A -Antitrypsin

Deficiency of aj-antitrypsin is also implicated in one type of liver disease (a,-antitrypsin deficiency liver... 

Figure 50-6. Scheme illustrating (A) normal inactivation of elastase by a,-antitrypsin and (B) situation in which the amount of a,-antitrypsin is substantially reduced, resulting in proteolysis by elastase and leading to tissue damage. 

Figure 50-7. Scheme of causation of a,-antitrypsin-deficiency iiver disease. The mutation shown causes formation of PiZZ (MiM 107400). (a,-AT, a,-antitrypsin.)... 

A third autosomal recessive genetic disease is a -antitrypsin deficiency. Abnormalities in the a,-antitrypsin protein impair secretion from the liver, a,-Antitrypsin deficiency causes cirrhosis in children as well as adults adults usually have concomitant pulmonary disease such as chronic obstructive pulmonary disease. 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

T. Ferkol, F. Mularo, J. Hilliard, S. Lodish, J. C. Perales, A. Ziady, and M. Konstan, Transfer of the human a-antitrypsin gene into pulmonary macrophages in vivo, Am. J. Respir. Cell. Mol. Biol., 18 (1998) 591-601. 

Determination of acute-phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgA, IgG, IgM), compressive markers (albumin, fibrinogen), markers of tissue destruction (Apo A-I, A-II, Apo B), components of complement (C3, C4), proteinase inhibitors (antithrombin HI, a -antitrypsin). The measurement was performed simultaneously in CSF and in serum (plasma) by a laser nephelometric method. The functional state of the blood-CSF barrier was evaluated numerically with the help of the quotient Q = Albcsp/s and also by the intrathecal synthesis of immunoglobulins according to Reiber s formula and for each class—IgG, IgM, IgA. 

Obtain a precast SDS-polyacrylamide slab gel or prepare one according to instructions in Experiment 4. The recommended gel is 12°/o acrylamide with a thickness of 0.75 mm. Protein samples are prepared as follows Purified proteins (transferrin, bovine serum albumin, a, -antitrypsin, a-lactalbumin from Experiment 4, and molecular weight standards) are supplied in Tris buffer, pH 6.8 solutions at a concentration of 1 mg/mL. Sera samples have been diluted and are ready for use. Prepare protein samples for electrophoresis in 0.5-mL microcentrifuge tubes with attached caps. Label the tubes from 1 to 5 as below or per your Instructor s directions. 

Toxicity resulting from exposure to cigarette smoke in persons afflicted with a -antitrypsin deficiency has been mentioned above (section 1.3). Avoiding cigarette smoke can prevent its destructive effects on the lungs, which result in emphysema and chronic obstructive lung disease.(9)... 

Antithrombin is a member of the SERPIN superfamily of proteins, which includes the inhibitors a2 an1 Pbsniin, ar antichymotrypsin, and a -proteinase inhibitor (79). Antithrombin is considered to be the primary inhibitor of coagulation (80) and targets most coagulation proteases as well as the enzymes trypsin, plasmin, and kallikrein (81). Inhibition takes place when a stoichiometric complex between the active site serine of the protease and the ARG393-SER394 bond of antithrombin forms (82,83), The tertiary structure of antithrombin resembles a,-antitrypsin in that it is folded into N-terminal domain helices and (3-sheets. This tertiary structure is maintained by the formation of three disulfide bonds (71). Four glycosylation sites exist on human... 

Factor deficiencies include disorders of fibrinogen such as afibrinogenemia and dysfibrinogenemias, prothrombin deficiency, factor V VII, X, XI, XII, and XIII deficiency, prekallikrein and high-molecular-weight kininogen deficiency, combined factor deficiencies, a2 anti-plasmin deficiency, a] antitrypsin Pittsburgh, and protein Z deficiency. 

This patient illustrates a complicated clinical course of oq-antitrypsin deficiency. Our patient had liver disease that presented during infancy and developed into hepatic cirrhosis. He exhibited most of the complications of cirrhosis, including portal hypertension with ascites, hyperammonemia, malnutrition, and variceal hemorrhage. These complications of cirrhosis are not unique to a,-antitrypsin deficiency, but it is important to note the potential severity of the liver disease associated with this condition. 

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