To determine the factors most likely to predict the laboratory diagnosis of Alpha-1-Antitrypsin Deficiency (AATD).
The University of Florida AATD Detection Database was used to evaluate individuals >16 y/o (n=25,090) who were genotyped for the S and Z alleles from 8/2003–3/2008. Each dried blood sample had a brief medical history questionnaire. We grouped the questions into to 5 categories (A-E), A-respiratory diseases, B-liver disease, C-respiratory and liver diseases, D-Family history of respiratory disease (including AATD), E-family history of respiratory disease and the presence of respiratory and/or liver diseases.
Of the total number of questionnaires, 30.5% did not report any medical history. The remaining questionnaires fell into the following groups: A (54%), B (4.7%), C (3.2%), D (3.2%), E(4.3%). A total of 288 individuals (1.1%) were determined to be PI ZZ and 2,039 pts (8.1%) had at least one Z allele. Group A (respiratory disease) and B (liver) had no predictive value. The odds ratios for having Pi*ZZ genotype were significantly increased for group C- 2.26 (95%CI 1.3–3.8), group D- 6.8 (95%CI 4.9–9.6) and group E- 5 (95%CI 3.5–6.9). Similarly, the odds ratios for having at least one Z allele were for group C- 2.26 (95%CI 1.3–3.8), D- 6.8 (95%CI 4.9–9.6) and E- 4.95 (95%CI 3.5–6.9).
While respiratory diseases (predominantly emphysema) was the most common reported medical history, a family history of respiratory and/or the combination of respiratory and liver diseases were associated with the highest odds ratios for the determination of Z allele in either the homozygous or heterozygous combination.
The presence of a family history of respiratory diseases is highly predictive for the presence Alpha-1-Antitrypsin Deficiency and should prompt a physician to test for alpha-1-antitrypsin deficiency.
Adriano Tonelli, Grant monies (from sources other than industry) Alpha-1-Foundation; Grant monies (from industry related sources) Talecris Biotherapeutics Inc.; No Product/Research Disclosure Information