Alpha1-Antitrypsin (AAT) Deficiency Clinical Presentation

Updated: Sep 11, 2020
  • Author: Dora E Izaguirre Anariba, MD, MPH; Chief Editor: John J Oppenheimer, MD  more...
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Not all the population with AAT deficiency (AATD) develops attributable disease. [2] The presentation of disease depends on the type of mutation associated with AATD However, most of the symptoms secondary to AATD are limited to the respiratory system. [1] Liver diseases such as cirrhosis and chronic hepatitis are the result of the abnormal accumulation of AAT within the hepatocytes and hepatoma, and emphysema due to loss of the proteolytic protection of the lung are the two major clinical presentations of AATD of the PiZZ type. Less common associations are panniculitis and an increase in the association of cytoplasmic antineutrophil cytoplasmic antibody‒positive vasculitis. [5]

The initial symptoms of alpha1-antitrypsin deficiency include cough, sputum production, and wheezing. Symptoms are initially intermittent, and, if wheezing is the predominant symptom, patients often are told they have asthma. If recurrent episodes of cough are most prominent, patients may be treated with multiple courses of antibiotics and evaluated for sinusitis, postnasal drip, or gastroesophageal reflux.

Dyspnea is the symptom that eventually dominates AATD (84%). [1]

Similar to other forms of emphysema, the dyspnea of AATD is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.

Patients with AATD frequently develop dyspnea 20-30 years earlier (at age 30-45 y) than do smokers with emphysema and normal alpha1-antitrypsin levels.

Cigarette smoking accelerates the progression of emphysema in patients with AATD. Symptoms develop about 10 years earlier in alpha1-antitrypsin-deficient individuals who smoke regularly.

By the time dyspnea becomes the dominant manifestation and a diagnosis is established, most patients will have seen several physicians over several years. Efforts to improve the interval between the onset of symptoms and the diagnosis of AATD have been disappointing. Between 1968 and 2003, a significant improvement has not been noted in the average interval (approximately 8.3 +/- 6.9 y) and the number of medical evaluations before an initial diagnosis is made. [2, 12] It should be noted, however, that improvement has been shown in AATD detection in older individuals. [12]

Based on a large clinical population study, Bornhorst et al suggested that early diagnosis of AATD is sporadic and average age of diagnosis is 45.5 ± 9.5 years, as noted in earlier surveys. [10]

Often this diagnosis is missed, as it presents similarly to other more common illnesses such as asthma, COPD, or chronic cough. Thus, the healthcare provider must have a high level of suspicion and consider AATD in the differential diagnosis.


Physical Examination

No single physical sign confirms a diagnosis of alpha1-antitrypsin deficiency (AATD) emphysema. Signs characteristic of increased respiratory work, airflow obstruction, and hyperinflation eventually develop but are dependent on the severity of emphysema at the time of diagnosis.

Increased respiratory work is evident as tachypnea, scalene and intercostal muscle retraction, and tripod position.

Airflow obstruction manifests as pursed-lip breathing, wheezing, and pulsus paradoxus.

Hyperinflation results in barrel chest, increased percussion note, decreased breath sound intensity (see breath sound assessment video, below), and distant heart sounds.

Breath sound assessment. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.

Patients with mild emphysema generally have no abnormal findings on physical examination. Even moderate disease may be evident only when a complicating acute infection occurs. Most of the signs generally considered a part of emphysema (from any cause) are signs of moderate-to-severe disease. Mild-to-moderate disease is easily missed if the physician relies solely on physical findings.

In those with unexplained liver disease with or without respiratory symptoms should be evaluated for AATD. Assessment for signs for stigmata of chronic liver disease, and panniculitis must be performed. Hepatomegaly can be seen, but is not specific for AATD.



Alpha1-antitrypsin-deficient patients are subject to all the complications characteristic of patients with chronic obstructive pulmonary disease from cigarette smoking. Complications may include pneumothorax, pneumonia, acute exacerbation of airflow obstruction, and respiratory failure.