Alpha-1 antitrypsin deficiency (A1AT) is a genetic defect on chromosome 14 that causes the liver either not to produce the protein called alpha-1 antitrypsin (AAT) or to produce this substance with errors in the structure of its molecules. These badly formed molecules fold incorrectly and are largely unable to leave the liver.
In contrast to the rest of the body, the problem in the liver is not a lack of but rather an accumulation of abnormally folded protein in the liver cells, and this damages them. In turn, the damaged cells can lead to prolonged jaundice in the new-born or bile stasis or chronic liver disease in children. Affected children often have poor appetite and fail to thrive. Although 10 to 20% of children with alpha-1 antitrypsin deficiency have liver involvement, that figure drops to 2 to 5% with increasing age. However, there are Alpha-1 patients who do not develop any symptoms until adult age. They are then more likely to develop cirrhosis (scarring) or cancer of the liver. As yet there is no specific drug treatment for liver alphas.
We inhale and exhale approximately 0.5 litres of air with every breath. This equates to between six and eight litres of air circulated per minute, or around 10,000 litres a day. We also draw exhaust gases, dust, cigarette smoke (actively and passively), pollen, bacteria and much more into our lungs with every breath. The lungs defend themselves against these irritants with a substance (an enzyme) which is secreted by white blood cells and which keeps our lungs clean. Alpha-1 antitrypsin serves to stop this substance from attacking healthy lung tissue. If it is absent or in short supply, this protective function is insufficiently carried out, resulting in damage in the form of pulmonary emphysema, where the tiny air sacs are destroyed. The walls between the air sacs fuse, the lung tissue loses its elasticity and large cavities form and these fill with residual air. Shortness of breath develops – first during physical exertion, but in the advanced stage even at rest. Pulmonary emphysema is irreversible, i.e. the destruction of healthy lung tissue cannot be made good again. This process cannot as yet be halted, but it can be significantly slowed down by supplying alpha-1 antitrypsin in the form of weekly infusions (augmentation therapy).
In rare cases alpha-1 antitrypsin deficiency also damages other organs such as the skin (panniculitis or the inflammation of subcutaneous fatty tissue), the pancreas and blood vessels (vasculitis).
For a more technical explanation, including details of the damage that can occur to the liver, we recommend the following websites.
Additional Information
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Liver
People with the Pi Z gene produce a slightly different form of alpha-1 antitrypsin protein in their liver which becomes trapped and can cause irreversible liver damage. Several different types of liver conditions can be associated with alpha-1 antitrypsin deficiency. These are explained in more detail in our Alpha-1 Antitrypsin Deficiency Information – The Liver (83Kb PDF). If you have a child with liver problems then you may find our Alpha-1 Children page useful. -
Panniculitis
Panniculitis is an inflammation of the fatty tissue layer that lies underneath the outermost or superficial layers of our skin. Sometimes panniculitis is caused by alpha-1 antitrypsin deficiency.Various therapies have been tried and evaluated for the treatment of panniculitis. These include corticosteroids antibiotics (doxycycline and dapsone), full plasma exchange and augmentation therapy. Of these various treatments, augmentation therapy has been the most dramatically successful. Several reports describe resolution of panniculitis after as few as 3 doses of intravenous augmentation therapy. The dose of augmentation therapy for panniculitis is the same as that for established emphysema, 60 mg/kg once weekly.
More details about the condition can be found on the Publications page. If you wish to know more, Contact Us and we will try to help.
