KEGG   DISEASE: H00624Help
Entry
H00624                      Disease                                

Name
Familial cholestasis, including:
Progressive familial intrahepatic cholestasis (PFIC);
Benign recurrent intrahepatic cholestasis (BRIC);
Intrahepatic cholestasis of pregnancy (ICP);
North American Indian childhood cirrhosis (NAIC)
Description
Familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by intrahepatic cholestasis, which can be divided in three main groups based on phenotypical differences: progressive familial intrahepatic cholestasis (PFIC), benign recurrent intrahepatic cholestasis (BRIC) and intrahepatic cholestasis of pregnancy (ICP). PFIC type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ATP8B1 and ABCB11 can also result in the less severe phenotype of BRIC type 1 and 2, respectively, while heterozygous mutations in all three genes are associated with ICP. PFIC type 4 is caused by mutations in HSD3B7,and also known as congenital bile acid synthesis defect type 1. North American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of familial cholestasis found in aboriginal children from northwestern Quebec. It has reported that a missense mutation in Cirhin causes NAIC. Cirhin/UTP4 is known to be required for ribosome biogenesis.
Category
Inherited metabolic disease; Liver disease
BRITE hierarchy
Pathway
ABC transporters
Bile secretion
Primary bile acid biosynthesis
Ribosome biogenesis in eukaryotes
Gene
(PFIC1/BRIC1/ICP) ATP8B1 [HSA:5205] [KO:K01530]
(PFIC2/BRIC2/ICP) ABCB11 [HSA:8647] [KO:K05664]
(PFIC3/ICP) ABCB4 [HSA:5244] [KO:K05659]
(PFIC4) HSD3B7 [HSA:80270] [KO:K12408]
(NAIC) CIRH1A [HSA:84916] [KO:K14548]
Marker
(Common) Elevated serum bile salts
(ATP8B1 deficiency) Coarse granular bile (electron microscopy)
(ABCB11 deficiency) Filamentous bile (electron microscopy), Giant cell hepatitis
(ABCB4 deficiency) Elevated serum gamma-glutamyl transpeptidase, Ductular proliferation
Drug
Rifampicin [DR:D00211]
Cholestyramine [DR:D02690]
Ursodeoxycholic acid [DR:D00734]
Other DBs
Reference
  Authors
van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH
  Title
Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy.
  Journal
Best Pract Res Clin Gastroenterol 24:541-53 (2010)
Reference
  Authors
Jansen PL, Sturm E
  Title
Genetic cholestasis, causes and consequences for hepatobiliary transport.
  Journal
Liver Int 23:315-22 (2003)
Reference
PMID:11067870 (PFIC4)
  Authors
Schwarz M, Wright AC, Davis DL, Nazer H, Bjorkhem I, Russell DW
  Title
The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis.
  Journal
J Clin Invest 106:1175-84 (2000)
Reference
  Authors
Roma MG, Toledo FD, Boaglio AC, Basiglio CL, Crocenzi FA, Sanchez Pozzi EJ
  Title
Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications.
  Journal
Clin Sci (Lond) 121:523-44 (2011)
Reference
  Authors
Hofmann AF
  Title
Rifampicin and treatment of cholestatic pruritus.
  Journal
Gut 51:756-7 (2002)
Reference
  Authors
Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A
  Title
A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis.
  Journal
Am J Hum Genet 71:1443-9 (2002)
Reference
  Authors
Drouin E, Russo P, Tuchweber B, Mitchell G, Rasquin-Weber A
  Title
North American Indian cirrhosis in children: a review of 30 cases.
  Journal
J Pediatr Gastroenterol Nutr 31:395-404 (2000)

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