Folinic Acid-Responsive Seizures Are Identical to Pyridoxine-Dependent Epilepsy
Folinic Acid-Responsive Seizures Are Identical to Pyridoxine-Dependent Epilepsy
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DOI：
10.1002/ana.21568
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发表时间：
2009-05-01
影响因子：
11.2
通讯作者：
Jakobs, Cornelis
中科院分区：
文献类型：
--
作者：
Gallagher, Renata C.;Van Hove, Johan L. K.;Jakobs, Cornelis
目的：亚叶酸反应性癫痫和吡哆醇依赖性癫痫是新生儿癫痫性脑病的两种可治疗的病因。前者通过脑脊液（CSF）单胺代谢物分析的特征峰进行诊断;其遗传基础仍然难以捉摸。后者是由于α-氨基己二酸半醛（α-AASA）脱氢酶缺乏，与ALDH7A1（antiquitin）基因的致病性突变有关。我们报告两个病人的脑脊液显示标志物亚叶酸反应性癫痫发作，但谁回应吡哆醇临床。我们进行了遗传和生化测试，从这些患者的样本，和其他7人，以确定这两个disorders.Methods之间的关系：CSF样本进行了分析，α-AASA和哌啶酸的存在。进行ALDH7A1基因的DNA测序。结果如下：本文报告的2例患者均存在CSF α-AASA、CSF哌啶酸升高，以及ALDH7A1基因中已知或可能的致病性突变，与α-AASA脱氢酶缺乏症一致。对来自其他七个被诊断为亚叶酸反应性癫痫发作的匿名个体的CSF样本的分析显示了类似的结果。解释：这些结果表明，亚叶酸反应性癫痫发作是由于α-AASA脱氢酶缺乏和ALDH7A1基因突变所致。因此，亚叶酸反应性癫痫发作与吡哆醇依赖性癫痫的主要形式相同。我们建议对α-AASA脱氢酶缺乏症患者同时考虑吡哆醇和亚叶酸治疗，并考虑限制赖氨酸饮食。对新生儿癫痫性脑病患者以及迟发性癫痫患者的评估应包括尿液中α-AASA的测量，以确定这种可能未被诊断和可治疗的疾病。
Objective: Folinic acid-responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid-responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders.Methods: CSF samples were analyzed for the presence of alpha-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Results: Both patients reported here had increased CSF alpha-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with alpha-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid-responsive seizures showed similar results.Interpretation: These results demonstrate that folinic acid-responsive seizures are due to alpha-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid-responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with alpha-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of alpha-AASA in urine to identify this likely underdiagnosed and treatable disorder.