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PFIC1
MCID: CHL132
MIFTS: 53
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Cholestasis, Progressive Familial Intrahepatic, 1 (PFIC1)
Categories:
Cancer diseases, Endocrine diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Rare diseases
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MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 1:
Characteristics:Orphanet epidemiological data:59
progressive familial intrahepatic cholestasis type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; OMIM:57
Inheritance:
autosomal recessive
Miscellaneous:
onset in early infancy genetic heterogeneity, see also pfic2 , pfic3 caused by a defect in bile acid transport allelic disorder to benign recurrent intrahepatic cholestasis (bric1, ) allelic disorder to intrahepatic cholestasis of pregnancy (icp, ) HPO:32
cholestasis, progressive familial intrahepatic, 1:
Onset and clinical course infantile onset Inheritance autosomal recessive inheritance Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Cancer diseases Anatomical: Liver diseases Gastrointestinal diseases Endocrine diseases
ICD10:
34
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NIH Rare Diseases
:
53
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79306Disease definitionPFIC1, a type of progressive familial intrahepathic cholestasis (PFIC, see this term), is an infantile hereditary disorder in bile formation that is hepatocellular in origin and associated with extrahepatic features.EpidemiologyEstimated prevalence at birth of PFIC types 1-3 varies between 1/50,000 and 1/100,000 births. PFIC1 is the less frequent type of PFIC.Clinical descriptionIts onset occurs mostly during infancy. Clinical signs of cholestasis (discolored stools, dark urine) usually appear in the first months of life with recurrent or permanent jaundice associated with hepatomegaly and severe pruritus. Patients usually develop fibrosis and end-stage liver disease before adulthood. Extrahepatic features have been reported including persistent short stature, watery diarrhea, pancreatitis and sensorineural deafness.EtiologyPFIC1 is due to mutations in the ATP8B1 gene (18q21-22) encoding the FIC1 protein expressed at the canalicular membrane of hepatocytes as well as in other epithelia. In hepatocytes, abnormal protein might indirectly disrupt biliary bile acid secretion, explaining the low biliary bile acid concentration found in PFIC1 patients. Extrahepatic features of the disease are probably related to the extrahepatic expression of FIC1.Diagnostic methodsPFIC1 should be suspected in children with a clinical history of cholestasis of unknown origin after exclusion of the other main causes of cholestasis presenting with normal serum gamma-GT activity and high serum bile acid concentration. Usually, serum alpha-fetoprotein level is normal and alanine aminotransferase values are below five times the upper limit of normal. Liver ultrasonography is usually normal but may reveal a huge gallbladder. Liver histology reveals canalicular cholestasis and the absence of true ductular proliferation with only periportal biliary metaplasia of hepatocytes. When performed, cholangiography shows a normal biliary tree and allows bile collection. Biliary lipid analysis reveals mildly decreased biliary bile salt concentration. Genotyping confirms the diagnosis.Differential diagnosisIn the scope of cholestasis with normal gamma-GT, differential diagnosis includes mainly primary bile acid synthesis defects and PFIC2 (see these terms).Antenatal diagnosisPrenatal diagnosis can be proposed if a mutation has been identified in each parent.Genetic counselingTransmission is autosomal recessive.Management and treatmentUrsodeoxycholic acid therapy (UDCA) should be initiated in all patients to prevent liver damage but is not fully effective. Rifampicin is helpful to control pruritus. Nasobiliary drainage may help to select potential responders to biliary diversion. However, because of severe cholestasis, half of patients are ultimately candidates for liver transplantation (LT). Diarrhea often worsens after LT and might be favorably managed by bile adsorptive resin treatment. LT does not prevent extrahepatic progression of the disease, and does not lead to catch-up growth. Furthermore, severe steatohepatitis of the liver graft has been reported. Specialized follow-up is mandatory lifelong. FIC1 defect predisposes to development of intrahepatic cholestasis of pregnancy (see this term).Visit the Orphanet disease page for more resources.
MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 1, also known as byler disease, is related to cholestasis, progressive familial intrahepatic, 4 and cholestasis, progressive familial intrahepatic, 3, and has symptoms including pruritus, diarrhea and icterus. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 1 is ATP8B1 (ATPase Phospholipid Transporting 8B1), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Synthesis of bile acids and bile salts. The drugs Pharmaceutical Solutions and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and pancreas, and related phenotypes are failure to thrive and splenomegaly Disease Ontology : 12 A progressive familial intrahepatic cholestasis characterized by autosomal recessive inheritance that has material basis in mutation in the ATP8B1 gene on chromosome 18q21. OMIM : 57 Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood (Alonso et al., 1994; Whitington et al., 1994; Klomp et al., 2004). (211600) UniProtKB/Swiss-Prot : 75 Cholestasis, progressive familial intrahepatic, 1: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. Wikipedia : 76 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more... |
Symptoms via clinical synopsis from OMIM:57Clinical features from OMIM:211600Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 1:32 (show all 11)
UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic, 1:pruritus, diarrhea, icterus GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 1 according to GeneCards Suite gene sharing:26
MGI Mouse Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 1:46
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Drugs for Cholestasis, Progressive Familial Intrahepatic, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):(show all 21)
Interventional clinical trials:(show all 15)
Cochrane evidence based reviews: cholestasis, progressive familial intrahepatic 1 |
MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic, 1:41
Liver,
Bone,
Pancreas
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Articles related to Cholestasis, Progressive Familial Intrahepatic, 1:(show all 16)
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Genes related to Cholestasis, Progressive Familial Intrahepatic, 1 (3 elite genes):(show all 11) - Elite gene
- Cancer Census gene in COSMIC
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UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 1:75 (show all 17)
ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 1:6 (show top 50) (show all 86)
Cosmic variations for Cholestasis, Progressive Familial Intrahepatic, 1:9
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for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic, 1.
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Pathways related to Cholestasis, Progressive Familial Intrahepatic, 1 according to GeneCards Suite gene sharing:
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Cellular components related to Cholestasis, Progressive Familial Intrahepatic, 1 according to GeneCards Suite gene sharing:
Biological processes related to Cholestasis, Progressive Familial Intrahepatic, 1 according to GeneCards Suite gene sharing:(show all 17)
Molecular functions related to Cholestasis, Progressive Familial Intrahepatic, 1 according to GeneCards Suite gene sharing:
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