Disorders of bilirubin clearance
Lorenza Matarazzo1, Federica Ferrari2, Giuseppe Maggiore2,3
1Pediatria, Grande Ospedale Metropolitano Niguarda, Milano 2IRCCS Ospedale Pediatrico Bambino Gesù, Roma 3Dipartimento di Scienze Mediche, Università di Ferrara
Hyperbilirubinemia can be due to increased production (hemolysis), reduced clearance or both. In newborns and infants, the activity of all enzymes is markedly reduced, contributing to the “physiological” neonatal jaundice. Bilirubin conjugation disorders are caused by mutations in UGT1A1 gene, responsible for decreased enzymatic activity (Gilbert’s and Crigler-Najjar type 2 syndromes) until complete absence (Crigler-Najjar type 1 syndrome). For Crigler-Najjar syndromes, therapy is based on aggressive phototherapy to reduce bilirubin levels <10 mg/dL and phenobarbital administration which stimulates the genomic expression of UGT1A1. Among biliary excretion disorders, Dubin-Johnson syndrome can have a variable onset with mild/moderate jaundice usually in asymptomatic adult patients and without evidence of chronic cholestatic liver disease. Rotor syndrome is a benign condition due to a defect in the sinusoidal re-uptake of conjugated bilirubin and characterized by asymptomatic mixed hyperbilirubinemia generally starting in childhood. In both conditions, diagnosis can be suspected by urinary coproporphyrins analysis.