Case Presentation: The patient is a 22-year-old female with known history of Crigler-Najjar Syndrome Type 2, diagnosed in infancy. Both parents are recessive carriers of the UGT1A1 gene missense mutation. Her symptoms are typically well-maintained at home with intermittent phototherapy and nightly phenobarbital. The patient reports her baseline bilirubin levels are typically ~8 mg/dL. The patient underwent robotic laparoscopic cholecystectomy 5 days prior to admission. She now presents with 2 days of recurrent epigastric abdominal pain radiating to LUQ and bilateral flanks, nausea, and anorexia. The patient also noted a singular episode of non-bloody, nonbilious emesis. Pain was noted to be worse after attempting to eat, with no palliation. Pertinent medical history includes mononucleosis diagnosed 1 month prior to admission with clinical resolution. Upon presentation, her vital signs were BP 110/55 mmHg, HR 70 bpm, T 36.6 oC, respirations 16, LMP 26 days prior, SpO2 98% on RA. Other significant physical exam findings included ill appearance, abdominal tenderness, epigastric pain with radiation into RUQ/LUQ, and jaundice with scleral icterus. Lab values drawn in the ED were significant for AST 226 U/L, ALT 294 U/L, alkaline phosphatase 343 U/L, and total bilirubin 12.8 mg/dL. CBC, CMP, and coagulation profile were unremarkable. An abdominal & pelvic CT with contrast was consistent with uncomplicated prior cholecystectomy. An intraoperative cholangiogram from 5 days prior to admission was reviewed again with concern for distal defect. The patient underwent endoscopic retrograde cholangiopancreatography with sphincterotomy and clearance of stone debris. Occlusion cholangiogram showed no additional filling defect. The patient’s symptoms resolved, and there was improvement in LFTs including both total and direct bilirubin, returning to the patient’s personal baseline.
Discussion: Crigler-Najjar (CN) Syndrome Type II is a rare autosomal recessive genetic disorder which causes a significant elevation in unconjugated bilirubin due to deficient UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity. In most cases, other liver function tests are normal. Total bilirubin concentrations are typically, but not always, lower in patients with CN type II. The variation between CN types II and I is a result of residual UGT1A1 activity in type II. The primary treatment of CN Syndrome Type II is phenobarbital induction, which can induce this residual activity and reduce the serum bilirubin concentration by more than 25%. This result is not appreciated in patients with Type I disease. Stone formation is 40-50% more common in patients with CN Syndrome. Chronic cholestasis is also a known risk factor in this population. Stone pathology such as choledocholithiasis may often be overlooked as the cause of bilirubin elevation in patients with underlying hepatobiliary disorders. These pigmented stones are rarely found in the gallbladder, but rather in other parts of the biliary tree. It is helpful when patients are familiar with cholestatic patterns. Any change in this pattern or concern for ductal dilatation on imaging should raise concern for secondary obstruction.
Conclusions: This case highlights the importance of considering all causes of hyperbilirubinemia when managing patients with both acute pathology and chronic hepatic conditions such as Crigler-Najjar Syndrome. Prompt diagnosis, appropriate intervention and a well-rounded approach are paramount in achieving favorable outcomes.