Facilitating the Laboratory Diagnosis of α1-Antitrypsin Deficiency

Abstract

α(1)-Antitrypsin (AAT) deficiency leads to deterioration of the lungs that can be prevented with diagnosis and treatment. Isoelectric focusing (IEF) electrophoresis is the current biochemical gold standard for detecting AAT deficiency variants but involves complex interpretation. Variant AAT samples were collected over a 2-year period. Stability of AAT for phenotype determination was assessed in whole blood, dried blood spots, and dried serum spots. A compendium displaying 13 common and 5 rare AAT phenotypes was created, and a detailed methodology describing how to recognize AAT banding patterns and interpret a rare phenotype accompanied these visual data. AAT was stable for IEF phenotype analysis for at least 1 week in whole blood and for 24 hours on dried serum spots. In conclusion, a reference compendium of known AAT phenotypes was established that can serve as a resource for interpreting AAT phenotypes.

Diagnosing α1-antitrypsin deficiency: how to improve the current algorithm

“…In Ireland we have screened >12 000 patients and found that >29% have at least one abnormal AAT allele and ∼1.4% have a rare mutation (table 3). It is important that we are able to identify these rarer variants since they may be associated with lung or lung and liver disease [7,16].…”

Diagnosis of alpha-1 antitrypsin deficiency: Modalities, indications and diagnosis strategy

“…However, it may be difficult to interpret the profiles obtained and some expertise may be required. Nevertheless, various recently published studies help identifying the complex phenotypic profiles [19,37].…”

“…Cependant, l'interprétation des profils obtenus peut s'avérer délicate et nécessiter une certaine expérience. Néanmoins, différents travaux publiés récem-ment aident à l'identification des profils phénotypiques parfois complexes[19,37].Cette technique permet d'identifier non seulement les variants les plus courants PI M, PI S, PI Z mais aussi d'autres variants plus rares. Toutefois, les variants PI M déficitaires et les variants null ne peuvent être caractérisés par cette approche méthodologique et leur identification nécessite le recours au génotypage par séquençage.…”

The DIAGNOSTIC AND CLINICAL VALUE OF DETERMINATION OF Α1-Antitrypsin PHENOTYPE IN SYSTEMIC VASCULITIDES

“…2 α1-Antitrypsin (α1-AT) deficiency is a common genetic disorder characterized by low serum α1-AT levels and a clinical manifestation of pulmonary emphysema and liver disease. In addition to its classical manifestations, α1-AT deficiency frequently accompanies granulomatosis with polyangiitis (GPA); in this case the role of α1-AT deficiency in the clinical course of GPA has not been defined.…”

“…В по-пуляции преобладает PiM-аллель, обеспечивающая со-хранную функцию А1АТ, а фенотип молекулы А1АТ у здо-рового человека обозначается PiMM. Некоторые генети-ческие варианты А1АТ, например PiZ и PiS, приводят к его дефициту [2]. Для скрининга дефицита А1АТ целе-сообразно определение именно фенотипа А1АТ, а не его концентрации, которая нередко остается в пределах ре-ференсных значений [3].…”