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Metabolic liver disease has
traditionally referred to diseases that result from inborn errors
of metabolism. These disorders are due to a single enzyme defect
that affects the synthesis or catabolism of a carbohydrate (CHO),
protein, or lipid. These defects in metabolism can result in either
liver failure or cirrhosis, with or without injury to other tissues,
or relative sparing of the liver with primary toxicity to other
organ systems (Table 28–1). Metabolic disorders that arise
in the liver with primary toxicity to other organ systems are not
addressed in this chapter. This chapter approaches metabolic-induced
liver disease not only from the traditional approach, those resulting
from a single enzyme defect, but also as a genetic susceptibility
induced by a trigger, such as a drug or a metabolic derangement
associated with visceral obesity (nonalcoholic fatty liver disease
(NAFLD)).
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Taken individually, single enzyme defects are rare, although
as a group they constitute at least 10% of pediatric liver
transplantations. Wilson’s disease, alpha-1-antitrypsin
deficiency (A1AT), and cystic fibrosis are the most common inherited
metabolic conditions that affect the liver and are discussed individually
in this textbook. Fortunately, in children most drug-induced liver
disease (DILI) remains uncommon, although certain pediatric patient
populations are at increased risk. NAFLD is becoming a worldwide
problem of childhood and is the most common cause of liver disease
in this age group. The increase in prevalence parallels the epidemic
of obesity.1 This chapter will address the following three
categories of metabolic liver disease in separate sections: inherited
metabolic-induced liver disease, DILI, and obesity-induced NAFLD.
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Enzymatic disorders that cause liver disease include disorders
of CHO, protein, lipid/microsomal, and bile acid synthesis.
Because the pathogenesis of these disorders is directly related
to the metabolic pathway where the defect occurs, each class of
disorders is addressed ...