Alpha1 antitrypsin deficiency is a genetic defect on chromosome 14 that causes the liver either not to produce the protein called alpha1 antitrypsin (AAT) or to produce this substance with errors in the structure of its molecules.  These badly formed molecules fold incorrectly and become, by and large, 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 newborn 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 alpha1 antitrypsin deficiency have liver involvement, that figure drops to 2 to 5% with increasing age. However, there are Alpha1 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. Alpha1 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 alpha1 antitrypsin in the form of weekly infusions (augmentation therapy). 

In rare cases alpha1 antitrypsin deficiency also damages other organs such as the skin (panniculitis or the inflammation of subcutaneous fatty tissue), the pancreas and blood vessels (vasculitis).