Diseases

Hereditary Pulmonary Emphysema (Alpha 1 Antitrypsin Deficiency) Information

Alpha-1 antitrypsin deficiency definition and facts*

*Facts medically reviewed by Charles P. Patrick, MD, PhD

• Alpha1 antitrypsin deficiency (AATD, antitrypsin deficiency, or alpha 1 antitrypsin deficiency) is a disorder (disease) that causes the alpha-1 antitrypsin (AAT) protein to be reduced or missing from the blood. This protein is necessary for healthy lungs, and the body uses it to protect the lungs from damage. If a person has low or no levels of AAT their lungs may be damaged.
• Statistically, the disorder affects about one in 1500 to 3500 individuals with European ancestry. It is uncommon in Asians.
• The signs and symptoms most people experience with this deficiency are:
  • Chronic cough
  • Emphysema
  • COPD
  • Liver failure
  • Hepatitis
  • Hepatomegaly (enlarged liver)
  • Jaundice
  • Cirrhosis
• Mutations in the gene termed SERPNA1 cause alpha –1 antitrypsin deficiency.
• A patient with lung or liver disease like COPD (chronic obstructive pulmonary disease) with no obvious cause maybe AATD deficient.
• Doctors can confirm the diagnosis of this deficiency with blood tests or liver biopsy.
• How doctors treat AATD depends on the patient’s signs and symptoms. Examples of treatments include:
• Bronchodilators and inhaled steroids can help lung problems.
• Intravenous use of purified human ATT (Prolastin) raise the level of ATT in the blood and lungs (augmentation therapy) - end stage lung and liver disease may need transplantation of these organs as a definitive treatment.
• Management of AATD involves pulmonary function tests, liver function monitoring and yearly vaccinations against influenza. Moreover, doctors recommend that patient’s with the deficiency be vaccinated against hepatitis A and B, and pneumococcus.
  • Stop smoking or reduce exposure to secondhand smoke.
  • Reduce exposure to environmental pollutants.
• The prognosis for someone with this problem is quite variable, and is related to the development and progression of severity of the symptoms. However, many people have a somewhat shortened lifespan. If the symptoms are severe, the prognosis can be very poor.
• Medical professionals refer to alpha-1 antitrypsin deficiency.
  • AAT
  • AATD
  • Alpha-1 proteinase inhibitor
  • Alpha-1 related emphysema
  • Genetic emphysema
  • Hereditary pulmonary emphysema
  • Inherited emphysema

Alpha-1 antitrypsin deficiency treatment and management guidelines

Treatment of alpha-1 antitrypsin deficiency (AATD) depends on the symptoms and severity in each person. COPD and other related lung diseases are typically treated with standard therapy.[3][4] Bronchodilators and inhaled steroids can help open the airways and make breathing easier.[4]Intravenous augmentation therapy (regular infusion of purified, human AAT to increase AAT concentrations) has been recommended for people with established fixed airflow obstruction (determined by a specific lung function test).[3] This therapy raises the level of the AAT protein in the blood and lungs.[4]Lung transplantation may be an appropriate option for people with end-stage lung disease. Liver transplantation is the definitive treatment for advanced liver disease.[3]When present, panniculitis may resolve on its own or after dapsone or doxycycline therapy. When this therapy does not help, it has responded to intravenous augmentation therapy in higher than usual doses.[3]All people with severe AATD should have pulmonary function tests every 6 to 12 months. Those with ATT serum concentrations 10% to 20% of normal should have periodic evaluation of liver function to detect liver disease. People with established liver disease should have periodic ultrasounds of the liver to monitor for fibrotic changes and liver cancer (hepatocellular carcinoma).[3]Yearly vaccinations against influenza and pneumococcus are recommended to lessen the progression of lung disease. Vaccination against hepatitis A and B is recommended to lessen the risk of liver disease. People with AATD should avoid smoking and occupations with exposure to environmental pollutants.[3]Parents, older and younger siblings, and children of a person with severe AATD should be evaluated to identify as early as possible those who would benefit from treatment and preventive measures.[3]Management guidelines

• GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
• Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition

Chart of signs and symptoms of lung and liver disease caused by AATD

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies.Signs and Symptoms of Alpha-1 Antitrypsin DeficiencySigns and SymptomsApproximate number of patients (when available)EmphysemaVery frequent (present in 80%-90% of cases)Hepatic failure (liver failure)Very frequent (present in 80%-90% of cases)Hepatitis (liver inflammation or infection)Frequent (present in 30%-79% of cases)An abnormally enlarged liver (hepatomegaly)Frequent (present in 30%-79% of cases)Jaundice (signs of a liver problem)Frequent (present in 30%-79% of cases)Cirrhosis (a complication of liver disease)Occasional (present in 5%-29% of cases)Autosomal recessive inheritanceCOPD (chronic obstructive pulmonary disease)Shortness of breath (Dyspnea)Elevated hepatic transaminasesLiver cancer (hepatocellular carcinoma)

FDA approved treatment medications for AATD

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.Alpha1-Proteinase Inhibitor (Human) (Brand name: Prolastin) - Manufactured by Grifols United States: FDA-approved indication: For chronic replacement therapy of individuals having congenital deficiency of alpha1- proteinase inhibitor with clinically demonstrable panacinar emphysema.