探討AADC缺乏症患者接受基因治療後之睡眠呼吸變化

Abstract

背景：AADC缺乏症患者因多巴胺與血清素的製造異常，導致睡眠週期紊亂、睡眠時易有不自主運動、呼吸型態不穩定或睡眠呼吸中止等問題。且因患者睡眠時咽喉部肌肉張力低下，易發生阻塞型睡眠呼吸中止症。近年來，AADC缺乏症患者接受基因治療後，病情皆有明顯進步，且病患父母也稱患童睡眠因此得到改善。本研究旨在探討基因治療後患者的睡眠呼吸變化。 方法：本研究納入了10位AADC缺乏症患者，接受基因治療時平均年紀為4.35 ± 0.81 歲(平均值 ± 標準差)（範圍：1.67-8.48歲；男性為5位，女性為5位）。本研究藉由回溯性的方式，分析基因治療前後的24小時血氧脈搏記錄。檢查於基因治療前執行一次，並於基因治療後第6個月與第12個月各執行一次，持續追蹤一年。 結果：經研究分析後發現，AADC缺乏症患者在經過基因治療後12個月，其血氧飽和度指數與睡眠呼吸中止嚴重度皆從重度顯著下降至輕-中度；除此之外，血氧濃度低於90%的時間也有顯著性的減少。在經過基因治療後6個月，發生呼吸事件的總時間、每次發生呼吸事件的平均時間，以及發生血氧低於90%的呼吸事件次數都有顯著改善。 結論：AADC缺乏症患者在經過基因治療後，睡眠呼吸中止的嚴重程度有明顯進步，且與發生低血氧的相關參數皆有顯著改善。

Background: The patients on Aromatic L-amino acid decarboxylase (AADC) deficiency are showed symptoms of restlessness, anxiety, respiratory distress, sleep apnea and involuntary limbs movement during sleep due to the abnormal dopamine and serotonin level. Besides, they have the problem of extreme hypotonia, the upper airway will collapse at a lower threshold, inducing the obstruction sleep apnea (OSA). Recently, gene therapy was performed on AADC deficiency children. After treatment, they gradually gained some improvement and their parents claimed that the children also slept better. Therefore, the aim of this study was to assess the severity of sleep apnea and the respiratory characteristics on AADC deficiency patients after gene therapy. Materials and methods: We performed a retrospective cohort study of ten AADC deficiency patients (5 boys and 5 girls; mean age 4.35 ± 0.81 years [mean ± SD], range 1.67 to 8.48 years) with gene therapy were studied. Participants completed 24-hour oximetry at the time of pretreatment, 6 months and 12 months after treatment. The follow-up duration was 1 year. Results: In this research, we found that after 12 months of receiving gene therapy, the oximetry score and OSA severity of AADC deficiency patients were significantly decreased from severe to mild-moderate. Time < 90% (min) was improved as well. After 6 months of treatment, Time in Events, Average Event Duration and Events < 90% were clearly reduced. Conclusion: To sum up, OSA severity and some desaturation related characteristics of AADC deficiency patients had a statistically significant improve after gene transfer.