Published in Alpha1 Journal 02/2014

PiMZ is one of the most important topics of the year for us at Alpha 1 Germany. Dr. Steveling from the Ruhrland Clinic in Essen already gave a presentation on this subject at our members' meeting. People with MZ must not be overlooked. This topic is personally important to me, as there are many people with MZ in my family. Therefore, I would like to explain what a diagnosis of heterozygous alpha-1 antitrypsin deficiency (PiMZ) means for each individual.

„"I'm just an MZ and therefore just a carrier," many of those affected who came to the children's day event think. We're talking about affected children, and by that we almost always mean ZZ. Many questions quickly arise: What about the siblings? Were they even tested? Did the parents get tested? Shouldn't we even be thinking a generation further ahead – what about grandparents, aunts, and uncles – were they all tested?

Alpha-1 antitrypsin deficiency is a familial disease

It's easy to forget that we have affected individuals in our families. That was the case in my family, too. When children are affected, the parents also carry a Z allele. It took time to explain to the family that they, too, have a gene mutation. Many affected individuals only perceive themselves as PiMZ carriers. And they might even be bakers, grinders, or smokers. We want to emphasize that this is not a good thing. As Dr. Kardorff explained, even a PiMZ has a slightly higher risk of lung disease (i.e., higher than in MM) because the AAT level in the blood is lower than in the normal variant, PiMM. AAT levels can be high or low within the reference range, but a PiMZ can also have a quite low concentration of AAT in their blood. That's why it's important for PiMZ individuals to know their serum levels.

In Germany, approximately 1,538,000 people with multiple myeloma (MZ) and 12,000 people with multiple myeloma (ZZ) are affected. To illustrate: Statistically, on a bus with 50 people, there is one person with multiple myeloma (PiMZ). The number of people with multiple myeloma (PiMZ) is increasing worldwide. And even if only a few of these individuals develop pulmonary emphysema, this still represents more than the total number of people with multiple myeloma (PiZZ).

The health significance for PiMZ

• A PiMZ should not expect any serious shortages.
• The risk of lung disease is higher than with PiMM
• Smoking has been proven to significantly increase the risk.
• Education is important
• A person with multiple myeloma (PiMZ) often suffers from hypersensitive airways.

We parents must seize the opportunity to influence our children so they don't smoke – neither actively nor passively. In Ireland, it has been observed that smokers with PiMZ (Pilar-Melano-Zenecio) mutations have narrower bronchi and, in the long term, lose more alveoli, thus reducing lung capacity. Fine particulate matter pollution also poses a risk. Occupations such as baker, painter and decorator, chemical laboratory technician, farmer, carpenter, or welder are not recommended. From personal experience within my family, I can speak of hypersensitive airways. This non-specific bronchial hyperreactivity is, however, treatable. Fumes, dusts, and gases that irritate the bronchi should be avoided. Respiratory infections should be prevented through vaccinations (influenza and pneumococcal). Medical treatment for hypersensitive bronchi, for example with inhaled corticosteroids, must be discussed with a doctor. When we talk about possible comorbidities known to us in the PiZZ type, there is no increased risk of other organ diseases in the PiMZ type. Liver cirrhosis, panniculitis, inflammatory bowel diseases, rheumatic conditions, or granulomatosis with polyangiitis (GPA) do not occur more frequently than in people with PiMM.

In summary, it can be said:

• PiMZ (PiZZ anyway) should never smoke or should quit smoking as soon as possible!
• Annual follow-up examinations by a pulmonologist and monitoring of blood values, possibly including determination of serum levels.
• Have nonspecific hypersensitive airways checked and treated by a doctor.
• Genetic counseling also available for PiMZ individuals.

Our recommendation:

Think of yourself too: have your parents, siblings, and of course all your children tested. Watch out for typical symptoms and inform all relatives about this genetically inherited "family disease." In my view, PiMZ is not just about being a carrier!

Published in Alpha1 Journal 02/2014*

*) These findings reflect the state of knowledge at the time of publication of this article (2014). However, in a 2018 study, our scientific advisor Prof. Pavel Strnad and colleagues showed that even among MZ employees a increased risk of liver disease This is the case if other factors such as excessive alcohol consumption, obesity, or diabetes are also present.