ALPHA-1 ANTITRYPSIN (A1AT) DEFICIENCY
This is an autosomal codominate condition that results in inadequate levels of A1AT. A1AT is an acute phase alpha-1 globulin synthesized by cells (most notably the hepatocyte and lung tissue) for protection against tissue injury. This is a normal response to preserve a balance within the body between cellular proteinases and the proteinase inhibitor. Tissue destruction may occur from released proteases when the individual fails to respond with an adequate compensatory synthesis and transport of the protease inhibitor alpha-1 antitrypsin to the site of injury.
A1AT deficiency may present with respiratory disease due to development of panlobular emphysema. Deficiency results in an inability to inactivate neutrophil elastase, leading to destruction of elastin in the walls of lung alveoli with resultant pulmonary emphysema in adults. A1AT deficiency may also become apparent as liver disease any time from birth to adulthood. At birth, or a few months thereafter, it can be discovered as a result of laboratory evidence of abnormal liver function or overt hepatitis with cholestatic jaundice. Later, in adolescence, it may take the forms of hepatitis or cirrhosis. In other instances it may remain quiescent until cirrhosis appears in the mid to older age groups. The prevalence of this deficiency is relatively common (1:2000) and detection is simple. The routine evaluation of any child with chronic liver disease should include a serum alpha-1 antitrypsin level. Severe deficiency is less frequently detected in adults with chronic liver disease. Instead, in adults, deficiency is more often associated with pulmonary emphysema and later in life with cirrhosis. The degree of deficiency correlates with the severity of the disease. Persons with severe deficiency (<30% of normal) may manifest premature emphysema. In contrast, persons with deficiency of 30 to 65% of normal are at an increased risk to develop emphysema only if they smoke. Persons with A1AT levels greater than 60% of normal do not manifest an increased tendency to develop emphysema.
Prolastin is a partially purified form of alpha antitrypsin that may be administered intravenously at weekly intervals. This treatment is expensive and the benefits are unproved; therefore, patient selection for therapy should be critical. Hepatitis B vaccination is recommended prior to the initiation of therapy. Patients should be encouraged to abstain from cigarette smoking and offered genetic counseling, and family members should be screened. Also, as persons with this disorder are at an increased risk for hepatocellular carcinoma (HCC), they should undergo regular screening of the serum alpha-feto protein and hepatic ultrasonography to detect any cancerous development.