title: Identification of a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism.
abstract: Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT), is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (<25 mg/dL). No S or Z mutation was identified, but sequencing analysis found a homozygous cytosine and adenine (CA) insertion in exon 2 of the SERPINA-1 gene, probably leading to a dysfunctional protein (PI Null/Null). This mutation has not been previously identified. The atypical presentation of the patient, with severe cystic bronchiectasis, highlights AAT deficiency as a differential diagnosis in bronchiectasis. Further, awareness should be raised regarding a possible increased risk of thromboembolism associated with AAT deficiency.
authors.affiliation: Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Milger
authors.affiliation: Institute of Laboratory Medicine, University of Munich, Munich, Germany.
authors.forename: Lesca Miriam
authors.initials: LM
authors.lastname: Holdt
authors.affiliation: Institute of Laboratory Medicine, University of Munich, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.affiliation: Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: Rudolf Maria
authors.initials: RM
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behr
authors.affiliation: Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Kneidinger
mesh_terms: D000328:Adult; D001987:Bronchiectasis / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000628:therapy; D004252:DNA Mutational Analysis; D019075:Electrophoresis, Capillary; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D016254:Mutagenesis, Insertional; D010641:Phenotype; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000628:therapy; D012307:Risk Factors; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000628:therapy
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin
keywords: SERPINA-1 mutation; alpha-1 antitrypsin deficiency; bronchiectasis; pulmonary embolism