CRIGLER-NAJJAR SYNDROME - I

 

CRIGLER-NAJJAR SYNDROME - I

 

DEFINITION:

An inherited disorder of bilirubin metabolism resulting in chronic, severe unconjugated hyperbilirubinemia and jaundice.

EPIDEMIOLOGY:

  • incidence: rare (about 70 cases reported)
  • age of onset:
    • newborn (2nd to 3rd week of life)
  • risk factors:
    • familial - autosomal recessive
      • chrom.#: 1q21-q23
      • gene: UDP-glucuronosyltransferase
    • M = F

PATHOGENESIS:

1. Background

  • UDP-glucuronosyltransferase is an enzyme which conjugates bili-rubin in the liver
  • there are two forms of Crigler-Najjar Syndrome based upon the degree of UDP-glucuronosyltrasferase deficiency:
  • Type I: severe form
  • Type II: mild-moderate form (also called Gilbert Syndrome)

2. Genetic Defect

  • genetic defect -> reduced UDP-glucuronosyltransferase activity -> persistent unconjugated hyperbilirubinemia -> toxic effect of unconjugated bilirubin on tissues (i.e., CNS -> kernicterus)

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

  • persistent icterus and jaundice
  • pale yellow stools

2. Neurological Manifestations

  • 1. Kernicterus
    • presents in the newborn period in 75% of cases
    • eventually develops in all patients despite therapy
  • INVESTIGATIONS:

    1. Serum

    • unconjugated hyperbilirubinemia
    • normal AST, ALT, alkaline phosphatase, bile salts

    2. Biopsy (Closed)

  • 1. Liver

    • occasional canalicular "bile plugs"
  • 3. Diagnostic

    • deficiency of UDP-glucuronsyltransferase activity in hepatic samples

    MANAGEMENT:

    1. For Hyperbilirubinemia

    • chronic phototherapy
    • exchange transfusions

    2. Surgery

    • liver transplantation

     

     

     

     

    Pediatric Database - CRIGLER-NAJJAR SYNDROME - I

    Pediatric Organization - Pedbase [at] Gmail.com