Plecko Barbara, Stöckler Sylvia
Division of Biochemical Diseases and Cystic Fibrosis, Children's and Women's Health Center, University of British Columbia, Vancouver, BC, Canada.
Can J Neurol Sci. 2009 Aug;36 Suppl 2:S73-7.
Vitamin B6 is an abundant cofactor in aminoacid- and neurotransmitter metabolism. Physiologic availability depends on dietary supply, intact absorption and conversion of pyridoxamine and pyridoxine into the only active cofactor, pyridoxal-5'-phosphate (PLP) in liver. By now we know of four genetic epilepsies with vitamin B6 dependent seizures. Two are caused by reduced synthesis/availability of PLP (Pyridox(am)in-phosphate oxidase (PNPO) deficiency and infantile hypophosphatasia) and two by increased utilization/inactivation (pyridoxine-dependent epilepsy and hyperprolinemia type II). Aside from hyperprolinemia type II these disorders usually present with therapyresistant (myoclonic) seizures in the neonatal period. The EEG findings may range from burst suppression pattern to unspecific slowing or may even be normal. All four disorders can be diagnosed by reliable biomarkers and be confirmed by molecular analysis of the respective genes. While PLP would benefit all four entities, PNPO patients are typically resistant to pyridoxine and need PLP substitution. Especially in neonatal, therapyresistant seizures, these disorders have to be considered early, to prevent irreversible neurologic damage.
维生素B6是氨基酸和神经递质代谢中一种丰富的辅助因子。其生理可用性取决于饮食供应、完整的吸收以及吡哆胺和吡哆醇在肝脏中转化为唯一的活性辅助因子——磷酸吡哆醛（PLP）。目前我们已知有四种维生素B6依赖性癫痫。其中两种是由于PLP的合成/可用性降低（磷酸吡哆（胺）氧化酶（PNPO）缺乏症和婴儿低磷酸酯酶症），另外两种是由于利用率/失活增加（吡哆醇依赖性癫痫和II型高脯氨酸血症）。除了II型高脯氨酸血症外，这些疾病通常在新生儿期表现为治疗抵抗性（肌阵挛性）癫痫发作。脑电图结果可能从爆发抑制模式到非特异性减慢，甚至可能正常。所有这四种疾病都可以通过可靠的生物标志物进行诊断，并通过对各自基因的分子分析得到证实。虽然PLP对所有这四种疾病都有益，但PNPO患者通常对吡哆醇耐药，需要PLP替代治疗。特别是在新生儿期治疗抵抗性癫痫发作中，必须尽早考虑这些疾病，以防止不可逆转的神经损伤。
