Crigler-Najjar Syndrome, Type I

Crigler-Najjar Syndrome, Type I is a rare inherited disorder that affects the body's ability to process a substance called bilirubin, which is produced when red blood cells break down. This condition primarily involves the liver, which normally helps remove bilirubin from the blood. In people with this syndrome, bilirubin builds up to very high levels, causing a yellowing of the skin and eyes known as jaundice. The excess bilirubin can also affect the brain, leading to a serious condition called kernicterus. This disorder usually appears soon after birth and requires careful medical attention because of the risk of brain damage. The main problem is a missing or nonfunctional enzyme that normally helps the liver process bilirubin.

Crigler-Najjar Syndrome, Type I is a severe autosomal recessive disorder characterized by a complete absence of the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is essential for the conjugation and clearance of unconjugated bilirubin. This leads to persistent, severe unconjugated hyperbilirubinemia from birth, with serum bilirubin levels often exceeding 20 mg/dL. The condition results from mutations in the UGT1A1 gene, causing a total loss of enzyme activity. Clinically, it presents with profound jaundice and a high risk of kernicterus, a form of bilirubin-induced neurological damage. Unlike Type II, Type I does not respond to phenobarbital, which induces residual enzyme activity. The disease is life-threatening without aggressive management to prevent bilirubin neurotoxicity.