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INTRODUCTION

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There are a number of disorders of the liver that fit within the categories of genetic, metabolic, and infiltrative disorders (Table 367e-1). Inherited disorders include hemochromatosis, Wilson’s disease, α1 antitrypsin (α1AT) deficiency, and cystic fibrosis (CF). Hemochromatosis is the most common inherited disorder affecting white populations, with the genetic susceptibility for the disease being identified in 1 in 250 individuals. Over the past 15 years, it has become increasingly apparent that nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes found in the U.S. population. This disorder is discussed in greater detail in Chap. 364. Infiltrative disorders of the liver are relatively rare.

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TABLE 367e-1Genetic, Metabolic, and Infiltrative Diseases Affecting the Liver
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GENETIC LIVER DISEASES

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Hereditary Hemochromatosis

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Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism (Chap. 428). Our knowledge of the disease and its phenotypic expression has changed since 1996, when the gene for HH, called HFE, was identified, allowing for genetic testing for the two major mutations (C282Y and H63D) that are responsible for HFE-related HH. Subsequently, several additional genes/proteins involved in the regulation of iron homeostasis have been identified, contributing to a better understanding of cellular iron uptake and release and the characterization of additional causes of inherited iron overload (Table 367e-2).

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TABLE 367e-2Classification of Iron Overload Syndromes
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Most patients with HH are asymptomatic; however, when patients present with symptoms, they are frequently nonspecific and include weakness, fatigue, lethargy, and weight loss. Specific, organ-related symptoms include abdominal pain, arthralgias, and symptoms and signs of chronic liver disease. Increasingly, most patients are now identified before they have symptoms, either through family studies or from the performance of screening iron studies. Several prospective population studies have shown that C282Y homozygosity is found in about 1 in 250 individuals of northern European descent, with the heterozygote frequency seen in approximately 1 in 10 individuals. It is important to consider HH in patients who present with the symptoms ...

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