Crigler-Najjar syndrome in Saudi Arabia

Area of Science:

• Hepatology
• Genetics
• Pediatrics

Background:

• Crigler-Najjar syndrome is a rare genetic disorder.
• It causes severe unconjugated hyperbilirubinemia due to absent or severely deficient UDP-glucuronosyltransferase (UGT1A1) enzyme activity.
• This leads to a high risk of bilirubin-induced brain damage (kernicterus).

Purpose of the Study:

• To highlight the critical need for early diagnosis and appropriate management of Crigler-Najjar syndrome.
• To present clinical data from a cohort of patients diagnosed with CN syndrome.
• To discuss treatment outcomes and the impact of newer therapies like liver transplantation.

Main Methods:

• Retrospective review of 12 patients diagnosed with Crigler-Najjar syndrome between 1986 and 1994.
• Analysis of clinical presentation, diagnostic methods (including liver biopsy and enzyme activity assays), and treatment responses.
• Evaluation of outcomes, including kernicterus development and the role of phototherapy, phenobarbital, and liver transplantation.

Main Results:

• Jaundice was noted within days of birth in most cases; one delayed diagnosis led to kernicterus.
• Phenobarbital monotherapy was ineffective, underscoring disease severity.
• Phototherapy was required for all patients, with six needing combination therapy; five developed kernicterus.
• Liver biopsies showed minimal/focal cholestasis in most, with near-complete UDPGT deficiency in seven patients.
• One patient successfully underwent living-related segmental liver transplantation.

Conclusions:

• Crigler-Najjar syndrome is a potentially fatal condition necessitating prompt diagnosis and management.
• Early intervention is crucial to prevent neurological complications like kernicterus.
• Liver transplantation represents a significant advancement, offering a cure and eliminating the need for intensive phototherapy.