Dataset Information

Genetics of familial intrahepatic cholestasis syndromes.

ABSTRACT: Bile acids and bile salts have essential functions in the liver and in the small intestine. Their synthesis in the liver provides a metabolic pathway for the catabolism of cholesterol and their detergent properties promote the solubilisation of essential nutrients and vitamins in the small intestine. Inherited conditions that prevent the synthesis of bile acids or their excretion cause cholestasis, or impaired bile flow. These disorders generally lead to severe human liver disease, underscoring the essential role of bile acids in metabolism. Recent advances in the elucidation of gene defects underlying familial cholestasis syndromes has greatly increased knowledge about the process of bile flow. The expression of key proteins involved in bile flow is tightly regulated by transcription factors of the nuclear hormone receptor family, which function as sensors of bile acids and cholesterol. Here we review the genetics of familial cholestasis disorders, the functions of the affected genes in bile flow, and their regulation by bile acids and cholesterol.

SUBMITTER: van Mil SW

PROVIDER: S-EPMC1736078 | biostudies-other | 2005 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Genetics of familial intrahepatic cholestasis syndromes.

van Mil S W C SW Houwen R H J RH Klomp L W J LW

Journal of medical genetics 20050601 6

Bile acids and bile salts have essential functions in the liver and in the small intestine. Their synthesis in the liver provides a metabolic pathway for the catabolism of cholesterol and their detergent properties promote the solubilisation of essential nutrients and vitamins in the small intestine. Inherited conditions that prevent the synthesis of bile acids or their excretion cause cholestasis, or impaired bile flow. These disorders generally lead to severe human liver disease, underscoring ...[more]

PMID: 15937079

Similar Datasets

Project description:BackgroundProgressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure. For children and their parents, PFIC is an extremely distressing disease. Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance.MethodsDatabases including MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.ResultsThree systematic reviews and twenty-two studies were eligible for inclusion for the epidemiology of PFIC including a total of 2603 patients. Study periods ranged from 3 to 33 years. Local population prevalence of PFIC was reported in three studies, ranging from 9.0 to 12.0% of children admitted with cholestasis, acute liver failure, or splenomegaly. The most detailed data come from the NAPPED study where native liver survival of >15 years is predicted in PFIC2 patients with a serum bile acid concentration below 102 µmol/L following bile diversion surgery. Burden of disease was mainly reported through health-related quality of life (HRQL), rates of surgery and survival. Rates of biliary diversion and liver transplant varied widely depending on study period, sample size and PFIC type, with many patients have multiple surgeries and progressing to liver transplant. This renders data unsuitable for comparison.ConclusionUsing robust and transparent methods, this systematic review summarises our current knowledge of PFIC. The epidemiological overview is highly mixed and dependent on presentation and PFIC subtype. Only two studies reported HRQL and mortality results were variable across different subtypes. Lack of data and extensive heterogeneity severely limit understanding across this disease area, particularly variation around and within subtypes.

Dataset Information

Genetics of familial intrahepatic cholestasis syndromes.

Publications

Genetics of familial intrahepatic cholestasis syndromes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets