INTRODUCTION AND DEFINITIONS
Jaundice is a yellowish discoloration of the skin and sclerae that indicates an abnormality of bilirubin metabolism or excretion. The bilirubin can be either unconjugated, in which case it is poorly soluble in water, or conjugated to glucuronic acid, which makes it soluble in water; conjugated bilirubin is also known as "direct" bilirubin. Disorders causing unconjugated hyperbilirubinemia are more common in children, and tend to be distinct from those causing conjugated hyperbilirubinemia. However, some diseases increase both unconjugated and conjugated bilirubin because they affect several different aspects of hepatocyte function.
Beyond the neonatal period, the normal serum total bilirubin concentration is less than 1 mg/dL (17 micromol/L), of which approximately 96 percent is present in unconjugated form. Jaundice usually becomes clinically apparent when the serum bilirubin concentration is greater than 2 mg/dL (34 micromol/L), which is twice the upper limit of normal.
Conjugated hyperbilirubinemia is defined by a serum conjugated bilirubin concentration greater than 1 mg/dL (17 micromol/L) if the total bilirubin is <5 mg/dL (85 micromol/L) or more than 20 percent of the total bilirubin if the total bilirubin is >5 mg/dL (85 micromol/L). It is an abnormal finding that requires further evaluation. The differential diagnosis of conjugated hyperbilirubinemia in neonates differs from that in older children and adults, and is discussed in separate topic reviews. (See "Approach to neonatal cholestasis" and "Classification and causes of jaundice or asymptomatic hyperbilirubinemia", section on 'Disorders associated with conjugated hyperbilirubinemia'.)
This topic will present an overview of the causes of unconjugated hyperbilirubinemia in children and infants beyond the neonatal period and discuss the evaluation of such patients. Management varies with the underlying disease.
The evaluation of unconjugated hyperbilirubinemia in neonates and the causes and diagnostic approach for the adult with jaundice, which are somewhat different, are discussed separately. (See "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants" and "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia" and "Classification and causes of jaundice or asymptomatic hyperbilirubinemia".)