α1anti trypsin deficiency

Alpha-1 antitrypsin (A1AT) is a glycoprotein which is largely produced in the liver

Autosomal dominent

SERPINA 1 gene (chromosome 14) > 100 allelic versions
A1AT is a serine protease inhibitor, protects tissues from enzymes released from inflammatory cells eg neutrophil elastase Normal range 1.5-3g/l (can increase with acute inflammation)

Genetic varients:

–MM:Normal (100%)
–MS/MZ: Carrier (60-80%)
–SS: Homozygote (60%)
–SZ:Heterozygote (40%)
–ZZ:Homozygote (10%), 15-30% liver disease, 75% emphysema
–Null variants:Completely lack A1AT (emphysema only)

Presentation:

Emphysema (unchecked neutrophil elastase)Cirrhosis (accumulation of insoluble protein within RER hepatocytes), most common cause paediatric liver transplantPanniculitis (painful cutaneous nodules at sites of trauma)

Diagnosis:

α1AT levelsGenotypingBiopsy: PAS + diastase resistant globules

 liver tissue showing magenta globules of retained, defective a anti-trypsin

Management:

Avoid smoking & ETOH
Injection / inhalation recombinant A1AT if emphysema predominates (experimetal)
gene therapyTransplant (does not recur in graft)