de Seynes Camille, Ged C, de Verneuil H, Chollet N, Balduyck M, Raherison C
Department of Respiratory Diseases, Bordeaux University, France.
Department of Biochemistry and Molecular Biology, Bordeaux University, France.
Respir Med Case Rep. 2016 Nov 18;20:64-67. doi: 10.1016/j.rmcr.2016.11.008. eCollection 2017.
Alpha-1-antitrypsin deficiency (A1ATD) is a genetic condition caused by SERPINA1 mutations, which results into decreased protease inhibitor activity in the serum and predisposes to emphysema and/or to liver disease due to accumulation of the abnormal protein in the hepatic cells. In most cases the clinical manifestations of A1ATD are associated with PIZZ (p.Glu366Lys; p.Glu366Lys (p.Glu342Lys; p.Glu342Lys)) or PISZ (p.Glu288Val; p.Glu366Lys (p.Glu264Val; p.Glu342Lys)) genotype, less frequently, deficient or null alleles may be present in compound heterozygous or homozygous A1AT deficient patients. We report the identification of a novel alpha1-antitrypsin variant in a 64-year old woman presenting with dyspnea on exertion. Imaging revealed bilateral bronchiectasis associated with moderate panacinar emphysema. The pulmonary function tests (PFTs) were subnormal but hypoxemia was noticed and A1AT quantitative analysis revealed a severe deficiency. DNA sequencing showed compound heterozygosity for the PIZ variant and a novel missense variant p.Phe232Leu (p.Phe208Leu). No specific treatment was proposed since PFTs were within the normal range at this stage of the disease. Close follow-up of pulmonary and hepatic parameters was recommended.
α1抗胰蛋白酶缺乏症（A1ATD）是一种由SERPINA1基因突变引起的遗传疾病，该突变导致血清中蛋白酶抑制剂活性降低，并由于异常蛋白在肝细胞中蓄积而易患肺气肿和/或肝病。在大多数情况下，A1ATD的临床表现与PIZZ（p.Glu366Lys；p.Glu366Lys（p.Glu342Lys；p.Glu342Lys））或PISZ（p.Glu288Val；p.Glu366Lys（p.Glu264Val；p.Glu342Lys））基因型相关，较少见的是，在复合杂合子或纯合子A1AT缺乏患者中可能存在缺陷或无效等位基因。我们报告了在一名64岁出现劳力性呼吸困难的女性中鉴定出一种新型α1抗胰蛋白酶变体。影像学显示双侧支气管扩张伴中度全腺泡型肺气肿。肺功能测试（PFT）低于正常水平，但发现有低氧血症，A1AT定量分析显示严重缺乏。DNA测序显示PIZ变体与一种新型错义变体p.Phe232Leu（p.Phe208Leu）呈复合杂合状态。由于在疾病的这个阶段PFT在正常范围内，因此未提出具体治疗方案。建议密切随访肺部和肝脏参数。
