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
Human diseases [BR:br08402]
 Digestive system diseases
  Liver diseases
   H00624  Familial cholestasis
 Other congenital disorders
  Ribosomopathies
   H00624  North American Indian childhood cirrhosis (NAIC)
Human diseases in ICD-10 classification [BR:br08403]
 11. Diseases of the digestive system (K00-K93)
  K80-K87  Disorders of gallbladder, biliary tract and pancreas
   K83  Other diseases of biliary tract
    H00624  Familial cholestasis
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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