A case for newborn screening for pyridoxine-dependent epilepsy

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
C. Coughlin, Laura A Tseng, C. V. van Karnebeek
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引用次数: 1

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.
新生儿吡哆醇依赖性癫痫筛查1例
由ALDH7A1突变引起的吡哆醇依赖性癫痫(PDH-ALDH7A1)是一种高度可治疗的发展性和癫痫性脑病。吡哆醇的药理学剂量与显著的临床癫痫发作改善有关,并且大多数患者单独使用吡哆醇即可达到充分的癫痫发作控制。不幸的是,一些PDE-ALDH7A1患者在做出诊断之前已经死亡,随后可以使用吡哆醇治疗,这突出了及时诊断的重要性。虽然对癫痫发作的控制至关重要,但单独使用吡哆醇治疗对正常结果是不够的,因为大多数患者会出现智力和发育迟缓。辅助赖氨酸还原治疗与显著的发育改善相关,尽管这些治疗如果在生命最初几个月后延迟,效果有限。最近确定了两种生物标志物,克服了以前新生儿筛查的技术障碍。在此,我们提供评论PDE-ALDH7A1符合当前和历史的新生儿筛查标准,并且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,也可以显着改善这种可治疗疾病中普遍存在的认知延迟。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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