Alpha-1-antitrypsin deficit
"Currently, gene therapy clinical trials are being conducted that attempt to correct the genetic defect responsible for AAT deficiency by introducing the correct gene into liver cells, but the results are not yet known".
DR. ARANTZA CAMPO EZQUIBELA
SPECIALIST. PNEUMOLOGY DEPARTMENT
What is alpha-1-antitrypsin deficiency?
Alpha-1-antitrypsin deficiency is a genetic disease characterised by low levels of a substance called Alpha-1-antitrypsin (AAT), which is essential to balance/counterbalance the activity of proteases.
AAT deficiency occurs in 1/2,500 individuals in Europe and is most common in Scandinavian countries. It is due to mutations in the SERPINA1 gene which is transmitted in an autosomal recessive manner. The allele most frequently associated with liver and lung disease is PiZ. Liver and lung disease are independent and have different pathogenic mechanisms.
As a result of the genetic defect, a non-functioning altered form of AAT is produced, which accumulates in the liver, leading to progressive destruction of liver cells until cirrhosis of the liver can develop.
In the lung, AAT deficiency leads to uncontrolled activity of other proteins that are activated during inflammatory states in response to various types of damage (infections, irritants such as tobacco smoke). This leads to progressive destruction of the walls of the alveoli (small sacs located at the end of the airways) which in the long term causes pulmonary emphysema.
The disease occurs in childhood mainly in the liver, although it is more common in adults, and lung disease occurs only in adults as emphysema, being more frequent and earlier in smokers. Liver involvement can manifest as neonatal cholestasis or acute haemorrhagic disease in infants, chronic hepatitis and cirrhosis and portal hypertension in children and adults.
In adults, it is associated with hepatocellular carcinoma and increased susceptibility to liver damage due to alcohol consumption or obesity. Most children with the PiZZ phenotype are asymptomatic, but 10-15% develop liver disease and, of these, a proportion will require liver transplantation in the paediatric age.
Symptoms of alpha-1-antitrypsin deficiency
The symptoms of AAT deficiency depend on the type of inherited genetic defect. The most common symptoms are: Dyspnoea, cough, breath sounds and liver failure.
Dyspnoea (shortness of breath) is usually the first symptom and appears between 30 and 45 years of age.
Dyspnoea may be accompanied by asthma-like coughing and wheezing and increased susceptibility to respiratory infections.
Signs of liver involvement at various levels up to cirrhosis may also be present at diagnosis.
Do you have any of these symptoms?
If you suspect that you have any of the above symptoms,
you should consult a medical specialist for a diagnosis.
How is alpha-1-antitrypsin deficiency diagnosed?
Alpha-1-antitrypsin (AAT) deficiency is typically diagnosed by low levels of AAT in the blood. In patients with a high suspicion of AAT deficiency and borderline AAT levels, it is possible to study peripheral blood AAT variants (phenotypes), which have a different degree of association with the disease.
Radiological examinations such as chest X-ray and lung CT can detect the presence of pulmonary emphysema of varying severity. Respiratory function tests are useful to assess the degree of respiratory dysfunction. Liver involvement and the presence of complications can be studied with blood tests, ultrasound, CT and/or MRI of the liver.
How is alpha-1-antitrypsin deficiency treated?
Patients diagnosed with AAT deficiency should minimise exposure to infectious agents and respiratory tract irritants (smoking cessation, vaccination against influenza and the main agents responsible for pneumonia).
The use of bronchodilators and oxygen therapy is indicated when there is airflow obstruction or hypoxaemia (low blood oxygen levels). Intravenous administration of TAAs has been possible for some years and may be useful in adult patients with documented pulmonary involvement by respiratory function tests.
While TAA treatment can improve respiratory function in patients with compromised respiratory function, this treatment has no effect on liver disease and the only treatment for advanced liver disease is liver transplantation.
Where do we treat it?
IN NAVARRE AND MADRID
The Department of Pneumology
of the Clínica Universidad de Navarra
Specializing in smoking and tobacco-related diseases, the Department has over 15 years of experience in smoking cessation and lung cancer early detection programs.
The department's specialists have received training at leading centers around the world, including centers in the United States, and have extensive experience in the diagnosis and treatment of all respiratory diseases, both common and rare.
Diseases we treat
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Why at the Clínica?
- Leading clinical assistance with great work in research and teaching.
- Specialized nursing team.
- We work together with the Sleep Unit and the Lung Cancer Area.
Our team of alpha-1-antitrypsin deficiency experts
