KEGG   DISEASE: Familial cholestasisHelp
H00624                      Disease                                

Familial cholestasis, including:
Progressive familial intrahepatic cholestasis (PFIC);
Benign recurrent intrahepatic cholestasis (BRIC);
Intrahepatic cholestasis of pregnancy (ICP);
North American Indian childhood cirrhosis (NAIC)
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.
Inherited metabolic disease; Liver disease
Human diseases [BR:br08402]
 Digestive system diseases
  Liver diseases
   H00624  Familial cholestasis
 Other congenital disorders
   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
ABC transporters
Bile secretion
Primary bile acid biosynthesis
Ribosome biogenesis in eukaryotes
(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]
(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
Rifampicin [DR:D00211]
Cholestyramine [DR:D02690]
Ursodeoxycholic acid [DR:D00734]
Other DBs
van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH
Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy.
Best Pract Res Clin Gastroenterol 24:541-53 (2010)
Jansen PL, Sturm E
Genetic cholestasis, causes and consequences for hepatobiliary transport.
Liver Int 23:315-22 (2003)
PMID:11067870 (PFIC4)
Schwarz M, Wright AC, Davis DL, Nazer H, Bjorkhem I, Russell DW
The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis.
J Clin Invest 106:1175-84 (2000)
Roma MG, Toledo FD, Boaglio AC, Basiglio CL, Crocenzi FA, Sanchez Pozzi EJ
Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications.
Clin Sci (Lond) 121:523-44 (2011)
Hofmann AF
Rifampicin and treatment of cholestatic pruritus.
Gut 51:756-7 (2002)
Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A
A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis.
Am J Hum Genet 71:1443-9 (2002)
Drouin E, Russo P, Tuchweber B, Mitchell G, Rasquin-Weber A
North American Indian cirrhosis in children: a review of 30 cases.
J Pediatr Gastroenterol Nutr 31:395-404 (2000)

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