Evaluation of jaundice caused by unconjugated hyperbilirubinemia in children
- Oranit Shaked, MD
Oranit Shaked, MD
- Assistant Professor, Pediatrics
- Wertheim College of Medicine
- Barbara M Peña, MD, MPH
Barbara M Peña, MD, MPH
- Research Director
- Miami Children's Hospital
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 evaluation of cholestasis in neonates and young infants" 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".)
- Berk PD, Wolkoff AW, Berlin NI. Inborn errors of bilirubin metabolism. Med Clin North Am 1975; 59:803.
- Chowdhury JR, Chowdhury NR, Moscioni AD, et al. Differential regulation by triiodothyronine of substrate-specific uridinediphosphoglucuronate glucuronosyl transferases in rat liver. Biochim Biophys Acta 1983; 761:58.
- GREENBERGER NJ, MILLIGAN FD, DEGROOT LJ, ISSELBACHER KJ. JAUNDICE AND THYROTOXICOSIS IN THE ABSENCE OF CONGESTIVE HEART FAILURE. A STUDY OF FOUR CASES. Am J Med 1964; 36:840.
- Zhang D, Chando TJ, Everett DW, et al. In vitro inhibition of UDP glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos 2005; 33:1729.
- Perera MA, Innocenti F, Ratain MJ. Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: are we there yet? Pharmacotherapy 2008; 28:755.
- Mandl, KD. Jaundice-Unconjugated Hyperbilirubinemia. In: Textbook of Pediatric Emergency Medicine, Fleisher, GR, Ludwig, S, Henretig, FM (Eds), Lippincott, Williams & Wilkins, Philadelphia 2006. p. 399.
- Rubaltelli FF, Gourley GR, Loskamp N, et al. Transcutaneous bilirubin measurement: a multicenter evaluation of a new device. Pediatrics 2001; 107:1264.
- National newborn screening status report. Available at: http://www.nlm.nih.gov/medlineplus/newbornscreening.html (Accessed October 29, 2008).
- Black M, Billing BH. Hepatic bilirubin udp-glucuronyl transferase activity in liver disease and gilbert's syndrome. N Engl J Med 1969; 280:1266.
- Auclair C, Hakim J, Boivin P, et al. Bilirubin and paranitrophenol glucuronyl transferase activities of the liver in patients with Gilbert's syndrome An attempt at a biochemical breakdown of the Gilbert's syndrome. Enzyme 1976; 21:97.
- Rudenski AS, Halsall DJ. Genetic testing for Gilbert's syndrome: how useful is it in determining the cause of jaundice? Clin Chem 1998; 44:1604.
- INTRODUCTION AND DEFINITIONS
- CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA
- Bilirubin overproduction
- - Extravascular hemolysis
- - Intravascular hemolysis
- - Other
- Impaired hepatic bilirubin uptake
- - Reduced hepatic blood flow
- - Drugs
- Impaired bilirubin conjugation
- - Gilbert syndrome
- - Crigler-Najjar syndrome
- - Hyperthyroidism
- - Drugs
- - Other
- DIAGNOSTIC APPROACH
- HISTORY AND PHYSICAL EXAMINATION
- Physical examination
- LABORATORY TESTING
- Anemia and/or hemolysis
- Absence of anemia or hemolysis
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS