Heath Oliver, Pitt James, Mandelstam Simone, Kuschel Carl, Vasudevan Anand, Donoghue Sarah
Department of Metabolic Medicine The Royal Children's Hospital Melbourne Australia.
Department of Biochemical Genetics, Victorian Clinical Genetics Service Murdoch Children's Research Institute Melbourne Australia.
JIMD Rep. 2020 Nov 15;58(1):3-11. doi: 10.1002/jmd2.12183. eCollection 2021 Mar.
Vitamin B-dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal-5'-phosphate (PLP). While pathogenic variants in or genes account for most cases of these disorders, biallelic pathogenic variants in have been shown to cause a form of early onset vitamin B-dependent epilepsy (EPVB6D). PLPBP is thought to play a role in the homeostatic regulation of vitamin B, by supplying PLP to apoenzymes while limiting side-reaction toxicity related to excess unbound PLP. Neonatal-onset intractable seizures that respond to pyridoxine and/or PLP are a predominant feature of EPVB6D in humans. Unlike other causes of vitamin B-dependent epilepsies; however, a specific biomarker for this disorder has yet to be identified. Here we present data from a premature infant found to have pathogenic variants in and propose that prematurity may provide an additional clue for early consideration of this diagnosis. We discuss these findings in context of previously published genotypic, phenotypic, and metabolic data from similarly affected patients.
维生素B依赖型癫痫是一组异质性疾病，其特征是活性辅因子磷酸吡哆醛（PLP）的可用性降低。虽然 或 基因中的致病变异占这些疾病的大多数病例，但已证明 基因的双等位基因致病变异会导致一种早发性维生素B依赖型癫痫（EPVB6D）。PLPBP被认为通过向脱辅基酶供应PLP，同时限制与过量未结合PLP相关的副反应毒性，在维生素B的稳态调节中发挥作用。对吡哆醇和/或PLP有反应的新生儿期难治性癫痫是人类EPVB6D的主要特征。然而，与维生素B依赖型癫痫的其他病因不同，这种疾病的特定生物标志物尚未确定。在这里，我们展示了一名早产儿的数据，该早产儿被发现有 基因的致病变异，并提出早产可能为早期考虑这一诊断提供额外线索。我们结合先前发表的来自类似受影响患者的基因型、表型和代谢数据来讨论这些发现。
