芳香族L-胺基酸脫羧基酶（AADC）缺乏症孩童進行基因轉殖之圍術期麻醉照護

芳香族L-胺基酸脫羧基酶（aromatic L-amino acid decarboxylase, AADC）缺乏症是罕見的體染色體隱性疾病，導致運動及自律神經系統功能失調（autonomic dysfunction），此疾病的預後差，多數患者在兒童期死亡。目前只有基因治療能大幅度改善疾病症狀，其治療是在腦部基底核（basal ganglia）注射攜帶芳香族L-胺基酸類脫羧基酶基因的腺病毒載體，製造其缺乏的AADC，提高腦中神經傳導物質含量，而達到疾病治療及改善症狀之效果。由於患者無法生成兒茶酚胺類（catecholamines），造成多種神經傳導物質缺乏，在自主神經系統的調節控制有明顯的抑制及障礙，術中可能會產生低血糖、體溫失調等，也會影響血液動力調節功能，術中的止痛藥物及麻醉氣體，也會增加低血壓及心跳徐緩的發生。麻醉前，除了要注意心肺功能的評估，氣道評估也很重要，因為可能伴隨著有構造上的異常，困難維持呼吸道及困難插管的情形，善用各種氣道處理工具，準備相關設備及計畫以確保氣道安全，上述情形也使得麻醉風險提高。日後基因轉殖技術來治療遺傳疾病是一大發展趨勢，藉由此文提供同仁瞭解此疾病之臨床症狀與治療方式，探討AADC缺乏症患者在面臨全身麻醉時可遇到的問題及處理，並希冀能作為日後照顧類似個案時之參考。

關鍵字

芳香族L-胺基酸脫羧基酶缺乏症；基因治療；麻醉照護

並列摘要

AADC deficiency is a rare autosomal recessive disease that may lead to movement disorder and/ or autonomic dysfunction. The prognosis of AADC deficiency patients is poor, and most die in childhood. Gene therapy is the only method currently available to help alleviate related symptoms. Gene therapy involves the injection of adeno-associated viral (AV) vector into the basal ganglia of patients, helping transfer the AADC gene and leading to improved AADC production and higher numbers of neurotransmitters in the brain. Moreover, as patients are unable to produce catecholamine, they may also suffer from a disorder affecting the regulatory control of the autonomic nervous system, resulting in hypoglycemia, which often causes imbalances in thermoregulation and hemodynamic and functional adjustments during surgery. Furthermore, the use of analgesics and inhalational anesthetics increase the risks of hypotension and bradycardia. Thus, in addition to assessing cardiac and respiratory system functions, it is important to evaluate the patient's airway before administering anesthesia, as structural anomalies or other situations may be present that lead to difficulties in tracheal intubation. Various airway tools, anesthesia equipment, and alternative plans should thus be prepared to protect the airway and maintain vital signs. All of the abovementioned issues increase the risks of AADC deficiency patients undergoing general anesthesia. The development of gene transfection for genetic diseases is a future trend. This paper identifies possible problems and related responses in perioperative patient care during gene therapy. The authors hope that these experiences provide references for the administration of AADC and similar gene therapies in the future.

並列關鍵字

aromatic amino acid decarboxylase deficiency ； gene therapy ； anesthesia management

參考文獻

Alfadhel, M., & Kattan, R. (2014). Aromatic amino acid decarboxylase deficiency not responding to pyridoxine and bromocriptine therapy: Case report and review of response to treatment. Journal of Central Nervous System Disease, 6, 1-5. https://doi.org/10.4137/JCNSD.S12938

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Hwu, W. L., Lee, N. C., Chien, Y. H., Muramatsu, S. I., & Ichinose, H. (2013). AADC deficiency: Occurring in humans, modeled in rodents. Advances in Pharmacology, 68, 273–284. https://doi.org/10.1016/B978-0-12-411512-5.00013-0

Hwu, W. L., Muramatsu, S. I., Lee, N. C., Chien, Y. H., Tseng, S. H., Tzen, K. Y., ... Wu, R. M. (2015). An update on gene therapy for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. Molecular Therapy, 23(1, Suppl.), S103. https://doi.org/10.1016/S1525-0016(16)33868-0

Hwu, W. L., Muramatsu, S. I., Tseng, S. H., Tzen, K. Y., Lee, N. C., Chien, Y. H., ... Wu, R. M. (2012). Gene therapy for aromatic L-amino acid decarboxylase deficiency. Science Translational Medicine, 4(134), 61. https://doi.org/10.1126/scitranslmed.3003640

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芳香族L-胺基酸脫羧基酶（AADC）缺乏症孩童進行基因轉殖之圍術期麻醉照護

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