Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child
Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child
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DOI：
10.1159/000465520
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发表时间：
2017-01-01
影响因子：
3.2
通讯作者：
Mendonca, Berenice Bilharinho
中科院分区：
文献类型：
--
作者：
Barisson Villares Fragoso, Maria Candida;de Albuquerque Albuquerque, Edoarda Vasco;Mendonca, Berenice Bilharinho
前言：AAA综合征(AAAS)是一种罕见的常染色体隐性遗传病，以软化、失弛缓症、抗ACTH肾上腺皮质功能不全、自主神经功能障碍和进行性神经变性为特征。患者体外成纤维细胞中显示的氧化应激增加，可能是一种中心疾病机制。N-乙酰半胱氨酸保护与氧化应激增加相关的肾损伤患者的肾功能，并提高体外AAAS基因敲除的肾上腺细胞的活性。患者和结果：一名被诊断为AAAS的男孩表现为身材矮小，体内氧化应激增加，评估方法是作为脂质过氧化标志的硫代巴比妥酸反应物质(TBARS)增加，以及低密度脂蛋白(LDL)对氧化的敏感性和高密度脂蛋白(HDL)防止氧化的能力。在AAAS中发现了一个纯合子错义胚系突变(c.523G>；T，p.Val175Phe)。N-乙酰半胱氨酸(600毫克口服，每天两次)可降低氧化应激，但不会改变患者的生长模式。结论：首次报道了AAAS患者体内氧化应激增加。N-乙酰半胱氨酸能降低总胆红素受体水平，降低低密度脂蛋白氧化敏感性，提高高密度脂蛋白的抗氧化作用。应评估抗氧化剂治疗的长期效果，以确定对防止AAAS退变过程的真正益处。(C)2017年S.Karger AG，巴塞尔
Introduction: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients' fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. Patient and Results: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient's growth pattern. Conclusions: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS. (C) 2017 S. Karger AG, Basel