反应，但对大剂量维生素B6（B6）有显著反应。我们报告一例具有非典型临床表现的PDE病例。该患者出生3天时出现多灶性癫痫发作、发热、呼吸做功增加、左心室收缩功能下降和乳酸酸中毒，引发了对线粒体疾病或感染性疾病的怀疑。在就诊后1.5周内，癫痫活动通过抗癫痫治疗得到缓解。全外显子组测序（WES）显示ALDH7A1基因存在纯合致病性变异（c.1279G＞，p.E427Q），确诊为PDE。后续生化检测显示尿中哌可酸升高。在出生后第二周，患者开始接受三联疗法，包括补充维生素B6、低赖氨酸饮食和补充精氨酸，他耐受良好。治疗开始后尿中哌可酸水平相应下降。我们的病例说明了PDE的诊断挑战、快速WES在此类病例中的实用性以及尿中哌可酸对治疗的反应。
