Tural Önür Seda, Karaca Şenkal Kardelen
Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, İstanbul, Turkiye.
Respir Med Case Rep. 2024 Jul 5;51:102084. doi: 10.1016/j.rmcr.2024.102084. eCollection 2024.
Alpha-1 antitrypsin (AAT) deficiency, characterized by reduced synthesis of a serine protease inhibitor in liver cells, has been recognized to contribute to the development of emphysema and liver disease. Additional clinical manifestations encompassing respiratory disorders and dermatological issues have also been documented.
A 56-year-old male patient presented with dyspnea. Despite being a non-smoker, he had a diagnosis of chronic obstructive pulmonary disease (COPD) five years ago. Utilizing inhaled corticosteroids (ICSs) - long-acting β2-agonists (LABAs)- long-acting muscarinic antagonists (LAMAs) inhalers, the patient's medical treatment had ceased for the past four months due to inhaler depletion. High-resolution thoracic computed tomography unveiled bilateral emphysematous regions, predominantly located in the lower pulmonary lobes. In light of the absence of smoking history, the suspicion of AAT deficiency was raised, prompting the assessment of serum AAT levels. Subsequent analysis indicated diminished AAT levels, prompting the collection of a dried blood sample for genetic evaluation. Genomic DNA amplification was performed using polymerase chain reaction (PCR), succeeded by allele-specific hybridization via Luminex XMAP Technology. This analysis disclosed a Q0amersfoort (Exon 2 Y160TAC > Ter TAG) (+/+) variant linked with AAT deficiency, originating from a frame-shift mutation that triggers a null (Q0amersfoort) stop codon.
The presentation of COPD-related emphysema in a non-smoker underscores the necessity to consider AAT deficiency in the differential diagnosis.
α-1抗胰蛋白酶（AAT）缺乏症的特征是肝细胞中丝氨酸蛋白酶抑制剂的合成减少，已知其会导致肺气肿和肝病的发展。还记录了包括呼吸系统疾病和皮肤病问题在内的其他临床表现。
一名56岁男性患者出现呼吸困难。尽管他不吸烟，但五年前被诊断为慢性阻塞性肺疾病（COPD）。患者使用吸入性糖皮质激素（ICS）-长效β2受体激动剂（LABA）-长效毒蕈碱拮抗剂（LAMA）吸入器进行治疗，但由于吸入器耗尽，在过去四个月中停止了治疗。高分辨率胸部计算机断层扫描显示双侧肺气肿区域，主要位于下肺叶。鉴于患者无吸烟史，怀疑为AAT缺乏症，于是对血清AAT水平进行了评估。随后的分析表明AAT水平降低，因此采集了一份干血样本进行基因评估。使用聚合酶链反应（PCR）进行基因组DNA扩增，随后通过Luminex XMAP技术进行等位基因特异性杂交。该分析揭示了一种与AAT缺乏症相关的Q0amersfoort（外显子2 Y160TAC > Ter TAG）（+/+）变体，它源自一个导致无效（Q0amersfoort）终止密码子的移码突变。
非吸烟者出现与COPD相关的肺气肿突出了在鉴别诊断中考虑AAT缺乏症的必要性。
