U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Conjugated hyperbilirubinemia

MedGen UID:
82787
Concept ID:
C0268307
Disease or Syndrome
Synonyms: Direct hyperbilirubinemia; Hyperbilirubinemia, conjugated; Hyperbilirubinemia, direct
SNOMED CT: Conjugated hyperbilirubinemia (9326001)
 
HPO: HP:0002908

Definition

Abnormally high level of conjugated bilirubin in the blood. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVConjugated hyperbilirubinemia

Conditions with this feature

Dubin-Johnson syndrome
MedGen UID:
7181
Concept ID:
C0022350
Disease or Syndrome
Dubin-Johnson syndrome is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function (summary by Wada et al., 1998).
Rotor syndrome
MedGen UID:
67435
Concept ID:
C0220991
Disease or Syndrome
Rotor syndrome is characterized by mild conjugated and unconjugated hyperbilirubinemia that usually begins shortly after birth or in childhood. Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation.
Cholestasis-edema syndrome, Norwegian type
MedGen UID:
78658
Concept ID:
C0268314
Disease or Syndrome
Cholestasis-lymphedema syndrome is a rare genetic disorder characterized by neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and severe chronic lymphedema which mainly affects the lower limbs. Patients often present with fat malabsorption leading to failure to thrive, fat soluble vitamin deficiency with bleeding, rickets, and neuropathy. In 25% of cases, cirrhosis occurs during childhood or later in life.
Hyperbilirubinemia - conjugated - type III
MedGen UID:
98323
Concept ID:
C0400964
Disease or Syndrome
Sialic acid storage disease, severe infantile type
MedGen UID:
203367
Concept ID:
C1096902
Disease or Syndrome
Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.
Arthrogryposis, renal dysfunction, and cholestasis 1
MedGen UID:
347219
Concept ID:
C1859722
Disease or Syndrome
Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene.
Benign recurrent intrahepatic cholestasis type 2
MedGen UID:
435857
Concept ID:
C2608083
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.
Arthrogryposis, renal dysfunction, and cholestasis 2
MedGen UID:
462022
Concept ID:
C3150672
Disease or Syndrome
Arthrogryposis, renal dysfunction, and cholestasis-2 (ARCS2) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells (Qiu et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of ARCS, see ARCS1 (208085).
Progressive familial intrahepatic cholestasis type 2
MedGen UID:
483742
Concept ID:
C3489789
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.
Sideroblastic anemia 3
MedGen UID:
895975
Concept ID:
C4225155
Disease or Syndrome
Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit (summary by Liu et al., 2014). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).
Cholestasis, progressive familial intrahepatic, 5
MedGen UID:
934714
Concept ID:
C4310747
Disease or Syndrome
Progressive familial intrahepatic cholestasis-5 (PFIC5) is an autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy (summary by Gomez-Ospina et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600).
Asphyxiating thoracic dystrophy 1
MedGen UID:
1648057
Concept ID:
C4551856
Congenital Abnormality
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). Genetic Heterogeneity of Asphyxiating Thoracic Dysplasia SRTD1 has been mapped to chromosome 15q13. See also SRTD2 (611263), caused by mutation in the IFT80 gene (611177); SRTD3 (613091), caused by mutation in the DYNC2H1 gene (603297); SRTD4 (613819), caused by mutation in the TTC21B gene (612014); SRTD5 (614376), caused by mutation in the WDR19 gene (608151); SRTD6 (263520), caused by mutation in the NEK1 gene (604588); SRTD7 (614091), caused by mutation in the WDR35 gene (613602); SRTD8 (615503), caused by mutation in the WDR60 gene (615462); SRTD9 (266920), caused by mutation in the IFT140 gene (614620); SRTD10 (615630), caused by mutation in the IFT172 gene (607386); SRTD11 (615633), caused by mutation in the WDR34 gene (613363); SRTD13 (616300), caused by mutation in the CEP120 gene (613446); SRTD14 (616546), caused by mutation in the KIAA0586 gene (610178); SRTD15 (617088), caused by mutation in the DYNC2LI1 gene (617083); SRTD16 (617102), caused by mutation in the IFT52 gene (617094); SRTD17 (617405), caused by mutation in the TCTEX1D2 gene (617353); SRTD18 (617866), caused by mutation in the IFT43 gene (614068); SRTD19 (617895), caused by mutation in the IFT81 gene (605489); SRTD20 (617925), caused by mutation in the INTU gene (610621); and SRTD21 (619479), caused by mutation in the KIAA0753 gene (617112). See also SRTD12 (Beemer-Langer syndrome; 269860).
Progressive familial intrahepatic cholestasis type 1
MedGen UID:
1645830
Concept ID:
C4551898
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.
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.
Bile acid conjugation defect 1
MedGen UID:
1780260
Concept ID:
C5543203
Disease or Syndrome
Bile acid conjugation defect-1 (BACD1) is an autosomal recessive metabolic disorder characterized by onset of symptoms, including jaundice and failure to thrive, in early infancy. The clinical features of the disorder result from impaired absorption of fat-soluble vitamins. Vitamin D deficiency causes rickets with variable growth deficiency, and vitamin K deficiency causes a coagulopathy with decreased production of vitamin K-dependent clotting factors. More variable features may include pruritis, anemia, hepatomegaly, and bile duct proliferation on liver biopsy. Laboratory studies show abnormally increased levels of unconjugated bile acids (summary by Setchell et al., 2013). See also familial hypercholanemia (FHCA; 607748), in which patients have increased serum bile levels of conjugated bile acids.
Cholestasis, progressive familial intrahepatic, 6
MedGen UID:
1794175
Concept ID:
C5561965
Disease or Syndrome
Progressive familial intrahepatic cholestasis-6 (PFIC6) is an autosomal recessive disorder characterized by elevated liver transaminases, cholestasis, and congenital diarrhea (Gao et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600).
Biliary, renal, neurologic, and skeletal syndrome
MedGen UID:
1794200
Concept ID:
C5561990
Disease or Syndrome
Biliary, renal, neurologic, and skeletal syndrome (BRENS) is an autosomal recessive complex ciliopathy with multisystemic manifestations. The most common presentation is severe neonatal cholestasis that progresses to liver fibrosis and cirrhosis. Most patients have additional clinical features suggestive of a ciliopathy, including postaxial polydactyly, hydrocephalus, retinal abnormalities, and situs inversus. Additional features of the syndrome may include congenital cardiac defects, echogenic kidneys with renal failure, ocular abnormalities, joint hyperextensibility, and dysmorphic facial features. Some patients have global developmental delay. Brain imaging typically shows dilated ventricles, hypomyelination, and white matter abnormalities, although some patients have been described with abnormal pituitary development (summary by Shaheen et al., 2020 and David et al., 2020).
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).
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).

Recent clinical studies

Etiology

Parra DA, Peters SE, Kohli R, Chamlati R, Connolly BL, Wolinska JM, Ng VL, Temple MJ, John PR, Kamath BM, Ling SC, Fecteau A, Amirabadi A, Amaral JG
BMC Pediatr 2023 Jan 14;23(1):22. doi: 10.1186/s12887-022-03816-y. PMID: 36639762Free PMC Article
Edwards M, Falzone N, Harrington J
Eur J Pediatr 2021 May;180(5):1653-1657. Epub 2021 Jan 19 doi: 10.1007/s00431-021-03944-0. PMID: 33469712
Hashmi SK, Navai SA, Chambers TM, Scheurer ME, Hicks MJ, Rau RE, Gramatges MM
Pediatr Blood Cancer 2020 Feb;67(2):e28063. Epub 2019 Nov 17 doi: 10.1002/pbc.28063. PMID: 31736183Free PMC Article
Barseghyan K, Ramanathan R, Chavez T, Harlan S, Lin CH, Mitsinikos T, McLean C
J Matern Fetal Neonatal Med 2018 Dec;31(24):3249-3254. Epub 2017 Aug 31 doi: 10.1080/14767058.2017.1368479. PMID: 28818034
İpek MŞ, Aydın M, Zencıroğlu A, Gökçe S, Okumuş N, Gülaldı NC
Turk J Gastroenterol 2013;24(5):406-14. doi: 10.4318/tjg.2013.0553. PMID: 24557964

Diagnosis

Parra DA, Peters SE, Kohli R, Chamlati R, Connolly BL, Wolinska JM, Ng VL, Temple MJ, John PR, Kamath BM, Ling SC, Fecteau A, Amirabadi A, Amaral JG
BMC Pediatr 2023 Jan 14;23(1):22. doi: 10.1186/s12887-022-03816-y. PMID: 36639762Free PMC Article
Morais MB, Machado MV
United European Gastroenterol J 2022 Sep;10(7):745-753. Epub 2022 Jul 20 doi: 10.1002/ueg2.12279. PMID: 35860851Free PMC Article
Edwards M, Falzone N, Harrington J
Eur J Pediatr 2021 May;180(5):1653-1657. Epub 2021 Jan 19 doi: 10.1007/s00431-021-03944-0. PMID: 33469712
Barseghyan K, Ramanathan R, Chavez T, Harlan S, Lin CH, Mitsinikos T, McLean C
J Matern Fetal Neonatal Med 2018 Dec;31(24):3249-3254. Epub 2017 Aug 31 doi: 10.1080/14767058.2017.1368479. PMID: 28818034
Gottesman LE, Del Vecchio MT, Aronoff SC
BMC Pediatr 2015 Nov 20;15:192. doi: 10.1186/s12887-015-0506-5. PMID: 26589959Free PMC Article

Therapy

Stovicek J, Hlava S, Keil R, Drabek J, Lochmannova J, Koptová P, Wasserbauer M, Frybova B, Snajdauf J, Kotalova R, Rygl M
Can J Gastroenterol Hepatol 2021;2021:9969825. Epub 2021 Jun 24 doi: 10.1155/2021/9969825. PMID: 34258256Free PMC Article
Hashmi SK, Navai SA, Chambers TM, Scheurer ME, Hicks MJ, Rau RE, Gramatges MM
Pediatr Blood Cancer 2020 Feb;67(2):e28063. Epub 2019 Nov 17 doi: 10.1002/pbc.28063. PMID: 31736183Free PMC Article
Piwowarczyk P, Kutnik P, Potręć-Studzińska B, Sysiak-Sławecka J, Rypulak E, Borys M, Czczuwar M
Int J Artif Organs 2019 May;42(5):263-268. Epub 2019 Mar 28 doi: 10.1177/0391398819834012. PMID: 30919732
Barseghyan K, Ramanathan R, Chavez T, Harlan S, Lin CH, Mitsinikos T, McLean C
J Matern Fetal Neonatal Med 2018 Dec;31(24):3249-3254. Epub 2017 Aug 31 doi: 10.1080/14767058.2017.1368479. PMID: 28818034
Klein CJ, Revenis M, Kusenda C, Scavo L
J Am Diet Assoc 2010 Nov;110(11):1684-95. doi: 10.1016/j.jada.2010.08.012. PMID: 21034882

Prognosis

Stovicek J, Hlava S, Keil R, Drabek J, Lochmannova J, Koptová P, Wasserbauer M, Frybova B, Snajdauf J, Kotalova R, Rygl M
Can J Gastroenterol Hepatol 2021;2021:9969825. Epub 2021 Jun 24 doi: 10.1155/2021/9969825. PMID: 34258256Free PMC Article
Hashmi SK, Navai SA, Chambers TM, Scheurer ME, Hicks MJ, Rau RE, Gramatges MM
Pediatr Blood Cancer 2020 Feb;67(2):e28063. Epub 2019 Nov 17 doi: 10.1002/pbc.28063. PMID: 31736183Free PMC Article
Mantadakis E, Chatzimichael E, Kontekaki E, Panopoulou M, Martinis G, Tsalkidis A
J Pediatr Hematol Oncol 2019 May;41(4):324-327. doi: 10.1097/MPH.0000000000001184. PMID: 29683945
Barseghyan K, Ramanathan R, Chavez T, Harlan S, Lin CH, Mitsinikos T, McLean C
J Matern Fetal Neonatal Med 2018 Dec;31(24):3249-3254. Epub 2017 Aug 31 doi: 10.1080/14767058.2017.1368479. PMID: 28818034
İpek MŞ, Aydın M, Zencıroğlu A, Gökçe S, Okumuş N, Gülaldı NC
Turk J Gastroenterol 2013;24(5):406-14. doi: 10.4318/tjg.2013.0553. PMID: 24557964

Clinical prediction guides

Stovicek J, Hlava S, Keil R, Drabek J, Lochmannova J, Koptová P, Wasserbauer M, Frybova B, Snajdauf J, Kotalova R, Rygl M
Can J Gastroenterol Hepatol 2021;2021:9969825. Epub 2021 Jun 24 doi: 10.1155/2021/9969825. PMID: 34258256Free PMC Article
Hashmi SK, Navai SA, Chambers TM, Scheurer ME, Hicks MJ, Rau RE, Gramatges MM
Pediatr Blood Cancer 2020 Feb;67(2):e28063. Epub 2019 Nov 17 doi: 10.1002/pbc.28063. PMID: 31736183Free PMC Article
Piwowarczyk P, Kutnik P, Potręć-Studzińska B, Sysiak-Sławecka J, Rypulak E, Borys M, Czczuwar M
Int J Artif Organs 2019 May;42(5):263-268. Epub 2019 Mar 28 doi: 10.1177/0391398819834012. PMID: 30919732
Barseghyan K, Ramanathan R, Chavez T, Harlan S, Lin CH, Mitsinikos T, McLean C
J Matern Fetal Neonatal Med 2018 Dec;31(24):3249-3254. Epub 2017 Aug 31 doi: 10.1080/14767058.2017.1368479. PMID: 28818034
İpek MŞ, Aydın M, Zencıroğlu A, Gökçe S, Okumuş N, Gülaldı NC
Turk J Gastroenterol 2013;24(5):406-14. doi: 10.4318/tjg.2013.0553. PMID: 24557964

Recent systematic reviews

Gottesman LE, Del Vecchio MT, Aronoff SC
BMC Pediatr 2015 Nov 20;15:192. doi: 10.1186/s12887-015-0506-5. PMID: 26589959Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...
    Support Center