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| Disease found: | Crigler-Najjar Syndrome |
| Current as of: | Mon Sep 16 2024 |
| Disease Overview: | Complete (Type I) or partial (Type II) deficiency in UGT1A1 leading to build up of unconjugated bilirubin. [more info] |
| Signs and Symptoms: | Type I: Persistent neonatal jaundice; risk of kernicterus (bilirubin encephalopathy) within first month, causing lethargy, hypotonia with episodes of spasticity, convulsions, and risk of lasting brain damage. Type II: milder, jaundice during concurrent illnesses, and rarely kernicterus. [more info] |
| Diagnosis: | Clinically: neonatal jaundice with high unconjugated bilirubin levels without hemolysis. Confirm via genetic testing for mutations in the UGT1A1 gene. [more info] |
| Treatment: | Phototherapy, plasmapheresis. Type II may show improved UGT1A1 activity with phenobarbital. Liver transplant is a definitive treatment and is often necessary if a patient stops responding to phototherapy (common as skin thickens with age); some believe transplant should be performed preventatively at an earlier age. [more info] Isolated hepatocyte transplant may be a "bridge" while waiting for whole-organ treatment. [more info] |
| Clinical Management: | Phototherapy must be provided indefinitely unless liver transplant provided; compliance with aggressive phototherapy can be difficult. Patients at increased risk for gallstones, liver fibrosis. Kernicterus is life-threatening, requires immediate phototherapy and transfer to ICU. Thresholds for bilirubin levels by gestational age here. Monitor total and direct serum bilirubin at least every 2 hours; monitor for anemia. Obtain blood type as exchange transfusion may be necessary to restore normal bilirubin levels. Additional considerations here. There is ongoing uncertainty about when to offer liver transplant; discuss patient preferences early [more]. Patients and families may get support from the American Liver Foundation or Parents of Infants and Children with Kernicterus |
| Referral: | Pediatric hepatology, gastroenterology, and genetic counseling is recommended. There are no centers dedicated to treating Crigler-Najjar Syndrome. Referral to Medical Genetics Department, if available. TeleRare Health for virtual care and consults is also recommended. |
| Clinical Trials: | Two trials are recruiting in Europe. Gene therapy with AAV has recently completed Phase 1, 2 studies. |