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November 2018 | Published by RCPA

Issue #086

Alpha-1 antitrypsin deficiency - the facts

Alpha-1 antitrypsin deficiency - the facts

The month of November is alpha-1 antitrypsin deficiency awareness month here in Australia. As this is not a well-known disease in the general community, we spoke to Dr Alan McNeil, a chemical pathologist, to find out more about this inherited disorder, which can cause emphysema and cirrhosis.

“Alpha-1 antitrypsin is a protein that protects the lungs from inflammatory enzymes. These enzymes are there to destroy microbes, but if they are unregulated through the absence of alpha-1 antitrypsin, they damage the fine membranes of the lungs themselves. This is emphysema which causes abnormal expansion of the lungs, progressive breathlessness, and sometimes respiratory failure.

“The disorder is pretty uncommon - it’s an inherited condition that affects approximately 1 in 2000 people in Australia. The particular mutations that are problematic originated in Northern Europe; therefore the condition mainly affects people with European heritage,” said Dr McNeil.

Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency.

“The alpha-1 antitrypsin protein is naturally made in the liver and would normally enter your system to help protect against these enzymes. Some people simply don’t make enough alpha-1 antitrypsin and are at risk of emphysema. However, in those with the most serious mutation, the so-called Z mutation, alpha-1 antitrypsin builds up in the individual’s liver causing chronic liver disease and cirrhosis, as well as emphysema. In simple terms, the condition is caused by this protein, alpha-1 antitrypsin, being stuck in the wrong part of the body and not getting to the parts that it needs to.”

The signs and symptoms of this condition, and the age at which they appear, vary among individuals; however, early symptoms can include shortness of breath following mild activity, reduced ability to exercise and wheezing. Onset of lung problems is typically between 20 and 50 years old.[1]

“In terms of a diagnosis for this disease, if an individual has a family history of alpha-1 antitrypsin deficiency, it’s great to get tested to see if it has been inherited. If not, the disorder may be identified via pathology tests with babies or in adulthood. For those with the Z mutation, the protein accumulates in the liver; therefore this might present in babies with abnormal liver tests or prolonged jaundice. So, for that reason, the first hint can be in babies with liver abnormalities; however, they can often resolve spontaneously, so they may or may not be identified at that stage. If that is missed, some may present later in life with symptoms such as emphysema, shortness of breath, or even respiratory failure. Or it can present in adults with liver problems for the reasons discussed earlier. A patient in their forties, for instance, might have a blood test that shows abnormal liver function, and so they will go through a range of pathology tests to identify the issue.

“The other involvement of the pathologist is when an adult might have a liver biopsy to see why they have abnormal liver function. The pathologist will be able to make the diagnosis by seeing the characteristic accumulation of alpha-1 antitrypsin in the liver.”

“Once alpha-1 antitrypsin deficiency is diagnosed, the treatment needs to be adjusted for the individual patient. Avoiding smoking or air pollution is essential to reduce the risk of progressive emphysema, and reducing alcohol intake for those at risk of liver disease. For people with emphysema and very low alpha-1 antitrypsin levels in their blood, the Therapeutics Goods Administration (TGA) in Australia has approved weekly infusions of alpha-1 antitrypsin. This needs to be organised through your doctor and usually a specialist clinic. This treatment won’t help with the liver disease of course, and some people might eventually require a liver transplant. One advantage of this dramatic treatment is that the new liver will produce the alpha-1 antitrypsin that was not made by the original liver. Genetic testing of family members is also important when someone is diagnosed. One day we hope there will be a treatment where the defective gene is fixed before someone is born,” concluded Dr McNeil.




[1] https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency





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