Ultrastructural Characterization of Genetic Diffuse Lung Diseases in Infants and Children: A Cohort Study and Review
Ultrastructural Characterization of Genetic Diffuse Lung Diseases in Infants and Children: A Cohort Study and Review
复制标题
DOI：
10.3109/01913123.2013.811454
复制
发表时间：
2013-10-01
影响因子：
1
通讯作者：
Danhaive, Olivier
中科院分区：
文献类型：
--
作者：
Citti, Arianna;Peca, Donatella;Danhaive, Olivier
小儿弥漫性肺病是一种罕见的疾病，发病于新生儿期或婴儿期，影像学表现为慢性呼吸道症状和弥漫性间质改变。表面活性剂体内平衡的遗传障碍是主要病因。表面活性剂蛋白B和ABCA3缺乏通常会导致新生儿呼吸衰竭，这通常在几周或几个月内致命。尽管杂合子ABCA3突变携带者大多无症状，但越来越多的证据表明，单等位基因突变可能影响表面活性剂的稳态。表面活性剂蛋白C突变是显性或散发性疾病，可导致从新生儿呼吸窘迫综合征到成人肺纤维化的广泛表现。作者对12名接受临床肺活检的婴儿进行了病理和超微结构研究。1例携带SP-B杂合突变，3例携带SP-C突变，7例携带ABCA3突变（5例双等位基因，2例单等位基因）。光学显微镜使区分与表面活性剂有关的疾病和其他形式的疾病成为可能。其中一个ABCA3单等位基因携带者具有肺泡毛细血管发育不良（肺泡遗传性疾病）和血管发育的形态学特征。一名患者没有表现出表面活性剂相关的异常，但有肺间质性糖原症，这是一种来源不明的发育障碍。电镜显示，所有SP-B、SP-C和ABCA3缺乏的病例均有特殊的板层体异常。此外，作者发现杂合ABCA3突变携带者具有介于纯合携带者和正常受试者之间的中间超微结构表型。肺活检是诊断不明原因弥漫性肺疾病的必要步骤，电子显微镜检查应系统地进行，因为它可以揭示表面活性剂稳态遗传疾病的特定改变。
Pediatric diffuse lung diseases are rare disorders with an onset in the neonatal period or in infancy, characterized by chronic respiratory symptoms and diffuse interstitial changes on imaging studies. Genetic disorders of surfactant homeostasis represent the main etiology. Surfactant protein B and ABCA3 deficiencies typically cause neonatal respiratory failure, which is often lethal within a few weeks or months. Although heterozygous ABCA3 mutation carriers are mostly asymptomatic, there is growing evidence that monoallelic mutations may affect surfactant homeostasis. Surfactant protein C mutations are dominant or sporadic disorders leading to a broad spectrum of manifestations from neonatal respiratory distress syndrome to adult pulmonary fibrosis. The authors performed pathology and ultrastructural studies in 12 infants who underwent clinical lung biopsy. One carried a heterozygous SP-B mutation, 3 carried SP-C mutations, and 7 carried ABCA3 mutations (5 biallelic and 2 monoallelic). Optical microscopy made it possible to distinguish between surfactant-related disorders and other forms. One of the ABCA3 monoallelic carriers had morphological features of alveolar capillary dysplasia, a genetic disorder of lung alveolar, and vascular development. One patient showed no surfactant-related anomalies but had pulmonary interstitial glycogenosis, a developmental disorder of unknown origin. Electron microscopy revealed specific lamellar bodies anomalies in all SP-B, SP-C, and ABCA3 deficiency cases. In addition, the authors showed that heterozygous ABCA3 mutation carriers have an intermediate ultrastructural phenotype between homozygous carriers and normal subjects. Lung biopsy is an essential diagnostic procedure in unexplained diffuse lung disorders, and electron microscopy should be performed systematically, since it may reveal specific alterations in genetic disorders of surfactant homeostasis.