A 9-month-old infant who suffered bouts of jaundice and was diagnosed with severe nonhemolytic icterus shortly after birth has died of kernicterus. During the periods of jaundice, serum analysis showed an increased concentration of indirectreacting bilirubin with no detection of conjugated bilirubin. The premature death and early clinical findings in this infant suggest which of the following disorders?

Question

Quizplus · Accepted Answer

Crigler-Najjar syndrome, type 1 is characterized by severe unconjugated hyperbilirubinemia due to a deficiency in the enzyme UDP-glucuronosyltransferase, leading to kernicterus and early death.  Jaundice is caused by an elevation in the circulating levels of bilirubin, the heme degradation by-product. Bilirubin, which is toxic, is rendered harmless by binding to albumin in the serum and by conjugation to glucuronate in the liver. Profound hyperbilirubinemia leads to encephalopathy (kernicterus), which results in death if untreated. The hepatic conjugation of bilirubin to glucuronate is catalyzed by bilirubin-UDP-glucuronyltransferase (UGT). The conjugated form of bilirubin is less toxic due to its increased solubility. Hyperbilirubinemia can be of 2 types, unconjugated or conjugated. Defects in UGT will lead to unconjugated hyperbilirubinemia. The deficiency of UGT in Crigler-Najjar syndrome type I is complete (due to loss of coding exons in the UGT gene) and as a consequence affected individuals will die from the profound kernicterus.

A 9-Month-Old Infant Who Suffered Bouts of Jaundice and Was