芳香族L-胺基酸脫羧酵素(AADC)缺乏症基因治療對患母生活品質之影響

The Effect of Gene Therapy for Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency on the Quality of Life of the Mothers

李美欣(Mei-Hsin Li)

指導教授 ： 胡務亮

共同指導教授 ： 簡穎秀 ； 李妮鍾(Ni-Chung Lee)

國立臺灣大學/醫學院/分子醫學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202104354

摘要

芳香族L-胺基酸脫羧酵素(AADC)缺乏症是一罕見疾病，由於疾病症狀的不穩定，常讓照顧者承受著莫大壓力。所幸，在2010年2月臺大醫院透過人道救援的方式以AAV2-hAADC開始進行基因治療，至2020年12月為止已順利完成30名AADC缺乏症患者基因治療。透過基因治療，我們可以看到這群重症的AADC缺乏症患者在透過阿爾伯塔嬰兒動作量表（AIMS）和皮巴迪動作發展量表第二版 (PDMS-2)等量表評估後，顯示粗大動作、精細動作、認知都有顯著改變。但是在臨床試驗中並未詳細評估生活品質的變化，因此本研究將使用問卷調查，了解患者在基因治療介入後生活品質的轉變。
對於患者生活品質的評估，我們設計了一個症狀量表，包含了會影響生活品質的臨床症狀：發作、出汗、體溫等，由於疾病會影響患者情緒，我們請主要照顧者以百分比給患者情緒滿意度評分，以了解在基因治療的介入在生活品質上是否有差別。AADC缺乏症患者主要照顧者多為母親，因此我們同時假設在尚未接受基因治療前，患母在生理健康、心理、社會關係及環境上無法獲得較高的滿足，但在接受基因治療後，隨著孩子的能力增強及穩定，對母親們的生活品質或許會有改善。所以，我們選用臺灣簡明版世界衛生組織生活品質問卷(WHOQOL-BREF)來了解母親的生活品質狀況。
我們發現患者無論在臨床症狀：發作、出汗、體溫及情緒等面向，在治療後都有明顯的改善，因此我們推測患者藉由基因治療有改善生活品質。患者母親的WHOQOL-BREF分析顯示在單題及各範疇的生活品質大都有明顯的改善，表示基因治療帶給病患家庭很實質的幫助。我們也將患母生活品質結果和患者治療前後症狀及運動功能做關聯比較，發現患者治療前之症狀(疾病嚴重度)和患母治療前生活品質有明顯的關聯性，而治療後的分析就沒有甚麼關聯性。
我們相信，這個研究除了讓我們更加了解這項基因治療的效果外，也對臨床試驗的進行有所幫助。

關鍵字

AADC缺乏症 ； 基因治療 ； 生活品質 ； 臺灣簡明版世界衛生組織生活品質問卷

並列摘要

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare disease, and the high instability of patients also give their caretakers a lot of stress. The team at National Taiwan University Hospital started a gene therapy for AADC deficiency in Feb. 2010, and up to now have treated 30 patients. All treated patients were severely affected before gene therapy. After gene therapy, the Alberta Infant Motor Scale (AIMS), Peabody Developmental Motor Scales, Second Edition (PDMS-2), and several other scales all demonstrated significant improvements in both fine and gross motor functions in the patients. However, the changes in life quality after gene therapy were not evaluated in detail in the clinical trial. Therefore, in this study, we designed questionnaires to evaluate the life quality of patients and caretakers before and after gene therapy to supplement the efficacy evaluation of the clinical trials.
We designed a questionnaire to evaluate the symptoms of patients, including oculogyric crisis, body temperature stability, sweating, and mood, that would affect their life quality. Most of the caretakers of patients with AADC deficiency were mothers. We asked the mothers to evaluate those symptoms before and after gene therapy. We also used WHOQOL-BREF to measure the life quality of the mothers, to see if the gene therapy for their children was able to change their own lives.
Our results demonstrated that, in the patients, all symptoms, including OGC, body temperature, sweating, and mood, improved significantly. Therefore, we thought the life quality of these patients would have been improved. WHOQOL-BREF analysis of life quality of the mothers also showed improvements, both in the general and specific domains, suggesting that gene therapy was significant for these families. We further correlated the symptoms or motor function improvement of the patients to the life quality of their mothers. We found a correlation between before-treatment patient symptoms and mother life quality. After gene therapy, the correlation did not exist.
We believe that this study not only increases our understanding of the efficacy of gene therapy for AADC deficiency, but also helps the conduction of clinical trials.

並列關鍵字

AADC deficiency ； gene therapy ； quality of life ； WHOQOL-BREF

參考文獻

世界衛生組織生活品質問卷臺灣版問卷發展小組（2005），臺灣簡明版世界衛生組織生活品質問卷之發展及使用手冊

羅鳳菊（2007），先天性代謝異常疾病患童母親之親職壓力與生活品質之探討，台灣大學分子醫學研究所，碩士論文

詹詩昀 郭惠珍（2010）。芳香族L-胺基酸脫羧酵素缺乏症。民2021年3月25日，取自「罕見遺傳疾病一點通」： http://web.tfrd.org.tw/genehelp/article.html?articleID=Aromatic%2520L-amino%2520acid%2520decarboxylase%2520deficiency%2CAADC submenuIndex=0

Gen Pons, R., B. Ford, et al. (2004). Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. Neurology 62(7), 1058-1065.

Hyland, K. and P. T. Clayton (1990). Aromatic amino acid decarboxylase deficiency in twins. J Inherit Metab Dis 13(3): 301-304.