KEGG   DISEASE: Hyperbilirubinemia
Entry
H00208                      Disease                                
Name
Hyperbilirubinemia
  Subgroup
Crigler-Najjar syndrome (CN) [DS:H02054]
Familial neonatal hyperbilirubinemia [DS:H02152]
Gilbert Syndrome [DS:H02055]
Dubin-Johnson syndrome (DJS) [DS:H02056]
Rotor syndrome (RS) [DS:H02057]
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
Brite
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Inborn errors of metabolism
    5C58  Inborn errors of porphyrin or heme metabolism
     H00208  Hyperbilirubinemia
Pathway
hsa04976  Bile secretion
hsa00860  Porphyrin metabolism
hsa02010  ABC transporters
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]
Other DBs
ICD-11: 5C58.0
ICD-10: E80.4 E80.5 E80.6
MeSH: D006932
OMIM: 218800 606785 143500 237900 237500 237450
Reference
  Authors
Bosma PJ
  Title
Inherited disorders of bilirubin metabolism.
  Journal
J Hepatol 38:107-17 (2003)
DOI:10.1016/S0168-8278(02)00359-8
Reference
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
Reference
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
Reference
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
LinkDB

ยป Japanese version

DBGET integrated database retrieval system