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KERNICTERUS IN AN ADULT WITH CRIGLER-NAJJAR SYNDROME TYPE II TREATED WITH PLASMA EXCHANGE
H Patel1, D Wong2, H Shah2
1Faculty of Medicine, University of Toronto; 2Department of Medicine, Division of Gastroenterology, University Health Network, Toronto, Ontario
Aims: Unconjugated hyperbilirubinemia is observed in a spectrum of inherited disorders. Crigler-Najjar Syndrome (CNS) is a rare autosomal recessive disorder that yields an abnormal form of urinediphosphoglucuronyltransferase (UGT) that has no activity (Type I) or limited activity (Type II).
Methods: We present a case of a 48-year-old man with CNS Type II with recurrent kernicterus. He was jaundiced at birth and continued to have bilirubin >300umol/L with improvement on phenobarbitol enzyme induction therapy. At age 12, the patient developed kernicterus post appendectomy with bilirubin reaching 720umol/L and generalized tonic-clonic seizures. EEG was consistent with metabolic encephalopathy. Phototherapy and plasma exchange was initiated with symptomatic improvement. Severe caloric restriction resulted in the rise in bilirubin. A liver biopsy demonstrated that UGT activity was present at 9% of normal. The bilirubin remained between 300-400umol/L.
Results: In June 2008 the patient underwent total knee athroplasty and was discharged 3 days later with a poor appetite but continued to take phenobarbitol. He was re-admitted 2 days later with fever, confusion, and hallucinations leading to obtundation over 4 days. The peak bilirubin was 654umol/L from a baseline of 320umol/L. Elevated liver enzymes (AST 222U/L, ALT 265U/L, and ALP 113U/L) and decrease in albumin of 33g/L were noted. Investigations revealed normal CT head, spinal fluid analysis, knee aspirate, electrolytes, and thyroid function. A liver biopsy showed changes consistent with an acute and chronic cholestatic process but no inflammation or steatosis was seen. Multiple generalized tonic-clonic seizures were witnessed that were controlled with Keppra and Clobazam. EEG was suggestive of metabolic encephalopathy. MRI of the brain revealed hyperintensity of the basal ganglia due to bilirubin deposition or stroke. The patient was thought to have kernicterus and underwent eight sessions of plasma exchange after which his level of consciousness improved. He remains on long-term phenobarbitol with serum bilirubin stabilized at 344umol/L however he is left with expressive aphasia. After complete investigations for structural or metabolic causes of encephalopathy, it was felt that the caloric restriction post-surgery led to the significant rise in bilirubin and kernicterus.
Conclusions: This patient developed kernicterus as a result of a series of events that led to an increase in serum unconjugated bilirubin and decrease in albumin. When patients with CNS Type II develop an acute illness or are peri-operative, maintaining adequate caloric intake, normal serum albumin levels, and continuing enzyme induction therapy with phenobarbitol can minimize the risk of kernitcterus.