Pathophysiology
1) autosomal recessive inability of liver to conjugate bilirubin 2) type 1 – more severe; enzyme that conjugates bilirubin is completely inactive 3) type 2 – less severe clinically; some enzyme activity and partial bilirubin conjugation
Signs and Symptoms
1) type 1 with jaundice, kernicterus if untreated 2) type 2 has fairly normal development with some neurological deficits
Characteristic Test Findings
Laboratory – 1) high serum levels (20-45 mg/dL) of unconjugated bilirubin in both type 1 and 2 2) normal level of transaminases and alkaline phosphatase
Histology/Gross Pathology
1) bile – in type 1 is colorless; in type 2 is colored 2) liver parenchyma in type 1 is grossly normal except for occasional bile plugs
Biochemistry
1) deficient enzyme is hepatic glucruonyl transferase due to deficit in UGT1 gene 2) type 1 has a complete deficiency 3) type 2 has a partial deficiency
Treatment
1) type 1 – phototherapy (12h/day) or liver transplantation with tin protoporphyrin to ameliorate tranient bilirubin spikes 2) type 2 – daily phenobarbital
Tips for USMLE
1) best way to differentiate between types – administer phenobarbital 2) type 1 – phenobarbital does not induce microsomal enzymes, including glucuronyl transferase and does not decrease the unconjugated bilirubin 3) type 2 – phenobarbital causes a decrease in unconjugated bilirubin but never to normal levels 4) in type 1, jaundice occurs but urine is never dark-colored
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