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Increased serum bile acid concentration

MedGen UID:
868605
Concept ID:
C4023004
Finding
HPO: HP:0012202

Definition

An increase in the concentration of bile acid in the blood. [from HPO]

Conditions with this feature

Autosomal recessive keratitis-ichthyosis-deafness syndrome
MedGen UID:
224809
Concept ID:
C1275089
Disease or Syndrome
Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR) is characterized by neonatal-onset ichthyotic erythroderma and profound sensorineural deafness, with failure to thrive and developmental delay in childhood. Severe corneal scarring with vision loss has been observed in adulthood. Low plasma copper and ceruloplasmin levels have been reported in some patients (Alsaif et al., 2019; Boyden et al., 2019). An autosomal dominant form of KID syndrome (KIDAD; 148210) is caused by mutation in the GJB2 gene (121011) on chromosome 13q12. Mutation in the AP1S1 gene (603531) causes a disorder with overlapping features (MEDNIK; 609313).
Neonatal intrahepatic cholestasis due to citrin deficiency
MedGen UID:
340091
Concept ID:
C1853942
Disease or Syndrome
Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.
Progressive familial intrahepatic cholestasis type 3
MedGen UID:
356333
Concept ID:
C1865643
Disease or Syndrome
The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.\n\nIn addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.\n\nThere are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.\n\nSigns and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).\n\nMost people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.\n\nProgressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.
Fanconi-Bickel syndrome
MedGen UID:
501176
Concept ID:
C3495427
Disease or Syndrome
Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose (Manz et al., 1987). Because no underlying enzymatic defect in carbohydrate metabolism had been identified and because metabolism of both glucose and galactose is impaired, a primary defect of monosaccharide transport across the membranes had been suggested (Berry et al., 1995; Fellers et al., 1967; Manz et al., 1987; Odievre, 1966). Use of the term glycogenosis type XI introduced by Hug (1987) is to be discouraged because glycogen accumulation is not due to the proposed functional defect of phosphoglucomutase, an essential enzyme in the common degradative pathways of both glycogen and galactose, but is secondary to nonfunctional glucose transport.
Congenital bile acid synthesis defect 5
MedGen UID:
904751
Concept ID:
C4225390
Congenital Abnormality
Any congenital bile acid synthesis defect in which the cause of the disease is a mutation in the ABCD3 gene.
Benign recurrent intrahepatic cholestasis type 1
MedGen UID:
1637492
Concept ID:
C4551899
Disease or Syndrome
The phenotypic spectrum of ATP8B1 deficiency ranges from severe through moderate to mild. Severe ATP8B1 deficiency is characterized by infantile-onset cholestasis that progresses to cirrhosis, hepatic failure, and early death. Although mild-to-moderate ATP8B1 deficiency initially was thought to involve intermittent symptomatic cholestasis with a lack of hepatic fibrosis, it is now known that hepatic fibrosis may be present early in the disease course. Furthermore, in some persons with ATP8B1 deficiency the clinical findings can span the phenotypic spectrum, shifting over time from the mild end of the spectrum (episodic cholestasis) to the severe end of the spectrum (persistent cholestasis). Sensorineural hearing loss (SNHL) is common across the phenotypic spectrum.
Trichohepatoneurodevelopmental syndrome
MedGen UID:
1648322
Concept ID:
C4748898
Disease or Syndrome
Trichohepatoneurodevelopmental syndrome is a complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and severe global developmental delay (Morimoto et al., 2018).
Hypercholanemia, familial 1
MedGen UID:
1781366
Concept ID:
C5542604
Disease or Syndrome
Familial hypercholanemia-1 (FHCA1) is an autosomal recessive disorder characterized by elevated concentrations of bile acids (usually conjugated), itching, and fat malabsorption, leading to poor overall growth and deficiencies of fat-soluble vitamins. Vitamin D deficiency results in rickets, and vitamin K deficiency results in a coagulopathy (Morton et al., 2000; Shneider et al., 1997; summary by Carlton et al., 2003). See also bile acid conjugation defect-1 (BACD1; 619232), which can also show increased bile acid levels, although the bile acids in BACD1 are unconjugated. Genetic Heterogeneity of FHCA See FHCA2 (619256), caused by mutation in the SLC10A1 gene (182396) on chromosome 14q24.
Hypercholanemia, familial, 2
MedGen UID:
1780531
Concept ID:
C5543243
Disease or Syndrome
Familial hypercholanemia-2 (FHCA2) is an autosomal recessive inborn error of metabolism characterized by persistently increased plasma levels of conjugated bile salts apparent from infancy. Most patients are asymptomatic and have no liver dysfunction, although some neonates may have transient jaundice or transiently elevated liver enzymes. These abnormalities improve with age. The bile acid defect can result in impaired absorption of fat-soluble vitamins, including D and K, causing decreased bone mineral density or prolonged prothrobin time (PT) (summary by Deng et al., 2016 and Liu et al., 2017). For a discussion of genetic heterogeneity of FHCA, see FHCA1 (607748).
Osteootohepatoenteric syndrome
MedGen UID:
1785846
Concept ID:
C5543557
Disease or Syndrome
Osteootohepatoenteric syndrome (OOHE) is characterized by a variable combination of bone fragility, hearing loss, cholestasis, and congenital diarrhea. Some patients also display mild developmental delay and intellectual disability (Esteve et al., 2018).
Cholestasis, progressive familial intrahepatic, 8
MedGen UID:
1794255
Concept ID:
C5562045
Disease or Syndrome
Progressive familial intrahepatic cholestasis-8 (PFIC8) is an autosomal recessive disorder characterized by cholestasis and high gamma-glutamyltransferase presenting in the infantile period (summary by Unlusoy Aksu et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600).
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
MedGen UID:
1794262
Concept ID:
C5562052
Disease or Syndrome
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis (NEDMSC) is an autosomal recessive disorder characterized by severely impaired global development apparent from infancy, progressive microcephaly, and neonatal cholestasis manifest as jaundice and elevated liver enzymes. The liver disease resolves, but affected individuals show feeding difficulties, failure to thrive, hypotonia, seizures, hyperkinetic movements, irritability, and poor eye contact or vision, and achieve almost no motor or cognitive developmental milestones. Brain imaging demonstrates agenesis or hypoplasia of the corpus callosum. Death in early childhood may occur (summary by Schneeberger et al., 2021).
Cholestasis, progressive familial intrahepatic, 10
MedGen UID:
1807702
Concept ID:
C5676981
Disease or Syndrome
Progressive familial intrahepatic cholestasis-10 (PFIC10) is an autosomal recessive liver disorder characterized by the onset of symptoms in the first months or years of life. Features include jaundice, pruritis, and hepatomegaly associated with increased serum bilirubin and bile acids. Liver transaminases may be variably increased, but gamma-glutamyltransferase (GGT; see 612346) is normal. Liver biopsy shows hepatocellular and canalicular cholestasis with giant cell changes. Although rare patients may have episodes of diarrhea and even show endoscopic features of microvillus inclusion disease (MVID), this tends to be transient and cholestasis dominates the clinical picture (Gonzales et al., 2017; Cockar et al., 2020). For a discussion of genetic heterogeneity of progressive familial intrahepatic cholestasis, see PFIC1 (211600).
Cholestasis, progressive familial intrahepatic, 11
MedGen UID:
1807308
Concept ID:
C5676985
Disease or Syndrome
Cholestasis, progressive familial intrahepatic, 12
MedGen UID:
1824084
Concept ID:
C5774311
Disease or Syndrome
Progressive familial intrahepatic cholestasis-12 (PFIC12) is characterized by neonatal-onset jaundice and conjugated hyperbilirubinemia, associated with intense pruritus. Transaminases are mildly elevated but GGT (see 612346) is normal. Hepatosplenomegaly and mildly prolonged activated partial thromboplastin time (APTT) have been observed in some patients (Qiu et al., 2019).

Professional guidelines

PubMed

van Wessel DBE, Thompson RJ, Gonzales E, Jankowska I, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipiński P, Czubkowski P, Rock N, Shagrani M, Broering D, Algoufi T, Mazhar N, Nicastro E, Kelly DA, Nebbia G, Arnell H, Björn Fischler, Hulscher JBF, Serranti D, Arikan C, Polat E, Debray D, Lacaille F, Goncalves C, Hierro L, Muñoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsőfi A, Calvo PL, Grabhorn E, Sturm E, van der Woerd WJ, Kamath BM, Wang JS, Li L, Durmaz Ö, Onal Z, Bunt TMG, Hansen BE, Verkade HJ; NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) consortium
J Hepatol 2020 Jul;73(1):84-93. Epub 2020 Feb 20 doi: 10.1016/j.jhep.2020.02.007. PMID: 32087350
Kremer AE, Namer B, Bolier R, Fischer MJ, Oude Elferink RP, Beuers U
Dig Dis 2015;33 Suppl 2:164-75. Epub 2015 Dec 7 doi: 10.1159/000440829. PMID: 26641452
Garg A
Am J Cardiol 1998 Feb 26;81(4A):47B-51B. doi: 10.1016/s0002-9149(98)00038-1. PMID: 9526814

Recent clinical studies

Therapy

Zhang Y, Liu L, Wei C, Wang X, Li R, Xu X, Zhang Y, Geng G, Dang K, Ming Z, Tao X, Xu H, Yan X, Zhang J, Hu J, Li Y
BMC Med 2023 May 5;21(1):174. doi: 10.1186/s12916-023-02880-0. PMID: 37147641Free PMC Article
Schneider KM, Candels LS, Hov JR, Myllys M, Hassan R, Schneider CV, Wahlström A, Mohs A, Zühlke S, Liao L, Elfers C, Kilic K, Henricsson M, Molinaro A, Hatting M, Zaza A, Drasdo D, Frissen M, Devlin AS, Gálvez EJC, Strowig T, Karlsen TH, Hengstler JG, Marschall HU, Ghallab A, Trautwein C
Nat Metab 2021 Sep;3(9):1228-1241. Epub 2021 Sep 22 doi: 10.1038/s42255-021-00452-1. PMID: 34552267
Xie G, Jiang R, Wang X, Liu P, Zhao A, Wu Y, Huang F, Liu Z, Rajani C, Zheng X, Qiu J, Zhang X, Zhao S, Bian H, Gao X, Sun B, Jia W
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Lütjohann D, Stellaard F, Kerksiek A, Lötsch J, Oertel BG
Eur J Clin Pharmacol 2021 May;77(5):659-669. Epub 2020 Nov 17 doi: 10.1007/s00228-020-03041-5. PMID: 33201347Free PMC Article
Wang X, Yang S, Li S, Zhao L, Hao Y, Qin J, Zhang L, Zhang C, Bian W, Zuo L, Gao X, Zhu B, Lei XG, Gu Z, Cui W, Xu X, Li Z, Zhu B, Li Y, Chen S, Guo H, Zhang H, Sun J, Zhang M, Hui Y, Zhang X, Liu X, Sun B, Wang L, Qiu Q, Zhang Y, Li X, Liu W, Xue R, Wu H, Shao D, Li J, Zhou Y, Li S, Yang R, Pedersen OB, Yu Z, Ehrlich SD, Ren F
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Prognosis

Bajaj JS, Fagan A, Gavis EA, Mousel T, Gallagher ML, Puri P, Fuchs M, Davis BC, Hylemon PB, Zhou H, Ahluwalia V, Cadrain R, Sikaroodi M, Gillevet PM
Hepatol Commun 2024 Feb 1;8(2) Epub 2024 Feb 3 doi: 10.1097/HC9.0000000000000384. PMID: 38315140Free PMC Article
Dolbnya AD, Popov IA, Pekov SI
Curr Top Med Chem 2024;24(8):722-736. doi: 10.2174/0115680266290367240130054142. PMID: 38303538
Nyholm I, Hukkinen M, Pihlajoki M, Davidson JR, Tyraskis A, Lohi J, Heikkilä P, Hänninen S, Andersson N, Eloranta K, Carpén O, Heikinheimo M, Davenport M, Pakarinen MP
Hepatology 2023 Apr 1;77(4):1263-1273. Epub 2023 Jan 3 doi: 10.1097/HEP.0000000000000048. PMID: 36692476Free PMC Article
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Front Endocrinol (Lausanne) 2022;13:898750. Epub 2022 Jul 22 doi: 10.3389/fendo.2022.898750. PMID: 35937832Free PMC Article
Schneider KM, Candels LS, Hov JR, Myllys M, Hassan R, Schneider CV, Wahlström A, Mohs A, Zühlke S, Liao L, Elfers C, Kilic K, Henricsson M, Molinaro A, Hatting M, Zaza A, Drasdo D, Frissen M, Devlin AS, Gálvez EJC, Strowig T, Karlsen TH, Hengstler JG, Marschall HU, Ghallab A, Trautwein C
Nat Metab 2021 Sep;3(9):1228-1241. Epub 2021 Sep 22 doi: 10.1038/s42255-021-00452-1. PMID: 34552267

Clinical prediction guides

Dolbnya AD, Popov IA, Pekov SI
Curr Top Med Chem 2024;24(8):722-736. doi: 10.2174/0115680266290367240130054142. PMID: 38303538
Zhang Y, Liu L, Wei C, Wang X, Li R, Xu X, Zhang Y, Geng G, Dang K, Ming Z, Tao X, Xu H, Yan X, Zhang J, Hu J, Li Y
BMC Med 2023 May 5;21(1):174. doi: 10.1186/s12916-023-02880-0. PMID: 37147641Free PMC Article
Schneider KM, Candels LS, Hov JR, Myllys M, Hassan R, Schneider CV, Wahlström A, Mohs A, Zühlke S, Liao L, Elfers C, Kilic K, Henricsson M, Molinaro A, Hatting M, Zaza A, Drasdo D, Frissen M, Devlin AS, Gálvez EJC, Strowig T, Karlsen TH, Hengstler JG, Marschall HU, Ghallab A, Trautwein C
Nat Metab 2021 Sep;3(9):1228-1241. Epub 2021 Sep 22 doi: 10.1038/s42255-021-00452-1. PMID: 34552267
Lütjohann D, Stellaard F, Kerksiek A, Lötsch J, Oertel BG
Eur J Clin Pharmacol 2021 May;77(5):659-669. Epub 2020 Nov 17 doi: 10.1007/s00228-020-03041-5. PMID: 33201347Free PMC Article
Jiao N, Baker SS, Chapa-Rodriguez A, Liu W, Nugent CA, Tsompana M, Mastrandrea L, Buck MJ, Baker RD, Genco RJ, Zhu R, Zhu L
Gut 2018 Oct;67(10):1881-1891. Epub 2017 Aug 3 doi: 10.1136/gutjnl-2017-314307. PMID: 28774887

Recent systematic reviews

Han X, Wang J, Wu Y, Gu H, Zhao N, Liao X, Jiang M
PLoS One 2024;19(7):e0305170. Epub 2024 Jul 25 doi: 10.1371/journal.pone.0305170. PMID: 39052638Free PMC Article
Manzotti C, Casazza G, Stimac T, Nikolova D, Gluud C
Cochrane Database Syst Rev 2019 Jul 5;7(7):CD012546. doi: 10.1002/14651858.CD012546.pub2. PMID: 31283001Free PMC Article
Giljaca V, Poropat G, Stimac D, Gluud C
Cochrane Database Syst Rev 2010 Jan 20;2010(1):CD004036. doi: 10.1002/14651858.CD004036.pub3. PMID: 20091555Free PMC Article

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