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Alpha 1-antitrypsin deficiency
Insights
Alpha-1 Antitrypsin Deficiency (AATD) causes liver disease in children and emphysema in adults. Replacement therapy with human alpha 1-protease inhibitor may halt lung damage in AATD patients.
Area of Science:
- Biochemistry
- Genetics
- Pulmonology
Background:
- Alpha-1 Antitrypsin (AAT) is a polymorphic protein, with common alleles M, S, and Z.
- Alpha-1 Antitrypsin Deficiency (AATD) results from inherited AAT variants, leading to abnormal protein accumulation and reduced serum levels.
- AATD is linked to pediatric liver disease and adult-onset emphysema, exacerbated by smoking.
Purpose of the Study:
- To review the pathophysiology and current therapeutic strategies for Alpha-1 Antitrypsin Deficiency.
- To evaluate the efficacy of replacement therapy in managing AATD-associated pulmonary damage.
Main Methods:
- Review of existing literature on AATD genetics, clinical manifestations, and treatment options.
- Analysis of data regarding the effectiveness of Prolastin (human alpha 1-protease inhibitor) in AATD patients.
Main Results:
- Infants with PiZZ genotype have significantly reduced AAT serum concentrations (approx. 16% of normal).
- Weekly intravenous Prolastin administration aims to maintain serum AAT levels above 80 mg/dl, showing promise in arresting pulmonary damage.
- The impact of Prolastin on AATD-related liver disease remains undetermined. Early results of aerosolized recombinant alpha 1-protease inhibitor are promising.
Conclusions:
- AATD is an inherited metabolic disorder with significant pulmonary and hepatic consequences.
- Intravenous replacement therapy with human alpha 1-protease inhibitor appears effective in halting lung damage progression in AATD.
- Further research is needed to ascertain the effects on liver disease and explore novel delivery methods like aerosolized inhibitors.
Abstract:
alpha 1-Antitrypsin (AAT) is a polymorphic protein with many variants collectively known as the Pi system. The most common alleles are the M, S and Z, which are co-dominantly inherited. Infants with PiZZ have approximately 16% of the normal AAT serum concentration. alpha 1-Antitrypsin deficiency (AATD) is an inborn error of metabolism which is principally associated with liver disease in children and emphysema in young adulthood. Individuals with AATD produce an abnormal protein which accumulates in the liver, resulting in decreased serum levels. Affected individuals cannot protect their lungs from digestion by elastase. Smoking is a significant risk factor for the early development of emphysema. Prolastin, human alpha 1-protease inhibitor, is now available as replacement therapy. Weekly intravenous administration, with the goal of maintaining the serum AAT greater than 80 mg/dl, appears to arrest pulmonary damage. Its effect on liver disease is unknown at this time. A recombinant alpha 1-protease inhibitor is being tested in aerosol form with promising early results.