Alpha-1-Anti-Trypsin deficiency

From Iusmgenetics

Contents 1 Alpha-1-Anti-Trypsin deficiency 1.1 General background information 1.2 Mode of inheritance 1.3 Single important gene 1.4 Etiology 1.5 Pathogenesis 1.6 Phenotypic information 1.7 Diagnosis 1.8 Treatment 1.9 Recent research 1.10 5 important facts 1.11 Not to be confused with 1.12 Questions and answers

Alpha-1-Anti-Trypsin deficiency

General background information

Mode of inheritance

• Alpha-1-anti-trypsin deficiency is autosomal recessive
• Incidence of "ZZ" genotype is 1/2500 Caucasians

Single important gene

• AAT
• A serine protease inhibitor
• Major function is to inhibit elastase
  • Elastase is made by neutrophils
  • Elastase will eventually destroy lung tissue if not treated
• AAT is highly polymorphic

• There are two disease-causing alleles:
  • "S" allele produces a protein with only 50-60% activity
  • "Z" allele produces a protein with only 10-15% activity
  • Null alleles produce no activity at all and the most severe disease form
  • "M" allele is normal

Etiology

Pathogenesis

• Pts with A1ATD are at a 20-fold higher risk of developing emphysema
  • 80-90% eventually develop emphysema

Phenotypic information

• MM, MS, and SS genotypes manifest no disease
• SZ have an increased chance of developing emphysema
• ZZ have the full disease state

• Smokers develop disease earlier in life and with greater severity
• ZZ pts develop liver disease in addition to pulmonary fibrosis
  • Liver disease develops from mutant protein aggregates

Diagnosis

Treatment

• AAT-inhibitor injections
• Liver transplant for ZZ or null mutant pts
• Gene therapy one of these days?

Recent research

5 important facts

Not to be confused with

Questions and answers