Cholestasis, Progressive Familial Intrahepatic, 1 (PFIC1)

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Disease Ontology 12 DOID:0070226 OMIM 56 211600 OMIM Phenotypic Series 56 PS211600 MeSH 43 C535933 D002780 MESH via Orphanet 44 C535933

ICD10 via Orphanet 33 K76.8 Orphanet 58 ORPHA79306 MedGen 41 C0268312 C4551898 SNOMED-CT via HPO 68 16294009 18165001 197494007 19943007 237836003 237837007 258211005 267060006 279333002 36440009 418290006 418363000 422065006 424492005 432788009 62315008 80515008 9326001 more UMLS 71 C0268312 C1865643

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79306 Definition PFIC1, 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. Epidemiology Estimated 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 description Its 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. Etiology PFIC1 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 methods PFIC1 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 diagnosis In the scope of cholestasis with normal gamma-GT, differential diagnosis includes mainly primary bile acid synthesis defects and PFIC2 (see these terms). Antenatal diagnosis Prenatal diagnosis can be proposed if a mutation has been identified in each parent. Genetic counseling Transmission is autosomal recessive . Management and treatment Ursodeoxycholic 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 cholestasis, progressive familial intrahepatic 1, 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 Cardiac conduction. The drugs Glycerol and Estrogens have been mentioned in the context of this disorder. Affiliated tissues include liver and lung, and related phenotypes are splenomegaly and hepatomegaly

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 : ⁵⁶ 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 : ⁷³ 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 : ⁷⁴ Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Clinical features from OMIM:

211600

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