Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives.
Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives.
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DOI：
10.2147/jmdh.s295486
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发表时间：
2021
影响因子：
3.3
通讯作者：
Lederman HM
中科院分区：
文献类型：
--
作者：
McGrath-Morrow SA;Rothblum-Oviatt CC;Wright J;Schlechter H;Lefton-Greif MA;Natale VA;Crawford TO;Lederman HM
共济失调毛细血管扩张症是一种罕见的常染色体隐性遗传病，由共济失调毛细血管扩张突变基因（ATM）突变引起。在没有家族史的情况下，a - t的诊断通常要等到孩子长大并出现症状时才会做出。典型的a - t以一系列临床症状为特征，包括进行性共济失调、眼皮肤毛细血管扩张和肺疾病，通常与ATM蛋白缺乏有关。与A-T相关的其他实验室特征包括血清甲胎蛋白（AFP）水平升高和体外暴露于电离辐射时染色体断裂增加。肺症状在人的一生中会不同程度地发生。一些儿童还会有低丙种球蛋白血症和抗体反应受损，需要补充丙种球蛋白。具有半形性ATM突变的人通常被认为患有轻度A-T，并伴有共济失调和神经系统进展，发生在生命后期，免疫系统受损较少。然而，无论是典型的还是轻度的A-T患者，患恶性肿瘤的风险都明显增加。虽然血液恶性肿瘤最常见于生命的前20年，但实体器官恶性肿瘤在成年早期变得越来越常见。随着年龄的增长，神经功能的恶化与吞咽困难、误吸、生长迟缓、行动能力丧失和肺功能下降有关，这些疾病导致预期寿命缩短和生活质量下降。过早死亡通常是由于恶性肿瘤或慢性呼吸功能不全。A-T目前通过支持性护理和对症治疗进行管理。然而，目前的临床试验代表了A-T疾病改善疗法的进展和希望。
Ataxia telangiectasia (A-T) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia mutated (ATM) gene. In the absence of a family history, the diagnosis of A-T is usually not made until the child is older and symptomatic. Classic A-T is characterized by a constellation of clinical symptoms including progressive ataxia, oculocutaneous telangiectasias and sinopulmonary disease and is usually associated with absence of ATM protein. Other laboratory features associated with A-T include elevated serum levels of alpha-fetoprotein (AFP) and increased chromosomal breakage with in vitro exposure to ionizing radiation. Sinopulmonary symptoms can occur to varying degrees across the lifespan. Some children will also have hypogammaglobulinemia and impaired antibody responses requiring supplemental gamma globulin. People with hypomorphic ATM mutations are often considered to have mild A-T with onset of ataxia and neurological progression occurring later in life with less impairment of the immune system. The risk of malignancy, however, is significantly increased in people with either classic or mild A-T. While hematological malignancies are most common in the first two decades of life, solid organ malignancies become increasingly common during young adulthood. Deterioration of neurologic function with age is associated with dysphagia with aspiration, growth faltering, loss of ambulation and decline in pulmonary function, morbidities that contribute to shortened life expectancy and decreased quality of life. Premature death is often due to malignancies or chronic respiratory insufficiency. A-T is currently managed with supportive care and symptomatic treatment. Current clinical trials, however, represent progress and hope towards disease-modifying therapies for A-T.