Alpha-1-antitrypsin deficiency

Today in the Airways and Asthma Clinic I had the opportunity to meet a number of patients with known or suspected alpha-1-antitrypsin deficiency - and with this, review some important patterns of inheritance relevant to these patients and their families. Unlike Gregor Mendel's peas, in which one allele (the dominant allele) dictates the phenotype, alpha-1-antitrypsin deficiency displays a pattern of co-dominance, in which both alleles are expressed simultaneously. In the case of alpha-1-antitrypsin deficiency, you can be unaffected (MM) (~98% of the population), a carrier (MZ), or an affected homozygote (ZZ). In patients with the PI**ZZ genotype, there is impairment in both genes responsible for producing the alpha-1-antitrypsin protein, a protein that is important in maintaining normal lung structure and function. As a result we often see early onset emphysema with little-no smoking history, and these patients are at a higher risk for cirrhosis of the liver (where the dysfunctional protein can accumulate). Patient who are carriers (MZ) have one functional allele and one mutant allele - therefore they make a little less of the alpha-1-antitrypsin protein. Today we met a patient who had an abnormal alpha-1-antitrypsin level, with no evidence of respiratory disease; for this reason and given her family history, we suspected she was an MZ genotype, or a carrier. Armed with this knowledge, we were able to advise her on implications for her own health, and provide counseling around approaching genetic testing for her family. I think my last experience providing genetic counseling was during a seminar in my second year of medical school (i.e. not a real clinical encounter), and I was so grateful to be able to step back with my attending staff and consider not only the genetics involved in this particular disorder, but also to appreciate the public perceptions around heritable disease, and approach counseling of this patient in a sensitive, and pragmatic fashion. I was also glad to have the opportunity to build on this counseling throughout the day, meeting other patients with carrier status, and provide insights about their lung and liver health in clear and simple terms. By taking the opportunity early in the day to sit down with my staff, and really understand this disorder, and model discussions around disease and inheritance with patients, I was able to bolster my own learning, and confidence in this particular clinical setting. 

-AS