Objective

We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs).

Methods

In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20–30 mg/kg/day) for 1 year, in addition to previous treatment.

Results

All nine enrolled patients (mean age: 66.3 ± 44.3 months) exhibited marked decreases in levels of CD16, a glycosylphosphatidylinositol-anchored protein, on blood granulocytes. The underlying genetic causes of IGDs were PIGO, PIGL, and unknown gene mutations in two, two, and five patients, respectively. Six patients experienced seizures, while all patients presented with developmental delay (mean developmental age: 11.1 ± 8.1 months). Seizure frequencies were markedly (>50%) and drastically (>90%) reduced in three and one patients who experienced seizures, respectively. None of the patients presented with seizure exacerbation. Eight of nine patients exhibited modest improvements in development (P = 0.14). No adverse events were observed except for mild transient diarrhea in one patient.

Conclusion

One year of daily high-dose pyridoxine treatment was effective in the treatment of seizures in more than half of our patients with IGDs and modestly improved development in the majority of them. Moreover, such treatment was reasonably safe. These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm our findings. (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number: UMIN000024185.)

中文翻译：

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高剂量吡哆醇治疗遗传性糖基磷脂酰肌醇缺乏症

客观的

我们旨在评估高剂量吡哆醇治疗癫痫发作的有效性和安全性及其对遗传性糖基磷脂酰肌醇缺乏症 (IGD) 患者发育的影响。

方法

在这项前瞻性开放标签多中心试点研究中，我们招募了使用流式细胞术和/或基因检测诊断为 IGD 的患者。除了先前的治疗外，患者还接受了为期 1 年的口服吡哆醇（20-30 毫克/千克/天）。

结果

所有九名入选患者（平均年龄：66.3 ± 44.3 个月）的血粒细胞 CD16（一种糖基磷脂酰肌醇锚定蛋白）水平显着降低。IGDs 的潜在遗传原因是PIGO , PIGL和未知基因突变分别在两名、两名和五名患者身上发生。6 名患者出现癫痫发作，而所有患者均出现发育迟缓（平均发育年龄：11.1 ± 8.1 个月）。3 名和 1 名癫痫患者的癫痫发作频率分别显着 (>50%) 和急剧 (>90%) 降低。没有患者出现癫痫发作加重。九名患者中有八名在发育方面表现出适度改善（P = 0.14）。除了一名患者出现轻度暂时性腹泻外，未观察到任何不良事件。

结论

一年以上的每日大剂量吡哆醇治疗对我们超过一半的 IGD 患者的癫痫发作有效治疗，并且大多数患者的发育情况略有改善。此外，这种治疗是相当安全的。这些发现表明，高剂量吡哆醇治疗可能对 IGD 患者的癫痫发作有效，尽管需要进一步的研究来证实我们的发现。（大学医院医学信息网临床试验注册[UMIN-CTR]编号：UMIN000024185。）