Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.
The incidence of alpha-1 antitrypsin deficiency (AATD) worldwide is 1 in every 1500 to 3500 individuals with European ancestry.1 Along with Down syndrome and cystic fibrosis, AATD is one of the three most common, potentially lethal, rare diseases affecting those of European descent.2
In the US, AATD affects 1 in every 3000 to 5000 people. Severe cases of AATD are estimated to affect 70,000 to 100,000 individuals in the US; however, AATD is underdiagnosed or misdiagnosed.3 It is projected that less than 10% of these individuals have obtained an accurate diagnosis.4 Many individuals presenting with symptoms of AATD are diagnosed with asthma or chronic obstructive pulmonary disease (COPD), but they are not tested for AATD with reports of long delays (mean of 5-8 years) to reach an exact diagnosis if it is made at all.5
The prevalence of AATD varies by population.1 It has been observed that confined or isolated populations with less genetic diversity, such as those located in alpine valleys or on islands, seem to have a higher prevalence of the Z and S gene AATD phenotypes.6
AATD has been identified in all racial groups, but it is most prevalent in people with Northern European (1 in 1600) and Spanish or Portuguese descent.3 The Z gene is more frequently found in individuals with Northern or Western European descent, and the mutation for the Z variant is suspected to have arisen in southern Scandinavia.7 The S gene is more common in individuals of Iberian descent, and the mutation most likely occurred in this region.4,7 AATD is relatively uncommon in individuals of Asian descent.1 Overall, AATD affects an estimated 117 million carriers and develops in 3.4 million individuals around the world.3
AATD can present in neonates who have unremitting jaundice at birth. As AATD progresses with more hepatocytes accumulating the abnormally shaped alpha-1 antitrypsin proteins, it can be attributed to cholestatic jaundice in infants, and liver failure or cirrhosis in children.
Onset of lung disease symptoms, especially dyspnea after mild exertion, first start appearing in those with AATD as early as 20 years of age to as late as 50.8 It may take years for an accurate diagnosis to be obtained because AATD shares many similar characteristics with other obstructive lung diseases.4
Among non-smoking adults, AATD is usually officially diagnosed around the fifth decade of life. Smoking exacerbates and accelerates the disease, so AATD is identified in smokers around the fourth decade of life.
AATD affects men and women equally.3 It is not a sex-linked heritable condition.
Prevalence of Comorbidities with AATD
With an estimated number of 175 million cases internationally, COPD ranks 38th on the World Health Organization’s global prevalence for disease. AATD contributes to 1% of these COPD cases.9
A study conducting in Germany using a large healthcare database to obtain information showed that the prevalence of COPD with AATD was 32% and emphysema with AATD was 21%.10 AATD accounts for 2% to 3% of all emphysema cases.5
Researchers in Italy studied the prevalence of bronchiectasis with AATD. In the 475 Italian patients diagnosed with AATD, 12% had the comorbidity of bronchiectasis, detected via high-resolution CT scans of the chest.11
Prevalence of AATD Types
A multicenter prospective cross-sectional study of 3254 patients with a diagnosis of COPD revealed that 1.29% of this population had AATD, 0.92% (95% CI 0.62-1.31) had the Pi*ZZ genotype, and 0.37% (95% CI 0.19-0.64) had the Pi*SZ genotype.12
Recent genetic prevalence indicates that the PI*SZ genotype might be 10 times more prevalent than those with the classic Pi*ZZ genotype. Less frequent diagnosis in clinic accompanied by typically less severe disease characteristics in the Pi*SZ genotype compared with the Pi*ZZ genotype may contribute to this estimation.13 The Z allele is present in 98% of cases with severe disease presentation.14
- Alpha-1 antitrypsin deficiency: frequency. Medline Plus. Accessed on June 2, 2021.
- Anariba, DEI. Alpha1- antitrypsin deficiency: etiology. 2020. Medscape. Accessed on June 1, 2021.
- Anariba, DEI. Alpha1- antitrypsin deficiency: epidemiology. 2011. Medscape. Accessed on June 2, 2021.
- Stoller JK, Brantly M. The challenge of detecting alpha1- antitrypsin deficiency. COPD. 2013;10 Suppl 1:26-34. doi:10.3109/15412555.2013.763782
- Alpha-1 antitrypsin deficiency: affected populations. National Organization for Rare Disorders (NORD). Accessed on June 1, 2021.
- Stoller JK, Aboussouan LS. A review of a1-antitrypsin deficiency Am J Respir Crit Care Med. 2012; 185(3): 246-259. doi:10.1164/rccm.201108-1428CI
- Hutchison, DC. Alpha 1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z. Respir Med. 1998; 92(3):367-377. doi:10.1016/s0954-6111(98)90278-5
- Alpha-1 antitrypsin deficiency. Eugene. Accessed on June 3, 2021.
- Soriano JB. An epidemiological overview of chronic obstructive pulmonary disease: what can real-life data tell us about disease management? COPD: Journal of Chronic Obstructive Pulmonary Disease. 2017; 14(S1): S3-S7. doi:10.1080/15412555.2017.1286165
- Greulich T, Nell C, Hohmann D, et al. The prevalence of diagnosed α1- antitrypsin deficiency and its comorbidities: results from a large population-based database. European Respiratory Journal. 2017; 49(1). doi:10.1183/13993003.00154-2016
- Cortese R, Mennitti MC, Mariani F, et al. Bronchiectasis in patients with alpha1-antitrypsin deficiency: prevalence and characteristics. European Respiratory Journal. 2016; 48(suppl 60). doi:10.1183/13993003.congress-2016.PA737
- Menga G, Fernandez Acquier M, Echazarreta AL, et al. Prevalence of alpha-1 antitrypsin deficiency in COPD patients in Argentina. The DAAT.AR study. Arch Bronconeumol (Engl Ed). 2020;56(9):571-577. doi:10.1016/j.arbres.2019.11.010
- McElvaney GN, Sandhaus RA, Miravitlles M, et al. Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype. European Respiratory Journal. 2020; 55(6). doi:10.1183/13993003.02410-2019
- Blanco I, Bueno P, Diego I, et al. Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update. Int J Chron Obstruct Pulmon Dis. 2017;12:561-569. doi:10.2147/COPD.S125389
Article reviewed by Michael Sapko, MD, on July 1, 2021.