alpha 1 antitrypsin deficiency

Question 1

what does this commonly affect

Answer 1

lung (emphysema) and liver (cirrhosis and HCC)

Question 2

what is the deficiency called

Answer 2

serpinopathy as A1AT is in a family of serine protease inhibitors

Question 3

is A1AT deficiency the chief genetic cause of liver disease in children or adults

Answer 3

children

Question 4

what is the deficiency more likely to cause in adults

Answer 4

emphysema.

Question 5

what does lung A1AT protect against

Answer 5

tissue damage from neutrophil elastase (process also induced by cigarette smoking)

Question 6

associations

Answer 6

HCC, asthma, pancreatitis, gallstones, Wegeners

Question 7

what type of inheritance is this and what chromosome is it found on

Answer 7

autosomal recessive, found on chromosome 14

Question 8

what is the normal genotype

Answer 8

PiMM. homozygote is PiZZ and heterozygotes PiMZ and PiSZ

Question 9

what genotype do symptomatic patients have

Answer 9

PiZZ genotype

Question 10

what do patients present with

Answer 10

dyspnoea from emphysema, cirrhosis, cholestatic jaundice.

Question 11

tests

Answer 11

serum alpha 1 antitrypsin levels decrease (<75% of lower limit of normal).

Question 12

why may a low level be hidden

Answer 12

as A1AT part of the acute phase response, inflammation may hide a low level

Question 13

what other tests can be done

Answer 13

liver biopsy, phenotyping, prenatal diagnosis, CT- measure lung density

Question 14

management

Answer 14

treatment for emphysema and liver disease. IV A1AT may prevent COPD exacerbations. liver transplant in decompensated cirrhosis.

Question 15

prognosis

Answer 15

some patients have life threatening symptoms in childhood others remain asymptomatic. worse prognosis if male, smoker, obese.

Question 16

what is the main cause of death

Answer 16

emphysema. liver disease in 5%