Alpha-1-antitrypsin deficiency Flashcards
What is Alpha-1 Antitrypsin Deficiency (AATD)?
AATD is a genetic disorder caused by a deficiency of alpha-1 antitrypsin, leading to increased elastase activity, resulting in lung and liver disease.
What type of emphysema is associated with AATD?
Panacinar (panlobular) emphysema, which affects the lower lobes of the lungs, unlike centrilobular emphysema seen in smokers.
What is the inheritance pattern of AATD?
AATD is an autosomal codominant disorder, meaning individuals inherit one allele from each parent, and both can contribute to disease severity.
What are the common genotypes in AATD?
MM (normal), MZ (mild disease), and ZZ (severe disease). The Z allele is associated with increased risk of disease.
On which chromosome is the AAT gene located?
The AAT gene (SERPINA1) is located on chromosome 14.
What are the main pulmonary features of AATD?
Early-onset COPD (before age 45), panacinar emphysema, dyspnea, wheezing, and increased susceptibility to respiratory infections.
How does AATD cause lung disease?
Deficiency of AAT leads to unchecked neutrophil elastase activity, resulting in the destruction of alveolar walls and development of COPD.
How does AATD cause liver disease?
Misfolded AAT protein accumulates in hepatocytes, leading to liver dysfunction, transaminitis, cirrhosis, and increased risk of hepatocellular carcinoma.
What is panniculitis in AATD?
Panniculitis is an inflammatory condition of the fat layer under the skin, presenting with painful, erythematous nodules. It is a rare complication of AATD.
What is the first diagnostic step for suspected AATD?
Measure serum alpha-1 antitrypsin (AAT) levels.
What is the definitive test for diagnosing AATD?
Genotypic analysis using PCR to detect SERPINA1 mutations.
What histological stain is used to confirm AATD-related liver disease?
Periodic Acid-Schiff (PAS) stain with diastase digestion shows PAS-positive, diastase-resistant inclusions in hepatocytes.
What is the treatment for AATD?
Standard COPD management (bronchodilators, steroids), smoking cessation, avoidance of occupational pollutants, and IV AAT replacement therapy for eligible patients.
What are the main hepatic features of AATD?
Neonatal hepatitis, chronic liver disease, cirrhosis, and hepatocellular carcinoma.
How does smoking affect AATD?
Smoking further reduces AAT levels and accelerates lung destruction, worsening COPD progression.
How does Wegener’s Granulomatosis (Granulomatosis with Polyangiitis - GPA) relate to AATD?
There is an increased prevalence of proteinase 3 (PR3)-ANCA-associated vasculitis in AATD patients, potentially linking AATD to GPA. It is important to know that Granulomatosis with Polyangiitis is c-ANCA positive (not p-ANCA).
Why is IV AAT therapy used in AATD?
IV AAT therapy increases serum AAT levels, preventing further lung damage by reducing elastase activity.
What are the contraindications to IV AAT therapy?
Active smoking (since it worsens disease progression) and non-respiratory AATD phenotypes (e.g., isolated liver disease).
How is AATD different from smoking-induced COPD?
AATD COPD affects the lower lobes (panacinar emphysema), while smoking-induced COPD affects the upper lobes (centrilobular emphysema).
What imaging findings are characteristic of AATD?
Chest CT shows panacinar emphysema, particularly in the lower lobes, and signs of liver cirrhosis in affected individuals.
Why is AATD sometimes misdiagnosed as asthma?
Patients may present with wheezing and dyspnea that initially responds to bronchodilators but worsens over time.
What is the prognosis for AATD patients?
Without treatment, patients may develop early COPD and liver disease, but IV AAT therapy and smoking cessation can improve outcomes.
What is the best preventative measure for AATD patients?
Smoking cessation and avoiding occupational lung irritants to reduce lung disease progression.
What are the indications for lung or liver transplantation in AATD?
Severe end-stage lung disease (FEV1 <25%) or cirrhosis with liver failure.
