尽管接受了吡哆醇治疗,但由于α-氨基己二酸半醛脱氢酶缺乏症(PDE-ALDH7A1)而导致的吡哆醇依赖性癫痫患者中有75%患有智力发育障碍。辅助赖氨酸减少疗法(LRT),旨在降低推定的神经毒性代谢物,与认知结果的改善有关。然而,可能是由于治疗的时机,并非所有患者都有正常的智力功能。
这次回顾展,多中心队列研究评估了吡哆醇单药治疗和吡哆醇辅助LRT治疗时机对神经发育结局的影响.已确诊的PDE-ALDH7A1患者至少有一个PDE-ALDH7A1的兄弟姐妹,并且在治疗开始时年龄存在差异,这些患者符合资格,并通过国际PDE注册中心进行鉴定。导致18个家庭的37名患者。治疗方案为10个家庭的吡哆醇单药治疗,其他8个家庭的吡哆醇和辅助LRT治疗。主要终点是标准化和临床评估的神经发育结果。临床神经发育状态在七个领域进行了主观评估:整体神经发育,语音/语言,认知,精细和粗大的运动技能,日常生活活动和行为/精神异常。
在临床评估的精细运动技能领域,接受吡哆醇单药治疗的早期兄弟姐妹中,大多数比接受晚期治疗的兄弟姐妹表现更好。对于吡哆醇和附属轻轨的兄弟姐妹,大多数早期治疗的兄弟姐妹在临床评估的整体神经发育方面表现更好,认知,和行为/精神病学。在所有领域中,总队列的14%被评估为正常。
吡哆醇和辅助LRT的早期治疗可能对神经发育结果有益。在评估更广泛的神经发育评估时,实际减损率可能高于文献报道的75%。
在PDE-ALDH7A1患者中早期启动赖氨酸减少疗法辅助吡哆醇治疗可能导致神经发育结果的改善。
Seventy-five percent of patients with pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency (PDE-ALDH7A1) suffer intellectual developmental disability despite pyridoxine treatment. Adjunct lysine reduction therapies (LRT), aimed at lowering putative neurotoxic metabolites, are associated with improved cognitive outcomes. However, possibly due to timing of treatment, not all patients have normal intellectual function.
This retrospective, multi-center cohort study evaluated the effect of timing of pyridoxine monotherapy and pyridoxine with adjunct LRT on neurodevelopmental outcome. Patients with confirmed PDE-ALDH7A1 with at least one sibling with PDE-ALDH7A1 and a difference in age at treatment initiation were eligible and identified via the international PDE registry, resulting in thirty-seven patients of 18 families. Treatment regimen was pyridoxine monotherapy in ten families and pyridoxine with adjunct LRT in the other eight. Primary endpoints were standardized and clinically assessed neurodevelopmental outcomes. Clinical neurodevelopmental status was subjectively assessed over seven domains: overall neurodevelopment, speech/language, cognition, fine and gross motor skills, activities of daily living and behavioral/psychiatric abnormalities.
The majority of early treated siblings on pyridoxine monotherapy performed better than their late treated siblings on the clinically assessed domain of fine motor skills. For siblings on pyridoxine and adjunct LRT, the majority of early treated siblings performed better on clinically assessed overall neurodevelopment, cognition, and behavior/psychiatry. Fourteen percent of the total cohort was assessed as normal on all domains.
Early treatment with pyridoxine and adjunct LRT may be beneficial for neurodevelopmental outcome. When evaluating a more extensive neurodevelopmental assessment, the actual impairment rate may be higher than the 75% reported in literature.
Early initiation of lysine reduction therapies adjunct to pyridoxine treatment in patients with PDE-ALDH7A1 may result in an improved neurodevelopmental outcome.