Annunziata Anna, Ferrarotti Ilaria, Coppola Antonietta, Lanza Maurizia, Imitazione Pasquale, Spinelli Sara, Micco Pierpaolo Di, Fiorentino Giuseppe
Unit of Respiratory Physiopathology, Department of Critic Area, Monaldi Hospital, 80131 Naples, Italy.
Center for Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Pneumology Unit, Department of Internal Medicine and Therapeutics, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
J Clin Med. 2021 Apr 7;10(8):1546. doi: 10.3390/jcm10081546.
Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years' duration. The purpose of this study was to evaluate the incidence of alpha-1 antitrypsin deficiency in patients with the chronic pulmonary disease after a thorough screening in the city of Naples in southern Italy.
Two hundred patients suffering from respiratory pathology (chronic obstructive pulmonary disease (COPD), emphysema, asthma, or bronchiectasis) were examined and evaluated in our outpatients' clinic and tested for serum levels of AAT. Patients who had a respiratory disease suspected of AATD and/or serum AAT < 120 mg/dL underwent genetic testing. Genetic screening was performed on samples from 141 patients.
A total of 36 patients had an intermediate deficiency of AAT levels. Among them, 8 were PIMZ, 6 were PIMS and 22 had rare pathological mutations. Five patients had a severe AATD, all were composite heterozygous with S or Z allele, while the other allele had a rare pathological mutation.
The incidence of genetic defects as AATD in the population of patients affected by chronic respiratory disorders is always a matter of discussion because of the frequent interaction between genes and environmental causes. In our series, numerous rare variants and compound heterozygosity have been described. No homozygous patients have been described. The present is one of few studies available on the incidence of rare variants in the geographic area of the city of Naples. So, our results could be considered interesting not only to know the incidence of AATD and its related rare mutations but also to support early diagnosis and treatments for patients with chronic pulmonary disease and frequent exacerbation and to fight the association with environmental causes of pulmonary damages as smoking.
α-1抗胰蛋白酶缺乏症（AATD）是一种与严重蛋白质缺乏患者的多种呼吸系统疾病相关的遗传疾病。AATD常常诊断较晚或诊断不足。诊断通常发生在患有慢性阻塞性肺疾病和肺气肿的患者中，这些患者频繁发作且病程超过十年。本研究的目的是在意大利南部那不勒斯市进行全面筛查后，评估慢性肺病患者中α-1抗胰蛋白酶缺乏症的发病率。
在我们的门诊诊所对200名患有呼吸系统疾病（慢性阻塞性肺疾病（COPD）、肺气肿、哮喘或支气管扩张）的患者进行了检查和评估，并检测了血清AAT水平。怀疑患有AATD和/或血清AAT<120mg/dL的呼吸系统疾病患者接受了基因检测。对141名患者的样本进行了基因筛查。
共有36名患者AAT水平中度缺乏。其中，8名是PIMZ，6名是PIMS，22名有罕见的病理突变。5名患者患有严重的AATD，均为S或Z等位基因的复合杂合子，而另一个等位基因有罕见的病理突变。
由于基因与环境因素之间频繁相互作用，在慢性呼吸系统疾病患者群体中，作为AATD的遗传缺陷发病率一直是一个有争议的问题。在我们的系列研究中，描述了许多罕见变异和复合杂合性。未描述纯合子患者。本研究是那不勒斯市地理区域内关于罕见变异发病率的少数可用研究之一。因此，我们的结果不仅对于了解AATD的发病率及其相关罕见突变，而且对于支持慢性肺病和频繁发作患者的早期诊断和治疗以及对抗与吸烟等肺部损伤环境因素的关联都可能被认为是有趣的。
