Book contents
- Frontmatter
- Contents
- Contributing Authors
- Preface to the Third Edition
- Preface to the First Edition
- SECTION I PATHOPHYSIOLOGY OF PEDIATRIC LIVER DISEASE
- SECTION II CHOLESTATIC LIVER DISEASES
- SECTION III HEPATITIS AND IMMUNE DISORDERS
- SECTION IV METABOLIC LIVER DISEASE
- 22 Laboratory Diagnosis of Inborn Errors of Metabolism
- 23 α1-Antitrypsin Deficiency
- 24 Cystic Fibrosis Liver Disease
- 25 Inborn Errors of Carbohydrate Metabolism
- 26 Copper Metabolism and Copper Storage Disorders
- 27 Iron Storage Disorders
- 28 Heme Biosynthesis and the Porphyrias
- 29 Tyrosinemia
- 30 The Liver in Lysosomal Storage Diseases
- 31 Disorders of Bile Acid Synthesis and Metabolism: A Metabolic Basis for Liver Disease
- 32 Inborn Errors of Mitochondrial Fatty Acid Oxidation
- 33 Mitochondrial Hepatopathies
- 34 Nonalcoholic Fatty Liver Disease
- 35 Peroxisomal Diseases
- 36 Urea Cycle Disorders
- SECTION V OTHER CONDITIONS AND ISSUES IN PEDIATRIC HEPATOLOGY
- Index
- Plate section
- References
23 - α1-Antitrypsin Deficiency
from SECTION IV - METABOLIC LIVER DISEASE
Published online by Cambridge University Press: 18 December 2009
Book contents
- Frontmatter
- Contents
- Contributing Authors
- Preface to the Third Edition
- Preface to the First Edition
- SECTION I PATHOPHYSIOLOGY OF PEDIATRIC LIVER DISEASE
- SECTION II CHOLESTATIC LIVER DISEASES
- SECTION III HEPATITIS AND IMMUNE DISORDERS
- SECTION IV METABOLIC LIVER DISEASE
- 22 Laboratory Diagnosis of Inborn Errors of Metabolism
- 23 α1-Antitrypsin Deficiency
- 24 Cystic Fibrosis Liver Disease
- 25 Inborn Errors of Carbohydrate Metabolism
- 26 Copper Metabolism and Copper Storage Disorders
- 27 Iron Storage Disorders
- 28 Heme Biosynthesis and the Porphyrias
- 29 Tyrosinemia
- 30 The Liver in Lysosomal Storage Diseases
- 31 Disorders of Bile Acid Synthesis and Metabolism: A Metabolic Basis for Liver Disease
- 32 Inborn Errors of Mitochondrial Fatty Acid Oxidation
- 33 Mitochondrial Hepatopathies
- 34 Nonalcoholic Fatty Liver Disease
- 35 Peroxisomal Diseases
- 36 Urea Cycle Disorders
- SECTION V OTHER CONDITIONS AND ISSUES IN PEDIATRIC HEPATOLOGY
- Index
- Plate section
- References
Summary
Homozygous PIZZ α1-antitrypsin (α1-AT) deficiency is a relatively common genetic disorder, affecting 1 in 1600 to 1 in 2000 live births [1, 2]. It is an autosomal codominant disorder associated with 85–90% reduction in serum concentrations of α1-AT. A single amino acid substitution results in an abnormally folded protein that is unable to traverse the secretory pathway. The mutant α1-ATZ protein is retained in the endoplasmic reticulum (ER) rather than secreted into the blood and body fluids.
α1-Antitrypsin is an approximately 55-kDa secretory glycoprotein that inhibits destructive neutrophil proteases, elastase, cathepsin G, and proteinase 3. Plasma α1-AT is derived predominantly from the liver and increases three- to fivefold during the host response to tissue injury or inflammation. It is the archetype of a family of structurally related circulating serine protease inhibitors called serpins.
Nationwide prospective screening studies done by Sveger [1, 3] in Sweden have shown that only 8–10% of the PIZZ population develops clinically significant liver disease over the first 20 years of life. Nevertheless, this deficiency is the most frequent genetic cause of liver disease in children and the most frequent genetic disease for which children undergo orthotropic liver transplantation. It also has been associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma in adults [4].
Although the condition does not affect children, many α1-AT-deficient individuals develop destructive lung disease and emphysema.
- Type
- Chapter
- Information
- Liver Disease in Children , pp. 545 - 571Publisher: Cambridge University PressPrint publication year: 2007
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