Alpha‐1‐Antitrypsin Deficiency

Alpha-1-Antitrypsin Deficiency

Kathleen M. Campbell, MD , Lee A. Denson, MD

Basic Information

Definition

Alpha-1-antitrypsin (A1AT) deficiency is an inherited autosomal recessive disease caused by homozygosity for the mutant type “Z” A1AT protein. A1AT deficiency is the most common genetic cause of liver disease in children and panacinar emphysema in adults.

ICD-9-CM Code

277.6 Alpha-1-antitrypsin deficiency

Epidemiology & Demographics

• The incidence of A1AT deficiency (PiZZ) in most populations is 1 in 1600 to 1 in 2000 live births.
• The prevalence of A1AT deficiency (PiZZ) in the United States is 1 in 4800; an additional 1 in 600 individuals is heterozygous for the Z allele.
• From 10% to 15% of all PiZZ homozygotes develop clinically significant liver disease during the first 30 years of life.
• Liver disease most commonly presents in infancy (as neonatal cholestasis), but may also present as chronic liver disease in childhood or adulthood.
• Neonatal cholestasis may be more common in males.
• Clinically significant pulmonary dysfunction is not apparent until the third decade of life.
• A1AT deficiency occurs worldwide and affects all major racial subgroups.
• Heterozygote carriers of A1AT deficiency (PiMZ) may be at increased risk for a number of other liver or lung diseases.

Clinical Presentation

• Persistent jaundice in infancy
• Late hemorrhagic disease in infancy
• Feeding difficulties
• Poor growth
• Pruritis
• Melena/hematemesis (from esophageal varices)
• Asymptomatic elevated transaminases
• Hepatomegaly or splenomegaly, or both
• Ascites (with advanced liver disease)
• Chronic cough, exercise intolerance, wheezing (not apparent until late in second decade of life)
• Increased anteroposterior diameter of chest, prolonged expiratory phase, clubbing, hyperresonant lung fields, poor air exchange (not apparent until late in second decade)
• Membranoproliferative glomerulonephritis, relapsing panniculitis, and systemic vasculitis associated with A1AT deficiency in adults

Etiology

• A1AT is a protease inhibitor that is produced primarily in the liver.
• A1AT deficiency results in synthesis of a defective A1AT protein that cannot be excreted from the hepatocytes.
• Liver disease is caused by accumulation of abnormal protein polymers in the hepatocytes; in some patients this may be aggravated by an additional defect in the ability to break down the abnormal protein.
• Lung disease (pulmonary emphysema) is caused by a lack of active A1AT in the lung, leading to uninhibited proteolytic destruction of the connective tissue backbone.
• The onset of lung disease is hastened and the severity of disease worsened by exposure to tobacco smoke.

Diagnosis

Differential Diagnosis

• Other causes of neonatal cholestasis (see Jaundice/Hyperbilirubinemia in Differential Diagnosis [Section II])

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Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Alpha‐1‐Antitrypsin Deficiency

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