α1-Antitrypsin Deficiency
DEFINITION:
Deficiency in alpha-1-antitrypsin (α1-AT) characterized by liver and/or lung injury
Other inheritable forms of liver disease: Hemochromatosis, Wilson’s
EPIDEMIOLOGY:
1 in 2,000 is homozygous and 1 in 30 is a heterozygous carrier (Z allele)
Causes neonatal hepatitis in 15-30% of children with ZZ phenotype
ETIOLOGIES:
Autosomal recessive
Gene is located on chromosome 14 (replacement of glutamic acid by lysine at 342 position), leading to deficiency in sialic acid
Abnormal α1-AT » polymerization in liver (cirrhosis) & uninhibited protease activity in lung (emphysema)
PATHOPHYSIOLOGY:
α1-AT is a protease inhibitor (enzyme) made in liver that helps to break down trypsin and other tissue proteases
Responsible for inhibiting trypsin, collagenase, and elastase; With α1-AT deficiency, these are left unopposed
Lungs: can lead to progressive decrease in elastin and development of premature emphysema (not same MOA as liver disease)
Liver: failure to secrete α1-AT, aggregates of the defective protein found (i.e. not true ‘deficiency’)
Unclear means to the development of cirrhosis
Over 75 different protease inhibitor (Pi) alleles have been identified:
M/M is normal (95% of population)
Z/Z results in lowest levels of α1-AT and this phenotype confirms the diagnosis
CLINICAL MANIFESTATIONS/PHYSICAL EXAM:
Adults and children with liver involvement have no symptoms until they develop signs and symptoms of chronic liver disease
Symptoms, other than liver, Emphysema: lower lung blebs (exacerbated markedly by smoking)
Consider α1-AT in any adult who presents with chronic hepatitis, cirrhosis, portal HTN, or HCC of unknown etiologyRelated posts:
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