Alpha one Antitrypsin Deficiency in ICU

Abstract

Alpha 1-antitrypsin deficiency is a genetic disorder that causes defective production of alpha 1-antitrypsin (A1AT), leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT proteinin liver cells. There are several forms and degrees of deficiency; the form and degree depend on whether the sufferer has one or two copies of the defective allele because it is a co-dominant trait. Severe A1AT deficiency causes panacinaremphysema or COPD in adult life in many people with the condition (especially if they are exposed to cigarette smoke). The disorder can lead to various liver diseases in a minority of children and adults, and occasionally more unusual problems. Symptoms of alpha-1 antitrypsin deficiency include shortness of breath, wheezing, rhonchi, and rales. The patient's symptoms may resemble recurrent respiratory infections or asthma that does not respond to treatment. Individuals with A1AD may developemphysema during their thirties or forties even without a history of significant smoking, though smoking greatly increases the risk for emphysema. A1AD causes impaired liver function in some patients and may lead to cirrhosis and liver failure (15%). In newborns, alpha-1 antitrypsin deficiency has indicators that include early onset jaundice followed by prolonged jaundice. It is a leading indication for liver transplantation in newborns. As protein electrophoresis does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a nephelometric or immunoturbidimetric method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analysed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient. A1AT deficiency is treated through avoidance of damaging inhalants and, in severe cases, by intravenous infusions of the A1AT protein or bytransplantation of the liver or lungs. It usually produces some degree of disability and reduces life expectancy. A1AD patients may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms.