Hassel Bjørnar, Rogne Ane Gretesdatter, Hope Sigrun
Department for Neurohabilitation, Oslo University Hospital and University of Oslo, Oslo, Norway.
Norwegian Defence Research Establishment (FFI), Kjeller, Norway.
Front Psychiatry. 2019 Mar 8;10:116. doi: 10.3389/fpsyt.2019.00116. eCollection 2019.
Pyridoxine (vitamin B6)-responsive epilepsies are severe forms of epilepsy that manifest as seizures immediately after birth, sometimes , sometimes months, or years after birth. Seizures may be treated efficiently by life-long supplementation with pyridoxine or its biologically active form, pyridoxal phosphate, but even so patients may become intellectually disabled, for which there currently is no effective treatment. The condition may be caused by mutations in several genes (, or ). Mutations in , and entail build-up of reactive aldehydes (α-aminoadipic semialdehyde, γ-glutamic semialdehyde) that may react non-enzymatically with macromolecules of brain cells. Such reactions may alter the function of macromolecules, and they may produce "advanced glycation end products" (AGEs). AGEs trigger inflammation in the brain. This understanding points to aldehyde-quenching, anti-AGE, or anti-inflammatory therapies as possible strategies to protect cognitive development and prevent intellectual disability in affected children. Studies on how aldehydes traverse cell membranes and how they affect brain function could further the development of therapies for patients with pyridoxine-responsive epilepsies.
维生素B6反应性癫痫是严重的癫痫形式，在出生后立即、有时在出生后数月或数年出现癫痫发作。癫痫发作可通过终身补充维生素B6或其生物活性形式磷酸吡哆醛进行有效治疗，但即便如此，患者仍可能出现智力残疾，目前对此尚无有效治疗方法。这种疾病可能由多个基因（ 、 或 ）的突变引起。 、 和 的突变会导致反应性醛类物质（α-氨基己二酸半醛、γ-谷氨酸半醛）的积累，这些醛类物质可能会与脑细胞的大分子发生非酶反应。此类反应可能会改变大分子的功能，并可能产生“晚期糖基化终末产物”（AGEs）。AGEs会引发脑部炎症。这一认识表明，醛淬灭、抗AGE或抗炎疗法可能是保护受影响儿童认知发育和预防智力残疾的策略。关于醛类物质如何穿过细胞膜以及它们如何影响脑功能的研究，可能会推动维生素B6反应性癫痫患者治疗方法的发展。
