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Gilbert syndrome(HBLRG)

MedGen UID:
4891
Concept ID:
C0017551
Disease or Syndrome
Synonyms: Gilbert Disease; Gilbert's syndrome; HYPERBILIRUBINEMIA I; HYPERBILIRUBINEMIA, ARIAS TYPE; HYPERBILIRUBINEMIA, GILBERT TYPE
SNOMED CT: Gilberts syndrome (27503000); Gilbert's syndrome (27503000); Gilbert-Lereboullet syndrome (27503000); Familial nonhemolytic bilirubinemia (27503000); Chronic intermittent juvenile jaundice (27503000); Constitutional hepatic dysfunction (27503000); Cholemia familiaris simplex (27503000); Familial nonhemolytic jaundice (27503000); Gilbert's disease (27503000); Hereditary nonhemolytic jaundice (27503000); Benign unconjugated bilirubinemia syndrome (27503000); Meulengracht syndrome (27503000); Low-grade chronic hyperbilirubinemia syndrome (27503000); Congenital familial cholemia (27503000); Gilbert syndrome (27503000)
 
Gene (location): UGT1A1 (2q37.1)
 
Monarch Initiative: MONDO:0007745
OMIM®: 143500
Orphanet: ORPHA357

Definition

The hereditary hyperbilirubinemias include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I (218800), and Crigler-Najjar syndrome type II (606785); and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300) (Wolkoff et al., 1983). Detailed studies show that patients with Gilbert syndrome have reduced activity of bilirubin glucuronosyltransferase (Bosma et al., 1995, Koiwai et al., 1995). Genetic Heterogeneity of Hyperbilirubinemia See also Crigler-Najjar syndrome type I (HBLRCN1; 218800), Crigler-Najjar syndrome type II (HBLRCN2; 606785), and transient familial neonatal hyperbilirubinemia (HBLRTFN; 237900), all caused by mutation in the UGT1A1 gene (191740) on chromosome 2q37; Dubin-Johnson syndrome (DJS, HBLRDJ; 237500), caused by mutation in the ABCC2 gene (601107) on chromosome 10q24; and Rotor syndrome (HBLRR; 237450), caused by digenic mutation in the SLCO1B1 (604843) and SLCOB3 (605495) genes, both on chromosome 12p. [from OMIM]

Additional description

From MedlinePlus Genetics
Gilbert syndrome is a relatively mild condition characterized by periods of elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin, which has an orange-yellow tint, is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Gilbert syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). In affected individuals, bilirubin levels fluctuate and very rarely increase to levels that cause jaundice, which is yellowing of the skin and whites of the eyes.

Gilbert syndrome is usually recognized in adolescence. If people with this condition have episodes of hyperbilirubinemia, these episodes are generally mild and typically occur when the body is under stress, for instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with Gilbert syndrome also experience abdominal discomfort or tiredness. However, approximately 30 percent of people with Gilbert syndrome have no signs or symptoms of the condition and are discovered only when routine blood tests reveal elevated unconjugated bilirubin levels.  https://medlineplus.gov/genetics/condition/gilbert-syndrome

Clinical features

From HPO
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Unconjugated hyperbilirubinemia
MedGen UID:
82786
Concept ID:
C0268306
Disease or Syndrome
An increased amount of unconjugated (indirect) bilurubin in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGilbert syndrome

Professional guidelines

PubMed

Kang LL, Liu ZL, Han QS, Chen YW, Liu LW, Xie XH, Luo JF, Ji YQ, Zhu GL, Ma YJ, Ji KM, Zhang HD
J Breath Res 2022 Mar 15;16(2) doi: 10.1088/1752-7163/ac57f9. PMID: 35196265
Schonfeld EA, Brown RS Jr
Clin Liver Dis 2017 Nov;21(4):673-686. Epub 2017 Jul 29 doi: 10.1016/j.cld.2017.06.001. PMID: 28987255
Petersen JP, Henriksen TB, Hollegaard MV, Vandborg PK, Hougaard DM, Thorlacius-Ussing O, Ebbesen F
Pediatrics 2014 Sep;134(3):510-5. Epub 2014 Aug 4 doi: 10.1542/peds.2014-0035. PMID: 25092941

Recent clinical studies

Etiology

Poynard T, Deckmyn O, Peta V, Sakka M, Lebray P, Moussalli J, Pais R, Housset C, Ratziu V, Pasmant E, Thabut D; FibroFrance Group
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 22 doi: 10.1097/HC9.0000000000000245. PMID: 37738404Free PMC Article
Zengin O, Sahiner ES, Inan O, Topcuoglu C, Turhan T, Altiparmak E, Yilmaz N, Ates I
Angiology 2022 Nov-Dec;73(10):920-926. Epub 2021 Dec 21 doi: 10.1177/00033197211057692. PMID: 34933608
Düzenli T, Maden Ö, Tanoğlu A, Kaplan M, Yazgan Y
Trends Psychiatry Psychother 2021 Apr-Jun;43(2):151-158. Epub 2021 Apr 2 doi: 10.47626/2237-6089-2020-0003. PMID: 33844900Free PMC Article
Vítek L
Physiol Res 2017 Apr 5;66(Suppl 1):S11-S20. doi: 10.33549/physiolres.933581. PMID: 28379026
Lambou-Gianoukos S, Heller SJ
Surg Clin North Am 2008 Dec;88(6):1175-94, vii. doi: 10.1016/j.suc.2008.07.009. PMID: 18992590

Diagnosis

Poynard T, Deckmyn O, Peta V, Sakka M, Lebray P, Moussalli J, Pais R, Housset C, Ratziu V, Pasmant E, Thabut D; FibroFrance Group
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 22 doi: 10.1097/HC9.0000000000000245. PMID: 37738404Free PMC Article
Vítek L
Physiol Res 2017 Apr 5;66(Suppl 1):S11-S20. doi: 10.33549/physiolres.933581. PMID: 28379026
Fargo MV, Grogan SP, Saguil A
Am Fam Physician 2017 Feb 1;95(3):164-168. PMID: 28145671
Memon N, Weinberger BI, Hegyi T, Aleksunes LM
Pediatr Res 2016 Mar;79(3):378-86. Epub 2015 Nov 23 doi: 10.1038/pr.2015.247. PMID: 26595536Free PMC Article
Fretzayas A, Moustaki M, Liapi O, Karpathios T
Eur J Pediatr 2012 Jan;171(1):11-5. Epub 2011 Dec 9 doi: 10.1007/s00431-011-1641-0. PMID: 22160004

Therapy

Goluch Z, Wierzbicka-Rucińska A, Książek E
Nutrients 2024 Jul 12;16(14) doi: 10.3390/nu16142247. PMID: 39064690Free PMC Article
Poynard T, Deckmyn O, Peta V, Sakka M, Lebray P, Moussalli J, Pais R, Housset C, Ratziu V, Pasmant E, Thabut D; FibroFrance Group
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 22 doi: 10.1097/HC9.0000000000000245. PMID: 37738404Free PMC Article
Düzenli T, Maden Ö, Tanoğlu A, Kaplan M, Yazgan Y
Trends Psychiatry Psychother 2021 Apr-Jun;43(2):151-158. Epub 2021 Apr 2 doi: 10.47626/2237-6089-2020-0003. PMID: 33844900Free PMC Article
Ha VH, Jupp J, Tsang RY
Pharmacotherapy 2017 Aug;37(8):956-972. Epub 2017 Jun 28 doi: 10.1002/phar.1946. PMID: 28494109
Vítek L
Physiol Res 2017 Apr 5;66(Suppl 1):S11-S20. doi: 10.33549/physiolres.933581. PMID: 28379026

Prognosis

Zengin O, Sahiner ES, Inan O, Topcuoglu C, Turhan T, Altiparmak E, Yilmaz N, Ates I
Angiology 2022 Nov-Dec;73(10):920-926. Epub 2021 Dec 21 doi: 10.1177/00033197211057692. PMID: 34933608
Krawczyk M, Miquel JF, Stokes CS, Zuniga S, Hampe J, Mittal B, Lammert F
Clin Res Hepatol Gastroenterol 2013 Apr;37(2):119-25. Epub 2013 Jan 20 doi: 10.1016/j.clinre.2012.09.002. PMID: 23340007
Paulík A, Grim J, Filip S
Acta Medica (Hradec Kralove) 2012;55(4):153-9. doi: 10.14712/18059694.2015.39. PMID: 23631285
Gil J, Sąsiadek MM
Biomark Med 2012 Apr;6(2):223-30. doi: 10.2217/bmm.12.4. PMID: 22448797
Maruo Y, Iwai M, Mori A, Sato H, Takeuchi Y
Curr Drug Metab 2005 Apr;6(2):91-9. doi: 10.2174/1389200053586064. PMID: 15853761

Clinical prediction guides

Zengin O, Sahiner ES, Inan O, Topcuoglu C, Turhan T, Altiparmak E, Yilmaz N, Ates I
Angiology 2022 Nov-Dec;73(10):920-926. Epub 2021 Dec 21 doi: 10.1177/00033197211057692. PMID: 34933608
Vítek L, Tiribelli C
J Hepatol 2021 Dec;75(6):1485-1490. Epub 2021 Jun 18 doi: 10.1016/j.jhep.2021.06.010. PMID: 34153399
Düzenli T, Maden Ö, Tanoğlu A, Kaplan M, Yazgan Y
Trends Psychiatry Psychother 2021 Apr-Jun;43(2):151-158. Epub 2021 Apr 2 doi: 10.47626/2237-6089-2020-0003. PMID: 33844900Free PMC Article
Vítek L
Physiol Res 2017 Apr 5;66(Suppl 1):S11-S20. doi: 10.33549/physiolres.933581. PMID: 28379026
Poynard T, Morra R, Ingiliz P, Imbert-Bismut F, Thabut D, Messous D, Munteanu M, Massard J, Benhamou Y, Ratziu V
Adv Clin Chem 2008;46:131-60. doi: 10.1016/s0065-2423(08)00404-6. PMID: 19004189

Recent systematic reviews

Goluch Z, Wierzbicka-Rucińska A, Książek E
Nutrients 2024 Jul 12;16(14) doi: 10.3390/nu16142247. PMID: 39064690Free PMC Article

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