| H00208 | |
| H number | H00208 |
| Name | Hyperbilirubinemia |
| Description | Gilbert disease and Crigler-Najjar syndromes result in unconjugated hyperbilirubinemia caused by deficiency of bilirubin-UDP-glucuronosyltransferase which is involved in the detoxification of bilirubin by conjugation with glucuronic acid. Gilbert disease is a benign familial disorder characterized by low-grade chronic hyperbilirubinemia, while Crigler-Najjar syndromes are more severe by kernicterus and jaundice. Dubin-Johnson syndrome (DJS) is caused by mutations in ABCC2, a canalicular bilirubin glucuronide and xenobiotic export pump. Rotor syndrome (RS) is caused by mutations in the SLCO1B1 and SLCO1B3 genes that encode organic anion transporters. In both DJS and RS, mild jaundice begins shortly after birth or in childhood. There are no signs of hemolysis, and routine hematologic and clinical-biochemistry test results are normal, aside from the primarily conjugated hyperbilirubinemia. The hepatocyte pigment deposits are typical of DJS. Total urinary excretion of coproporphyrins is greatly increased in RS. |
| Category | Inherited metabolic disorder |
| Network | - |
| Gene | (CN1, CN2) UGT1A1 [HSA:54658] [KO:K00699] (DJS) ABCC2 [HSA:1244] [KO:K05666] (RS) SLCO1B1 [HSA:10599] [KO:K05043] (RS) SLCO1B3 [HSA:28234] [KO:K05043] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 5C58.0 ICD-10: E80.4 E80.5 E80.6 MeSH: D006932 OMIM: 218800 606785 143500 237900 237500 237450 |
| Reference | PMID:12480568 AUTHORS Bosma PJ TITLE Inherited disorders of bilirubin metabolism. JOURNAL J Hepatol 38:107-17 (2003) DOI:10.1016/S0168-8278(02)00359-8 PMID:16386929 (UGT1A1) AUTHORS Costa E TITLE Hematologically important mutations: bilirubin UDP-glucuronosyltransferase gene mutations in Gilbert and Crigler-Najjar syndromes. JOURNAL Blood Cells Mol Dis 36:77-80 (2006) DOI:10.1016/j.bcmd.2005.10.006 PMID:12388192 (ABCC2) AUTHORS Keitel V, Nies AT, Brom M, Hummel-Eisenbeiss J, Spring H, Keppler D TITLE A common Dubin-Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2). JOURNAL Am J Physiol Gastrointest Liver Physiol 284:G165-74 (2003) DOI:10.1152/ajpgi.00362.2002 PMID:22232210 (SLCO1B1, SLCO1B3) AUTHORS van de Steeg E, Stranecky V, Hartmannova H, Noskova L, Hrebicek M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, Kenworthy KE, Sticova E, al-Edreesi M, Knisely AS, Kmoch S, Jirsa M, Schinkel AH TITLE Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. JOURNAL J Clin Invest 122:519-28 (2012) DOI:10.1172/JCI59526 |