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Crigler-Najjar syndrome

INTRODUCTION

The metabolism of bilirubin by the liver comprises four distinct but interrelated stages (algorithm 1). (See "Bilirubin metabolism".)

  • Uptake from the circulation
  • Intracellular storage
  • Conjugation with glucuronic acid
  • Biliary excretion

Normally, approximately 96 percent of serum bilirubin is unconjugated. Abnormalities in any one or more of the above steps can result in hyperbilirubinemia in which there is either an elevation in unconjugated bilirubin alone or of both unconjugated and conjugated bilirubin. Complex clinical disorders, such as hepatitis or cirrhosis, can affect multiple processes, resulting in the accumulation of both unconjugated and conjugated bilirubin. In these settings, the proportion of conjugated bilirubin in plasma increases. In contrast, the unconjugated fraction alone is increased with bilirubin overproduction (as with hemolysis) without liver disease and with inherited or acquired disorders that specifically affect bilirubin uptake or glucuronidation. (See "Classification and causes of jaundice or asymptomatic hyperbilirubinemia".)

The most common causes of unconjugated hyperbilirubinemia are bilirubin overproduction, Gilbert's syndrome, and neonatal jaundice. This topic review will discuss unconjugated hyperbilirubinemia due to the rare inherited Crigler-Najjar syndromes. The other disorders are presented separately as is an approach to the patient with jaundice. (See appropriate topic reviews).

CLASSIFICATION

Crigler-Najjar syndrome, also referred to as congenital nonhemolytic jaundice with glucuronosyltransferase deficiency, is a rare, autosomal recessive disorder of bilirubin metabolism. It has been divided into two distinct forms (types I and II) based upon the severity of the disease (table 1).
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