Have you gotten too many Z's?

Alpha-1 Antitrypsin Deficiency (AAT) is an inherited disorder that can cause lung and liver disease in adults and liver disease in children.

AAT is a protein that is produced in the liver. This protein helps to protect the lungs from developing chronic long-term lung disease. The lack of alpha-1antitrypsin protein leads to progressive lung damage, especially when combined with environmental teratogens and other factors, including smoking.

What on earth does all that have to do with getting too many Z’s you ask?

First there needs to be a basic understanding of allele sequencing.

Example of allele sequencing would be human blood typing “AB”.

One “A” type allele plus one “B” type allele would render a result of Type “AB” blood.

The genomes, or alleles, related to this deficiency are mutations within the SERPINA1 gene. This gene provides a mapping, if you will, for the making of a protein called alpha-1 antitrypsin protein(AATP).

AATP protects the body from infection by behaving as the gatekeeper for another powerful enzyme called neutrophil elastase. Normally neutrophil elastase helps the body fight infection when it is released from the body’s white blood cells. But occasionally it can have an auto-immune effect, whereby it will attack the bodies own normal tissue, such as that of the lungs, if an individual does not have enough or any AATP.

Stay with me now. We’re almost to the “Z” factor and specifically why it is not a good thing to have too many.

The most common (allele) of the SERPINA1 gene is the M allele, also know as PiM (protease inhibitor M).

The M allele produces normal levels of AATP. Most people are born with two sets of the M allele (PiMM), in each cell. One copy from the mother and one copy from the father.

Other variations of the alleles are PiMS, PiMZ, PiSZ, PiSS, and PiZZ.

Tadah! Finally, we’re at the “Z” factor.

The double “Z” (PiZZ) combination is of the most concern as this allele produces the least amount of alpha-1 antitrypsin protein and will most likely develop into AAT deficiency and will therefore lead to tissue destruction, primarily of the lungs.

Statistics show about 100,000 individuals have been identified in the US and 161 million, worldwide( http://www.alphaone.org/alphas/?c=01-What-is-Alpha-1-Alphas) have been identified with some variation of the MS or MZ allele. Carriers of the MS (or SS) alleles are said to have enough alph-1 antitrypsin protein on board to protect the lungs. MZ’s, however, carry a higher risk of developing impaired lung or liver function.

It is further thought that AAT deficiency is an inherited disorder and it is strongly suggested that if someone in the family has been discovered that others in the family should similarly be tested.

Discovery is usually determined by a simple blood test. Symptoms can occur in individuals as young age 20 to 50.

Early Signs:

Shortness of breath with mild activity, asthma that is refractory to treatment or year-round allergies and wheezing. Additional early signs might be a noticed unintentional weight loss, re-occurring respitory infections, such as bronchitis’ and/or pneumonias. Fatigue, rapid heart beat upon standing and vision abnormalities have also been reported.

Late signs: extreme difficulty breathing, hacking cough, use of accessory muscles leading to a barrel chest effect.

Red Flags: persons diagnosed at a young age with diseases normally associated with

long-term chronic lung disease that have never smoked should be tested for this life threatening disorder.

Liver disease in children is an unusual finding and thus is considered highly suspect. The child with a diagnosed liver disease should be tested for AAT.

Treatment specific for individuals living with this disorder are weekly administration of protease inhibitor-human (Prolastin) augmentation therapy infusions. The infusion can be administered in a physician’s office or in the home setting. Should more advanced disease be present, lung and or liver transplantation are other options.

It is extremely important for the clinician to advocate cessation of tobacco use, as smoking greatly increases tissue damage in AAT individuals and negates the effects of augmentation infusion therapy.

In Conclusion

There is no cure for AAT but the outlook for individuals is generally thought to be hopeful, especially with the implementation of Prolastin infusions, nutritional counseling, and smoking cessation treatment plans. Patients are advised to have a yearly flu vaccine and a pneumonia vaccine every 5-6 years to safeguard against pollutants and other infectious process.

Antibiotic prophylaxis has been found to be helpful during acute respitory outbreaks.

To protect the liver, it is advised to have, both, Hepatitis A and B vaccines administered.

Not surprisingly, many individuals do not even know that they have the condition. They have been diagnosed with other lung conditions such as COPD (chronic obstructive pulmonary disease), for one.

Again, it is highly unusual for a person in their twenties to have developed COPD since it is has been categorized as a secondary co-morbid issue related to long-term chronic illness. Progressive lung and liver disease affects only a minority of the population. See the following link for the most recent data http://www.genome.gov/19518992.

If you suspect the possibility that AAT is affecting you or any family member then a few common medical tests may help toward a definitive diagnosis AAT.

1)Blood tests (specific to the discovery of AAT)

2) Pulmonary function testing

3) Chest x-rays

4) CT(computerized tomography) scans are among the testing to be completed.

As always, talk with your physician. Discuss any questions and concerns, if you suspect that yourself, or a family member may be “getting too many Z’s”.

The following is a listing of informative websites about Alpha-1 antitrypsin deficiency :

Follow the links below for related diseases and latest updates.

http://en.wikipedia.org/wiki/Alpha_1-antitrypsin_deficiency.  

www.alpha1.org

AlphaNet.org

LungHelpline.com

Adrianna is a Registered Nurse(RN) in the United States that specializes in caring for individuals suffering the effects of multiple chronic diagnoses of the heart, lung and liver.