Alpha 1 Antitrypsin Deficiency

Question 1

Which gene is mutated in alpah1 antitrypsin deficiency and what does it encode for?

Answer 1

SERPINA1
Protease inhibitor called alpha 1 antitrtypsin

Question 2

What chromosome is the gene for alpha 1 antitrypsin found on?

Answer 2

14

Question 3

What types of gene mutation is in alpha 1 antitrypsin deficiency? E.g. Dominant/recessive

Answer 3

Autosomal Co-dominant

Question 4

Where is alpha 1 antitrypsin produced?

Answer 4

Liver

Question 5

Where is elastase secreted from?

Answer 5

Neutrophils

Question 6

What is the function of alpha 1 antitrypsin?

Answer 6

Inhibits the neutrophil elastase’s enzyme .: protects connective tissue

Question 7

What are the 2 main organs affected in alpha 1 antitrypsin deficiency?

Answer 7

Lungs
Liver

Question 8

When can liver cirrhosis occur in alpha 1 antitrypsin deficiency?

Answer 8

Any age

Question 9

What causes liver cirrhosis in alpha 1 antitrypsin deficiency?

Answer 9

Build up of mutant alpha 1 antitrypsin in the hepatocytes cause it liver damage

Question 10

What can cirrhosis from A1AT deficiency lead to?

Answer 10

HCC

Question 11

What do you develop in the lungs if you have A1AT deficiency?

Answer 11

Bronchiectasis
Emphysema

Question 12

When do the lung manifestations of A1AT deficiency occur?

Answer 12

After 30 yo

Question 13

How does A1AT deficiency effect the lungs?

Answer 13

Lack of normal A1AT protein leads to excess elastase attacking the connective tissue in the lungs causing COPD

Question 14

What 2 things is A1AT deficiency less commonly associated with?

Answer 14

• Panniculitis (tender skin nodules caused by inflammation of subcutaneous fat)
• Granulomatosis with polyangitis (a small and medium vessel vasculitis)

Question 15

What are the pulmonary features of A1AT deficiency? (4)

Answer 15

○ Dyspnoea
○ Cough
○ Wheeze
○ Ankle swelling (right-sided heart failure from chronic lung disease)

Question 16

What are the hepatic features of A1AT deficiency? (10)

Answer 16

○ Jaundice
○ Bruising
○ Spider naevi
○ Palmar erythema
○ Hepatomegaly
○ Ascites
○ Leuconychia
○ Confusion
○ Asterixis: flapping tremor (suggests encephalopathy)
○ Cachexia

Question 17

What is the screening test for A1AT deficiency?

Answer 17

Low serum alpha 1 antitrypsin
<0.8

Question 18

What is seen on a liver biopsy in A1AT deficiency? (2)

Answer 18

Cirrhosis
Acid-Schiff-positive staining globules resistant to diastase treatment (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes

Question 19

What is included in the management of A1AT deficiency? (9)

Answer 19

• Stop smoking (smoking dramatically accelerates emphysema)
• Decrease alcohol intake
• Nutritional support
• Pulmonary rehab (if needed)
• Seasonal vaccination (to prevent respiratory infections)
• Symptomatic management
• NICE recommend against the use of replacement alpha-1-antitrypsin, however the research and debate is ongoing regarding the possible benefits
• Organ transplant for end-stage liver or lung disease
Monitoring for complications (e.g. hepatocellular carcinoma)