Lung and Liver Problems with Alpha-1 Antitrypsin Deficiency

November 12, 2012

Lung and Liver Problems with Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is caused by a mutation on chromosome 14 involving the alpha-1 antitrypsin gene. This gene is expressed in the liver and produces the enzyme alpha-1 antitrypsin which blocks another enzyme known as neutrophil elastase which is made by white blood cells in response to a lung infection. The neutrophil elastase enzyme breaks down damaged tissue in the lungs and under normal conditions the alpha-1 antitrypsin can stop this action and prevent it from going to far. Given that the antitrypsin is abnormal it folds into an unusual conformation and gets stuck in the liver. Normally it would pass out of the liver, enter the blood stream and travel to lung tissue. But, it can’t get out. Not only can’t it get out, as it accumulates it does damage to the liver. Without the protection of antitrypsin, the lungs are left open to attack by white blood cells that produce elastase.

This genetic mutation for antitrypsin is called an autosomal recessive disorder. What that means is a person has to inherit a bad gene from mom and 1 bad gene from dad to express the disease. If a person inherits only 1 bad gene from 1 parent they do not express the bad gene however, they become carriers of the bad gene and can pass that off to their offspring. Nevertheless, an alpha-1 antitrypsin deficiency can be serious.

Alpha-1 antitrypsin deficiency eventually does damage to the aveoli in the lungs. Alveoli are small air sacs where gas exchange occurs and the elastase enzyme cleaves proteins in the sacs that are important for expansion and contraction. So, the alveoli cease to function. An individual with this problem will have difficulty in breathing such as shortness of breath, coughing and wheezing. As time passes, infection may set in generating emphysema, asthma or bronchitis along with liver damage such as cirrhosis. In rare cases, patients have developed painful lumps under the skin. The lumps are known as panniculitis.

An alpha-1 antitrypsin deficiency can be very difficult to diagnose simply because it looks like so many other lung disease so quite often it is misdiagnosed. However, once it is suspected a simple blood test can check for antitrypsin levels. Other tests may be required as well.

Fortunately, there is a treatment available for alpha-1 antitrypsin deficiency. This requires a weekly trip to the doctor to get an injection of antitrypsin from a healthy blood donor. Of course, this is not a cure but it will slow down the progression of the disease. Current research is seeking for an answer for this problem and have suggested gene therapy. This is a situation where a good antitrypsin gene is spliced into a modified virus and then the virus is allowed to infiltrate the patients cells. There the virus takes up residence and begins producing antitrypsin restoring the patient back to normal function. Breathing symptoms are treated with typical asthma medications but if the liver and/or lungs are badly damaged the patient may require an organ transplant.


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