Detection of alpha-1 antitrypsin deficiency: the past, present and future

Abstract

Background: Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development. Improving the detection rate for AATD is therefore a high priority for the Alpha-1 Foundation. A workshop was held on June 23, 2019 in Orlando, Florida during which stakeholders from the research, pharmaceutical, and patient communities focused on the topic of alpha-1 antitrypsin deficiency detection. Results: A variety of detection strategies have been explored in the past and new approaches are emerging as technology advances. Targeted detection includes patients with chronic obstructive pulmonary disease, unexplained chronic liver disease, and family members of affected individuals. Newborn screening, electronic medical record data mining, and direct-to-consumer testing remain options for future detection strategies. Conclusion: These meeting proceedings can serve as a basis for innovative approaches to the detection of alpha-1 antitrypsin deficiency.

The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry

“…It is assumed that AATD is an underdiagnosed disease and population-wide screening programmes would probably reveal many asymptomatic or presymptomatic carriers of typical AATD phenotypes with an expected ratio of one in 3,500 screened persons [4,5,30,31]. However, recent evidence suggests that even many AATD patients with symptomatic lung disease are not correctly identified: Only 6% of the Pi*ZZ carriers in a large biobank were diagnosed although they had an eightfold increased risk of COPD, a sevenfold increased risk of emphysema and 2.4-fold increased risk of mortality, compared to wild-type (Pi*MM) [32].…”

“…One reason might be the low awareness of physicians and consequently low adherence to the guidelines [30,33]. Except earlier onset in some cases, the clinical presentation of COPD patients with or without AATD is similar which might be another obstacle for timely diagnosis [31,33].…”

“…Furthermore, patients who are diagnosed immediately after developing symptoms could profit from earlier initiation of intravenous augmentation therapy which decelerates the loss of lung density and is associated with improved survival [35][36][37][38]. Recruiting of study participants for clinical trials in AATD is challenging due to a low number of identified AATD patients, even symptomatic ones [1,31]. Intensified screening efforts would raise the number of potential participants and, thus, help researchers to improve feasibility and significance of clinical trials in AATD [31].…”

Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil

“…A amostra de swab bucal permanece estável por dois meses. (54) O teste de genotipagem A1AT oferece cobertura mundial incluindo algumas das mais comuns variantes alélicas raras (Mmalton, Mprocida, I, F) e ultrarraras entre as 14 variantes alélicas selecionadas. (55) A ausência de qualquer uma das 14 mutações no teste é relatada como "variante não detectada" e sugere que o genótipo pode ser o Pi*MM (genótipo normal).…”

Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews

“…Recent reviews of AATD have focused on the epidemiology and distribution of genetic variants, disease screening, diagnosis and care, as well as AAT therapy [2,3,[15][16][17][18][19]. In contrast, comprehensive reviews that assess the burden of AATD on patients, caregivers and healthcare systems are lacking.…”