Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of
lung disease, primarily
emphysema.
Emphysema results from the breakdown of lung matrix
elastin by
proteases, including
neutrophil elastase, a
protease normally inhibited by AAT. AATD also predisposes to
liver (cirrhosis) and skin (
panniculitis) disease, and to
vasculitis. The prevalence of AATD is estimated to be approximately 1 in 3,500 individuals in the United States. However, lack of awareness of AATD among some physicians, misperceptions regarding the absence of effective
therapy, and the close overlap in symptoms with
asthma and non-AATD
chronic obstructive pulmonary disease are thought to contribute to under-recognition of the disease. In patients with AATD, treatment with intravenous AAT augmentation
therapy is the only currently available treatment known to slow the progression of
emphysema. Moreover, smoking cessation and other lifestyle interventions also help improve outcomes. Early diagnosis and intervention are of key importance due to the irreversible nature of the resultant
emphysema.
Liver disease is the second leading cause of death among patients with AATD and a minority of patients present with
panniculitis or
antineutrophil cytoplasmic antibody-associated
vasculitis, thought to be directly related to AATD. Though no randomized trial has assessed the effectiveness of augmentation
therapy for AATD-associated
panniculitis, clinical experience and case series suggest there is a benefit. Other diseases putatively linked to AATD include aneurysmal disease and multiple neurological conditions, although these associations remain speculative in nature.