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A1AT-Deficiency

α1AT Deficiency: Pathophysiology and Clinical Findings Authors: Sean Spence Reviewers: Danny Guo Yan Yu Merna Adly Crystal Liu Sam Lee* * MD at time of publication Abnormal α1-Anti-Trypsin (α1AT) allele(s) Accumulation of mutant α1AT protein as ordered polymers in endoplasmic reticulum of hepatocytes ↓ α1AT inhibition of Hepatocyte Injury tissue proteases (Mechanism unclear) ↓ release from hepatocytes Cirrhosis, chronic hepatitis, hepatocellular carcinoma ↓ lung elasticity, ↓ ability for lung to expel air on expirationà gas trapping, hyperinflation, airway collapse over time Role of Genetics: Low serum α1AT In the skin: Subcutaneous proteases > Anti- proteases Unopposed proteolysis in subcutaneous tissues Panniculitis (Rare, most cases associates with ZZ Genotype) Lung Proteases > Anti-proteases àproteolytic destruction of lung parenchymaàpanacinar emphysema (accelerated by smoking) Stigmata of chronic liver disease (ascites, jaundice, spider nevi, petechiae, etc.) Symptoms of chronic obstructive pulmonary disease (COPD): barrel chest/High residual volume (RV), low vital capacity (VC), wheezes on auscultation, etc) – see relevant slide Degree of α1AT deficiency dependent on genotype: • MM gives normal α1AT levels • MZ genotype produces levels ~ 35% of normal • ZZ genotype produces severe deficiency ( <10% of normal) • Null phenotype is completely deficient of α1AT N.B. Heterozygotes almost never develop phenotypic α1AT deficiency syndromes. Even some homozygotes don’t manifest the disease. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published January 12, 2020 on www.thecalgaryguide.com

کمبود-آلفا-یک-آنتیتریپسین-α1at

!مبود آلفا +ک آن.ت321س 56 α1AT