Alpha-1 antitrypsin deficiency is relatively common, very much under recognized, and carries consequences for health risk. Alpha-1 Antitrypsin Deficiency (AATD)

Dr. James K. Stoller

Pulmonary/Critical Care Physician
Chairman, Education Institute at Cleveland Clinic

Alpha-1 Antitrypsin Deficiency (AATD)

“It’s important to know that alpha-1 antitrypsin deficiency is relatively common, very much under recognized and carries consequences for health risk, particularly risk for emphysema, liver disease and in some skin disease, panniculitis.

We know from studies that we and others have done, that individuals with alpha-1 antitrypsin deficiency, will go many years between their first symptom, usually shortness of breath, and the first detection of alpha-1 antitrypsin by a healthcare provider.

Patients with chronic obstructive pulmonary disease should be tested for alpha-1 antitrypsin deficiency with a serum level and a genotype.

There are more than 150 different genetic variants of alpha-1 antitrypsin deficiency. The M-type is normal and the Z-type is the most common severe deficient variant, there are other deficient variants in particular one called the S allele.

Having two copies of the abnormal gene, the ZZ-type, clearly poses a risk for both emphysema and liver disease.

Individuals who have the ZZ-type should be monitored every 6 to 12 months with lung function tests and perhaps every year with liver function tests and perhaps additional testing if they have demonstrated liver disease.

The combination of the S and Z allele together is called the PI*SZ type. In those individuals who are PI*SZ who smoke, they are clearly at higher risk for emphysema than if they didn’t have the PI*SZ type alpha-1 antitrypsin. In individuals who are SZ, it’s important to recognize that about 10% of those individuals will have serum levels that are low enough to pose risk, particularly among smokers. We think of PI*SZ individuals who have low serum levels as being a comparable risk for lung disease as PI*ZZ individuals.

Having one copy of the abnormal gene, the MZ type, poses risk for emphysema in smokers and some probably increased risk of liver disease.

For individuals who carry the MZ type, we certainly need to counsel those patients, encouraging smoking cessation or smoking avoidance, and potentially monitoring for liver function.

What are the treatments for patients who have chronic obstructive pulmonary disease due to alpha-1 antitrypsin deficiency? We, of course, treat these individuals with all the usual therapies for individuals with COPD.

You may wish to consider referral to a pulmonologist, a hepatologist, a gastrologist, or dermatologist, who’s knowledgeable about alpha- 1 antitrypsin deficiency, because there are specific therapies that go beyond our usual treatment of COPD. In alpha-1 antitrypsin deficiency, the currently available specific therapy is called augmentation therapy, which is the intravenous infusion of purified alpha-1 antitrypsin given to individuals with severe deficiency of alpha-1 antitrypsin.

Guidelines suggest that when an individual is found to have severe deficiency of alpha-1 antitrypsin, particularly the PI*ZZ type, that every first-degree relative should be tested. That means siblings, children, and depending on the patient and the circumstances, parents as well.

I think we all recognize that an activated patient is an incredibly important asset and so when patients are informed about their risks, bring results that may suggest risk, I think it’s incumbent upon us to actually address those patients’ concerns. The more we collectively know about this, the better off we’ll be.”

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Sample report: Variant detected, 2 copies (PI*Z)
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