A1AT Phenotyping Lags Behind, Contributes to Underrecognition of AATD


A Veterans Affairs study finds low alpha-1 antitrypsin phenotyping rates, indicating the need for improved healthcare provider education on AATD.

Zane Elfessi, PharmD | Credit: LinkedIn

Zane Elfessi, PharmD
Credit: LinkedIn

An analysis of data from a Veterans Affairs medical center over 3 years is providing insight into the unmet needs related to education on alpha-1 antitrypsin (A1AT) phenotyping for healthcare providers in the US.

Results of the 30-patient study, suggest phenotyping was performed in less than 50% of patients, which investigators purport reflects the need for greater education on optimal testing and diagnosis for alpha-1 antitrypsin deficiency (AATD).

“We found that phenotyping of patients with serum A1AT 57 - 99 mg/dL seen at our institution was performed in less than half of the cases. We propose that regular continuous medical educational programs about A1AT phenotyping targeting healthcare providers are warranted,” wrote investigators.

A hereditary disorder defined by attenuated levels of A1AT, AATD can predispose an individual to several comorbidities and often manifests as chronic obstructive pulmonary disease, liver disease, or panniculitis. According to the National Organization for Rare Diseases, approximately 100,000 Americans are believed to have AATD, but estimates indicate 10% or fewer of these individuals with severe deficiency of A1AT have been diagnosed. Aside from being considered a rare disease, many point to the 2-step laboratory testing required to determine A1AT level and phenotyping as a barrier to diagnosis.

Led by Zane Elfessi, PharmD, and colleagues from the University of Chicago and the Jesse Brown Veterans Affairs Medical Center, the current study sought to examine whether testing guidelines are effectuated in clinical practice. With this in mind, investigators designed their study as a retrospective analysis of data obtained from the medical records of patients receiving care at the Jesse Brown Veterans Affairs Medical Center from January 2019 to October 2022. For inclusion in the analysis, patients needed to have a serum A1AT between 57 and 99 mg/dL and, for each case, investigators extracted pertinent demographic, clinical, and pulmonary function tests data from EMR data.

Overall, 30 patients were identified for inclusion in the study. This cohort was 90% male and had a mean age of 60 (Standard Deviation [SD], 18) years. Investigators pointed out 14 participants were African American, 4 were Hispanic, and 12 were non-Hispanic White.

Further analysis of background information revealed 17 of the 30 were either current or former smokers. Investigators also pointed out 14 patients had lung disease, 14 liver disease, and 1 had concomitant lung and liver diseases.

Of the 30 patients identified for inclusion based on serum levels, just 13 underwent phenotype testing. This group of 13 included 7 African American, 1 Hispanic, and 5 non-Hispanic White patients. Results of phenotype testing revealed 6 had MX phenotype, 4 had MS phenotype, and 3 had SZ phenotype. Investigators noted 1 patient died from acute respiratory failure during the study period.

Investigators called attention to multiple limitations in their study. These limitations included the retrospective nature of the study design, being conducted at a single center, and the patient population being predominantly African American males. Despite these limitations, investigators purport the results of their study support a larger, prospective, multicenter study on the topic.

“The reason(s) underlying these phenomena was not addressed in this study. We postulate that it may be related, in part, to the unfamiliarity of practitioners with current A1AT testing guidelines. Whether similar observations are reported by other institutions is uncertain,” investigators added. “To the best of our knowledge, however, no previous studies have reported inadequate A1AT phenotyping in predominantly African Americans and Hispanic patients with serum A1AT 57 - 99 mg/dL. Taken together, we propose that regular continuous medical educational programs about A1AT phenotyping targeting practitioners are warranted.”


  1. Elfessi ZZ, Thomas N, Wong M, Rubinstein I. Alpha-1 Antitrypsin Phenotyping: An Unmet Educational Need of Healthcare Providers. J Clin Med Res. 2024;16(2-3):124-127. doi:10.14740/jocmr5111
  2. NORD. Alpha-1 antitrypsin deficiency - symptoms, causes, treatment: Nord. National Organization for Rare Disorders. March 22, 2024. Accessed May 10, 2024. https://rarediseases.org/rare-diseases/alpha-1-antitrypsin-deficiency/#complete-report.
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