Early-onset vitamin B(6)-dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature.
Early-onset vitamin B(6)-dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature.
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DOI：
10.1002/jmd2.12183
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Donoghue S
中科院分区：
文献类型：
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作者：
Heath O;Pitt J;Mandelstam S;Kuschel C;Vasudevan A;Donoghue S
维生素B6依赖性癫痫是一组异质性疾病，其特征是活性辅因子吡哆醛-5 ′-磷酸（PLP）的可用性降低。虽然ALDH 7A 1或PNPO基因中的致病性变体导致了这些疾病的大多数病例，但PLPBP中的双等位基因致病性变体已被证明会导致一种形式的早发性维生素B6依赖性癫痫（EPVB 6D）。PLPBP被认为在维生素B6的稳态调节中发挥作用，通过向脱辅基酶提供PLP，同时限制与过量未结合PLP相关的副反应毒性。对吡哆醇和/或PLP有反应的新生儿顽固性癫痫发作是人类EPVB 6D的主要特征。与维生素B6依赖性癫痫的其他原因不同;然而，这种疾病的特定生物标志物尚未确定。在这里，我们提出的数据，从早产儿发现有致病性变异PLPBP，并提出早产可能提供一个额外的线索，早期考虑这种诊断。我们讨论了这些发现的背景下，以前发表的基因型，表型和代谢数据，从类似的患者。
Vitamin B6‐dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal‐5′‐phosphate (PLP). While pathogenic variants in ALDH7A1 or PNPO genes account for most cases of these disorders, biallelic pathogenic variants in PLPBP have been shown to cause a form of early onset vitamin B6‐dependent epilepsy (EPVB6D). PLPBP is thought to play a role in the homeostatic regulation of vitamin B6, 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 B6‐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 PLPBP 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.