One of the most progressive evolutions of medicine in recent decades is the implementation of screening programs to detect the presence of a disease even before symptoms arise. Examples of common screening programs found in most Western countries are breast cancer screening for women and colorectal cancer screening for men.
Indeed, the screening for certain diseases has become as routine as going to the dentist, except that it usually occurs only once every few years. Importantly, the practice of screening for certain diseases has made a sizeable impact on patient survival. Needless to say, cancer detected in its infancy is far easier to treat than when it has metastasized.
However, when governments commit to implementing screening programs, they are also committing a certain percentage of public funds for that purpose – most likely indefinitely. In other words, once a screening program is implemented, it will be nearly impossible to justify withdrawing it. This gives governments pause when deciding whether to implement new publicly funded screening programs, even if they are thoroughly evidence-based.
A researcher from the Medical University of South Carolina in Charleston, Kimberly E. Foil, conducted a review of what we currently know about the variants of SERPINA1 in alpha-1 antitrypsin deficiency (AATD) and the challenges of implementing screening programs for the disease. We will discuss some of her findings in this article.
Screening for AATD
Most of the epidemiological data we have on AATD comes from Western countries, and the lack of adequate epidemiological data from other parts of the world means that we only know half the story. Even when epidemiological studies are conducted, they tend to target communities in which there are reasons to suspect enhanced levels of AATD, for example, due to relatives of a proband or early-onset chronic obstructive pulmonary disease (COPD).
Although it makes sense to screen for AATD in patients with respiratory problems such as COPD and emphysema, this approach does mean that we will likely miss out on asymptomatic or presymptomatic individuals. Hence, epidemiological studies are still unlikely to give us a complete picture of AATD in the community.
Read more about AATD diagnosis
However, in 1976, Swedish researchers screened 200,000 infants for AATD – the largest study of its kind. “Studies such as this are informative but can be prohibitively expensive and therefore, population-wide screening has seen limited application,” the author wrote. Indeed, “prohibitively expensive” is, unfortunately, a key reason why more screening tests are not carried out, even for other diseases. In addition, population-wide screening comes with its own baggage, for example, potential gender discrimination and potentially negative psychological impact.
In the United States, physicians have the option of ordering AATD tests through institutional or for-profit laboratories. In addition, the Alpha-1 Foundation offers AATD testing that is free and confidential. However, what we see in the United States, and indeed, many Western countries, is the rise of commercial genetic screening, such as the popular and FDA-approved 23andMe. This allows anyone to request genetic testing for a fee. Recently, AATD has been included in genomic health screens. Hopefully, widespread testing for AATD on a voluntary basis will enrich our understanding of the true scale of the disease in a given population.
SERPINA1 alleles are codominantly expressed, and 1 of each parent’s 2 SERPINA1 alleles is passed to their offspring. This means that if a child is heterozygous for the pathogenic SERPINA1 allele, half of the child’s AAT production will be normal while the other half is abnormal. If one parent is heterozygous for the pathogenic SERPINA1 allele and the other is an unaffected noncarrier, the child has a 50% chance of being heterozygous and a 50% chance of being an unaffected noncarrier.
In other words, basic genetic rules apply. However, more pertinent to our discussion is how genetic counseling should be carried out if any parent is found to be a carrier of pathogenic SERPINA1 alleles. AATD testing should be offered to family members of patients confirmed to have AATD – children, siblings, and even extended family. However, genetic testing of family members comes with its own set of ethical challenges, and physicians will be wise to offer some form of genetic counseling prior to any decision regarding testing.
Read more about AATD patient education
For example, genetic testing in children is controversial since they are unable to give informed consent, but an early diagnosis can allow physicians to monitor disease progression more closely in the years ahead. However, even in adults, a positive AATD test can have huge implications, including stress and anxiety as well as affecting insurance eligibility and cost. This is why it is helpful for physicians to first help patients understand how AATD is inherited, the likelihood of family members being affected, and the help and support that is available should a diagnosis of AATD be made.
In an article like this where the sole focus is AATD, it is clear that much needs to be done to improve access to screening and genetic counseling. However, AATD remains a relatively rare disease, and in the overall scheme of things, it is but a drop in the ocean. This is not to minimize the suffering of patients with AATD, but to help us gain some perspective as to why barriers to publicly funded population-wide screening remain so high. With further research, we may yet arrive at a solution that is fair, affordable, and effective.
Foil KE. Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency. Ther Adv Chronic Dis. 2021;12_suppl:20406223211015954. doi:10.1177/20406223211015954
Strange C, Moseley MA, Jones Y, Schwarz L, Xie L, Brantly ML. Genetic testing of minors for alpha1-antitrypsin deficiency. Arch Pediatr Adolesc Med. 2006;160(5):531-534. doi:10.1001/archpedi.160.5.531