Alpha-1-Antitrypsin Deficiency

Alpha-1-antitrypsin is a glycoprotein produced primarily in the liver secreted under the influence of proinflammatory cytokines forming several globulins whose roles are to suppress additional tissue damage by neutralizing granulocyte elastase and proteinase primarily in the lung during infective and inflammatory process. Is responsible for protecting tissues against proteolytic damage by enzymes like neutrophil elastase and proteinase. It is also a tissue reparation inductor. Deficiency of alpha-1-antitrypsin (A1ATD) is a rare autosomal recessive co-dominant disorder most often seen in Northern European ancestry populations. A1ATD is the most common genetic cause of pediatric liver disease and transplantation. The defect in alpha-1-antitrypsin expression in the hepatocyte is followed by damage to the liver and/or lungs primarily. A1ATD can be asymptomatic or long-lasting and even permanently symptomatic depending in expression on the genotype and numerous exogenous factors such as infection, toxic or other damages to the liver and lungs. Liver damage occurs due to intrahepatocyte retention of alpha-1-antitrypsin and in the lung due to the lack of its protective effect. Early in life A1ATD causes a cholestatic syndrome, conjugated hyperbilirubinemia beyond the second week of life, associated with low birth weight and poor weight gain sometimes difficult to differentiate from biliary atresia. The liver damage is severe in only 1-2% of affected patients, most often has a slowly progressive character and juvenile cirrhosis develops in 15% of cases. In other organs A1ATD can cause pulmonary emphysema (chronic obstructive pulmonary disease), cytoplasmic anti-neutrophil cytoplasmic vasculitis and inflammatory necrotizing panniculitis in the skin. A1ATD individuals screened at birth who smoke develop COPD by age of 40 years. A1ATD is also associated with other diseases such as rheumatoid arthritis, sinusitis, nasal polyps, inflammatory bowel disease, peptic ulcer disease and diabetes. Management of A1ATD is limited. A diagnosis of A1ATD may have important implications including testing of family members, genetic counseling, smoking avoidance, avoidance of high risk occupations and consideration of augmentation therapy.

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