Alpha-1 Antitrypsin Deficiency: Principles of Care

Abstract

Alpha-1 antitrypsin deficiency is an autosomal co-dominant inherited disorder that results in decreased circulating levels of alpha-1 antitrypsin (also known as alpha-1 proteinase inhibitor) and predisposes affected individuals to early onset lung and liver disease. There is currently no cure for alpha-1 antitrypsin deficiency. However, appropriate treatment and a high standard of clinical care can prevent patients from being seriously affected and having to undergo major medical interventions, such as organ transplantation. Beyond managing the symptoms associated with alpha-1 antitrypsin deficiency, alpha-1 proteinase inhibitor therapy is the only treatment for the condition’s underlying cause. Early diagnosis is important to ensure efficient therapeutic strategies and to minimize further deterioration of lung function. alpha-1 antitrypsin deficiency is under diagnosed globally, partly because the disease has no unique presenting symptoms. This document was prepared by a Portuguese multidisciplinary group and it aims to set out comprehensive principles of care for Alpha-1 antitrypsin deficiency. These include the importance of registries, the need for clinical research, the need for consistent recommendations (regarding diagnosis, treatment and monitoring), the role of reference centres, the requirement for sustained access to treatment, diagnostic and support services, and the role of patient organizations.

Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency

“…Even though it is acknowledged that early identification of AATD enables those individuals to implement preventive therapeutic or lifestyle measures which may protect lung and/or liver damage, thus delaying the onset of disease, some ethical concerns may be raised. 4,11,19 Prenatal diagnosis may be performed by means of an amniocentesis or chorion villi biopsy, which subsequently undergo a DNA analysis (genotyping). 19 Importantly, the collection of either of these samples is invasive and may put the viability of approximately 1% of pregnancies at risk.…”

“…Additionally, the early detection of AATD allows the implementation of preventive measures, namely avoidance of smoking and of environmental risks, compliance with vaccination, physical exercise, adequate follow-up and eventual treatment in the early stages of the disease, which are widely recognized as being of particular importance to prevent and/ or avoid the progression of pulmonary disease. 3,4,11,21 Therefore, and because non-invasive methods are available, the experts also recommend neonatal diagnosis for those individuals who descend from couples where both parents carry an AAT pathogenic variant. Impact of COVID-19 on AATD patients AATD has been proposed as a risk factor for COVID-19, not only because it may facilitate the entry of the virus into host cells, but also due to an increased likelihood of lung injury and to a possible risk of developing a coagulation disorder.…”

“…2,3 As for the prevalence of AATD, this condition is estimated to represent up to 5% of COPD cases. 11 Importantly, although epidemiological data are scarce in both Europe and the United States, the prevalence of AATD can be compared with that of cystic fibrosis, impacting 1:2000 to 1:5000 people. [3][4][5]12 Nevertheless, and in order to contribute to a better awareness of AATD and to accurately record the real impact of this genetic disorder, efforts are being made and the Portuguese medical community is currently registering their patients on the pan-European Alpha-1 Research Collaboration platform (EARCO), 13 which is supported by the European Respiratory Society and the Portuguese Society of Pulmonology.…”