Unidade de Suprarrenal, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Horm Res Paediatr. 2017;88(2):167-171. doi: 10.1159/000465520. Epub 2017 Apr 10.
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.
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.
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.
三 A 综合征（Triple A syndrome，AAAS）是一种罕见的常染色体隐性遗传病，其特征为眼干症、贲门失弛缓症、促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）抵抗性肾上腺功能不全、自主神经功能障碍和进行性神经退行性变。体外研究表明，患者成纤维细胞中氧化应激增加，这可能是该病的主要发病机制。N-乙酰半胱氨酸（N-acetylcysteine，NAC）可保护氧化应激增加相关的肾损伤患者的肾功能，并可提高体外 AAAS 基因敲低的肾上腺细胞的存活率。
一位被诊断为 AAAS 的男孩表现为身材矮小，体内氧化应激增加，其体内的丙二醛（thiobarbituric acid reactive substances，TBARS）水平升高（TBARS 是脂质过氧化的标志物），低密度脂蛋白（low density lipoprotein，LDL）易氧化，高密度脂蛋白（high density lipoprotein，HDL）抗氧化能力下降。该患者存在 AAAS 基因的纯合错义胚系突变（c.523G>T，p.Val175Phe）。每日口服 NAC（600 mg，每日两次）可降低氧化应激，但不能改变患者的生长模式。
本研究首次在 AAAS 患者体内发现氧化应激增加。NAC 可降低 TBARS 水平，降低 LDL 的易氧化性，并提高 HDL 的抗氧化作用。应评估抗氧化治疗的长期效果，以确定其对 AAAS 退行性病变的预防作用。
