This protocol addresses Crigler-Najjar syndrome type 1 (CNS1) presenting with severe unconjugated hyperbilirubinemia, confirmed complete absence of UGT1A1 enzymatic activity, no significant response to a phenobarbital trial, and a high risk of kernicterus. CNS1 is characterised by total loss of UGT1A1 activity — unlike the milder type 2 form — producing persistently critical bilirubin levels and leaving the patient at serious neurological risk.
The prior management step was plasmapheresis combined with an anion-exchange resin (bilirubin-adsorbent column), initiated at the first signs of bilirubin encephalopathy. This approach did not achieve the required temporary reduction in serum bilirubin levels — the criterion that triggers escalation to this next protocol.
When strategies aimed at temporarily lowering circulating bilirubin are no longer sufficient, the next step is a definitive surgical intervention that permanently restores bilirubin metabolism. Several procedural options exist; the choice among them depends on donor organ availability and the individual patient's circumstances. The complete decision algorithm, timing guidance, and procedural selection criteria are in the full protocol.
Normalization of total serum bilirubin levels and restored bilirubin metabolism.
DOI: 10.3390/ijms252011006
Type I disease (CNS1) is characterized by severe jaundice and a high risk of neurologic sequelae (kernicterus), resulting from the complete absence of enzymatic activity; type II disease (CNS2) is a milder form with decreased enzyme activity, lower serum bilirubin levels, and little to no risk of kernicterus.
Patients with CNS1 do not respond to phenobarbital and require long-term phototherapy to keep serum bilirubin levels within safe limits.
In CNS1, there is a complete loss of UGT1A1 activity due to deletions, insertions, missense mutations, or premature stop codons, resulting in severe unconjugated hyperbilirubinemia.
Liver transplantation (LT) is currently the only definitive treatment for CNS1.
The choice between orthotopic, auxiliary, or living-related liver transplantation depends on the availability of donor organs and the individual circumstances of the patient.
The child's total bilirubin level increased to 742.0 µmol/L before the operation, but post-transplant, bilirubin levels normalized, and mental function recovered without further signs of neurological damage.
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