title: Laboratory testing of individuals with severe alpha1-antitrypsin deficiency in three European centres.
abstract: alpha(1)-Antitrypsin (AT) deficiency is a hereditary disorder that may lead to early-onset emphysema, and chronic liver disease later in life. Although there are validated methods for testing, the vast majority of alpha(1)-AT-deficient individuals remain undiagnosed. Recommendations have been published for the testing and diagnosis of alpha( 1)-AT deficiency; however, guidelines on best practice are not well established. In our article, we review the developments in diagnostic techniques that have taken place in recent years, and describe the practices used in our three European centres. The determination of the level of alpha(1)-AT and genotyping are reported as the main diagnostic steps, whereas isoelectric focusing (also referred to as phenotyping) is reserved for confirmatory analysis. The following recommendations for best practice are put forward: detection of all PiZZ and other severe deficiency individuals; automated genotyping; preparation of reference standards; quality control programmes; development of standard operating procedure documents; and standardised methods for the collection of dried blood samples. Closer cooperation between laboratories and the sharing of knowledge are recommended, with the objectives of improving the efficiency of the diagnosis of severe alpha(1)-AT deficiency, increasing the numbers of individuals who are detected with the disorder, and assisting the establishment of new patient identification programmes.
authors.affiliation: Fundació Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Respiratorias, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Miravitlles
authors.forename: C
authors.initials: C
authors.lastname: Herr
authors.forename: I
authors.initials: I
authors.lastname: Ferrarotti
authors.forename: R
authors.initials: R
authors.lastname: Jardi
authors.forename: F
authors.initials: F
authors.lastname: Rodriguez-Frias
authors.forename: M
authors.initials: M
authors.lastname: Luisetti
authors.forename: R
authors.initials: R
authors.lastname: Bals
mesh_terms: D000465:Algorithms; D001800:Blood Specimen Collection; D002908:Chronic Disease; D005820:Genetic Testing / Q000379:methods*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007525:Isoelectric Focusing; D007558:Italy / Q000453:epidemiology; D008107:Liver Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D017410:Practice Guidelines as Topic; D011656:Pulmonary Emphysema / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000453:epidemiology / Q000235:genetics
chemical_list: D000515:alpha 1-Antitrypsin