What Is Alpha-1 Antitrypsin Deficiency?

By John Bottrell, RRT

3 min read

There is a rare form of genetic COPD. It’s the only subtype of COPD known to be hereditary. It’s caused because you have a mutated gene. The gene that is mutated is the alpha-1 antitrypsin gene. When you have this, you may develop a rare form of COPD. It’s called alpha-1 antitrypsin deficiency. It’s often called genetic COPD. Other names for it may be α1 antitrypsin or simply α1. Here’s all you need to know.

What causes alpha-1 antitrypsin deficiency?

It’s rare. It affects fewer than 5% of people with COPD.¹ If you have this gene mutation, you may get COPD even if you never smoked or were never exposed to other noxious substances in the air. And, it’s one of the few known things that may cause a diagnosis of COPD before the age of 40.

The gene affected is the SERPINA1 gene. It’s on chromosome 14. This gene encodes (makes) a protein called alpha-1 anti-trypsin. It’s made by the SERPINA1 gene. But, it’s secreted by the liver. What it does is travel through the bloodstream. It goes into liver tissues. There, it serves the noble job of helping to keep the lungs healthy and working properly.^1-2

It works by eating or destroying a protein called Neutrophil Elastase. Like alpha-1 antitrypsin, neutrophil elastase is a blood protein. It’s made by the ELANE gene. Its job is to eat up or destroy dead and decaying lung cells. It does this so newer lung tissue can grow in its place. This is how the lungs stay fresh and healthy.^{1, 3-4}

This is a noble job. However, with every gene that releases something that does a job, there is another gene that does the opposite. And this is where the alpha-1 antitrypsin comes in handy. Alpha-1 antitrypsin is secreted by the liver. It travels through the blood to lung tissue. There, it prevents neutrophil elastase levels from getting too high.

This is very important. Because neutrophil elastase is a protein that gets bored easy. When it runs out of dead and decaying lung tissues to destroy, it starts to destroy healthy lung tissue. When this happens, it can eventually cause a diagnosis of emphysema.

What is alpha-1 antitrypsin deficiency?

It’s caused by a mutation on the SERPINA1 gene. No one knows why nor when these mutations occurred. But, it is estimated that there are over 100 varieties of this gene. And, of course, it’s not your fault you got it if you have it. It’s something that is handed down from one generation to the next.¹

So, there are many alpha-1 genes. These are referred to as genotypes. We may refer to these as subtypes or subgroups or simply types or even variety. The most common genotype is indicated by an M. Most people will get one M gene from each parent, indicated as MM genotype. These people will have healthy alpha-1 antitrypsin levels. They will not develop genetic COPD.^{1, 4}

The two genotypes most known for causing alpha-1 antitrypsin deficiency are indicated as S and Z. Some people may get an S and a Z from each parent (SZ genotype). Sometimes this may cause a person to develop alpha-1 deficiency. However, the most likely combination to cause this rare condition is those who receive a Z from each parent (ZZ genotype).^1,4

The ZZ genotype causes low levels of alpha-1 to be secreted by the liver. This causes an abnormal alpha-1 antitrypsin to remain in the liver. This is what causes liver disease. Low levels of blood alpha-1 antitrypsin levels are what causes emphysema. The other alpha-1 genotypes may cause different effects on the lungs and kidneys and may cause no symptoms at all.¹

At the present time, there are about 100,000 people diagnosed with alpha-1 ZZ. This is less than 5% of all the people living with COPD worldwide. However, despite it affecting up to 5% of the COPD community, it is estimated that only about 5% have a proper diagnosis. So, this is why awareness of this rare form of COPD is so important. It simply isn’t being diagnosed enough. And this should explain all the articles on this subject in this community.^1,4

Testing for this is a simple blood test. The test can determine if you have low levels of alpha-1 antitrypsin in your blood. It can also determine what genotype you have. And getting that proper diagnosis can lead to more treatment options. This is all in our quest to help people living with COPD breathe easier and live better and longer despite their diagnosis.

In an upcoming post, I will describe the test in more detail, along with how other ways of getting to a proper diagnosis of alpha-1 antitrypsin deficiency. So, stay tuned!!!

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The COPD.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

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bayoumama Member
How can I get tested for alpha-1 deficiency?
1. John Bottrell, RRT Moderator & Contributor
 <inline-mention username="bayoumama" user-id="6885727"/> Great question. The best way to get tested is to talk to your doctor. There is a simple blood test that your doctor can order. Is this something you are considering doing? John. <a href='https://copd.net' target='_blank'>copd.net</a> community moderator.
Tervlvr Member
I have Alpha-1 and an SZ. It took several years before I was tested for it. I am 99.99% sure my mother had it. She was almost 88 when she passed and was on 16 liters of O2. Thank you for all the good information provided here.
MikeD Member
I am actively chasing this as a possible diagnosis. It's important to note that a simple blood test (serum levels) can't rule out Alpha1. There are extra rare variants that produce normal serum levels but the proportions don't function. And augmentation therapy might be available!
1. MikeD Member
 Unfortunately, I am back to "Your lungs are not great" as a diagnosis. (43years-old, no smoking history, family history of idiopathic severe lung conditions)
2. Leon Lebowitz, RRT Member
 Hi again, <inline-mention username="MikeD" user-id="6642078"/> - I hear you! I did have an opportunity to review your conversations (here on COPD.net).and so, I have a good idea of your present medical condition based on what you've shared with the community in the past. It must be somewhat disappointing to have been told "your lungs are not great" - I hear you and I understand that! Every patient deserves to have an honest and direct presentation of their specific medical condition. Since your family has a history of idiopathic severe lung conditions and, you have said that you have a COPD diagnosis (at 40%), I would suggest you have a serious conversation with your private medical doctor. I would hope that a conversation like this will provide you with more details about your pulmonary health status as well as current and future treatment options. I also thought you might find it helpful to look over both your post, as well as the replies from both me and my colleague <inline-mention username="Melissa.Arnold" user-id="4698523"/>, in this conversation (from February 2023): https://copd.net/forums/copd-since-12-years#reply-150058. In it you shared that you had a COPD diagnosis and both Melissa and I were able to provide you with support there. What do you think? Leon L (author/moderator)