Alpha-1 antitrypsin deficiency: Am I at risk?

Humans possess every piece of genetic information in duplicate; each gene comes once from the mother and once from the father. This is also true for the gene that carries the "blueprint" for the protective protein alpha-1-antitrypsin. Various variations are known, which affect alpha-1-antitrypsin levels in the blood to varying degrees:

The M variant This is the conventional, "healthy" variant. In this case, a normal alpha-1 antitrypsin level is produced with normal function. The M variant is found in most people.
At the Z-variant This leads to clumping of the protective protein in the liver cells, preventing its release into the bloodstream. The result is a reduction in the alpha-1 antitrypsin level in the blood. Carriers of this variant are found primarily in Northern Europe and the Middle East.
In southern Europe, this occurs more frequently. S variant, in which there is usually a slightly higher concentration of alpha-1 antitrypsin in the blood than in the Z variant.
In the case of the very rare occurrence Zero variant No protective protein is produced at all. This leads to an extremely high risk for the lungs, whereas the liver is not affected by this gene variant.
Our scientific advisor, Dr. Timm Greulich, describes further very rare variants.

The effects of alpha-1 antitrypsin deficiency on the lungs usually only become apparent when both blueprints of the protective protein have certain deviations, i.e., when one has inherited a defective gene variant from each parent.

The situation may be different with regard to the effects on the liver, as it has recently become apparent that carriers of both variants M and Z (PiMZ) may also have an increased predisposition for liver changes.

M = healthy gene

Z = altered gene

1M+1Z = heterozygous, two different variants of the AAT gene

2Z = homozygous, two identical AAT genes

2M = homozygous, two identical AAT genes

Who should get tested for alpha-1 antitrypsin deficiency?

People with relatives who have already been diagnosed with alpha-1 antitrypsin deficiency (family screening).
Anyone suffering from chronic obstructive pulmonary disease (COPD) should also be tested for alpha-1 antitrypsin deficiency once in their lifetime to rule out that the symptoms are due to the genetic defect.
People with elevated liver enzyme levels.
People with frequent inflammation of the bronchi and/or pneumonia and/or other lung diseases, especially if these occur at a young age.

Alpha-1 patients can be hidden among the following patient groups due to similar symptoms:

COPD patients: In people with chronic obstructive pulmonary disease (COPD), exhalation is particularly difficult. COPD is also known as "smokers' disease"—although there are other risk factors for COPD (e.g., exposure to dust).
Asthmatics: The respiratory disease "bronchial asthma" can also show symptoms similar to alpha-1 antitrypsin deficiency.
Panniculitis: This refers to inflammation of the subcutaneous fat tissue. An alpha-1 antitrypsin deficiency can also be the underlying cause of such a condition.
Liver disease patients: In alpha-1 antitrypsin deficiency, the liver can be affected in addition to the lungs, leading to hepatitis and, in the worst case, cirrhosis. Liver involvement often manifests in childhood.

Grafik: Risikogruppen Alpha-1-Antitrypsinmangel

Why should COPD patients in particular get tested for Alpha-1?

COPD, commonly known as "smoker's disease," exhibits the same symptoms as alpha-1 antitrypsin deficiency: shortness of breath, chronic cough, and increased sputum production. However, because COPD is more widely known and prevalent, there is a risk that many people with alpha-1 deficiency will not be correctly diagnosed: they are prematurely labeled as COPD patients – and consequently, not treated specifically and therefore not optimally.

By the way:

On average it takes 7 years, until an Alpha learns the true cause behind his symptoms.
Until then, he usually 5 doctors sought out because of his associated health problems.

This shows that alpha-1 antitrypsin deficiency is still too little known – to the detriment of (undiagnosed) patients. The disease can be caused by a simple test to be proven or disproven.