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Best Practice & Research. Clinical... Oct 2010Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies. Inherited non-haemolytichyperbilirubinemic... (Review)
Review
Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies. Inherited non-haemolytichyperbilirubinemic conditions include Dubin-Johnson, Rotor, and Gilbert-Meulengracht syndromes, which are important differential diagnoses indicating benign disease that require no immediate treatment. Dubin-Johnson and Rotor syndromes are rare, exhibit mixed direct and indirect hyperbilirubinemia as well as typical profiles or urinary coproporphyrin excretion. Gilbert-Meulengracht disease leads to unconjugated hyperbilirubinemia because of impaired glucuronidation activity, and is part of a spectrum of genetic variants also encompassing fatal Crigler-Najjar syndrome. Gilbert-Meulengracht syndrome can be diagnosed by clinical presentation, biochemistry and genotyping, and carries significance regarding the disposition towards drug-associated toxicity. In addition, the precise diagnosis of these inherited hyperbilirubinemic syndromes avoids unnecessary invasive procedures for suspected more severe hepatobiliary disease.
Topics: Animals; Antineoplastic Agents, Phytogenic; Bilirubin; Camptothecin; Crigler-Najjar Syndrome; Diagnosis, Differential; Genetic Predisposition to Disease; Genetic Variation; Gilbert Disease; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Hereditary; Irinotecan; Jaundice, Chronic Idiopathic; Neoplasms
PubMed: 20955959
DOI: 10.1016/j.bpg.2010.07.007 -
Pediatric Research Mar 2016Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be... (Review)
Review
Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.
Topics: Animals; Bile; Bilirubin; Crigler-Najjar Syndrome; Gilbert Disease; Glucuronic Acid; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Hereditary; Hyperbilirubinemia, Neonatal; Jaundice, Chronic Idiopathic; Liver
PubMed: 26595536
DOI: 10.1038/pr.2015.247 -
Srpski Arhiv Za Celokupno Lekarstvo 2014Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, CriglerNajjar, Dubin-Johnson and Rotor, among which the first two are... (Review)
Review
Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, CriglerNajjar, Dubin-Johnson and Rotor, among which the first two are characterized by unconjugated and the second two by conjugated hyperbilirubinemia. Gilbert syndrome occurs in 2%-10% of general population, while others are rare. Except for Crigler-Najjar syndrome, hereditary hyperbilirubinemias belong to benign disorders and thus no treatment is required.
Topics: Bilirubin; Crigler-Najjar Syndrome; Gilbert Disease; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary
PubMed: 24839786
DOI: 10.2298/sarh1404257r -
Lancet (London, England) Oct 1978
Topics: Crigler-Najjar Syndrome; Diagnosis, Differential; Gilbert Disease; Humans; Hyperbilirubinemia, Hereditary; Infant, Newborn; Jaundice, Chronic Idiopathic; Jaundice, Neonatal
PubMed: 81933
DOI: No ID Found -
Schweizerische Rundschau Fur Medizin... Feb 1992A 22-year-old woman had icteric sclerae since childhood. Five years ago of Gilbert-Meulengracht's disease was diagnosed (hyperbilirubinemia, normal other liver...
A 22-year-old woman had icteric sclerae since childhood. Five years ago of Gilbert-Meulengracht's disease was diagnosed (hyperbilirubinemia, normal other liver laboratory parameters, no evidence of hemolysis). The patient was admitted for re-evaluation. Apart from jaundice of the sclerae no other clinical symptoms were found. Analysis of urine revealed bilirubin and an increased urobilinogen. Serum bilirubin was also elevated. The differentiation of the bilirubin gave evidence of an increase of the direct (conjugated) bilirubin portion. Additional investigations (total coproporphyrin in the urine, isomer I and isomer III coproporphyrin excretion and bromsulphalein test) suggested Rotor's syndrome. Further examinations (oral cholecystography, liver biopsy) were not added because of relative invasiveness, lack of clinical consequences and opposition of the patient. Nevertheless the diagnosis of a Rotor's syndrome is highly probable.
Topics: Adult; Bilirubin; Diagnosis, Differential; Female; Humans; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Syndrome; Urobilinogen
PubMed: 1539119
DOI: No ID Found -
Deutsche Medizinische Wochenschrift... Sep 1966
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Digestive and Liver Disease : Official... Jun 2009Hyperbilirubinemia is a common laboratory finding in clinical practice, being found in several haematological and liver diseases as well as in familial conditions (5-10%... (Review)
Review
Hyperbilirubinemia is a common laboratory finding in clinical practice, being found in several haematological and liver diseases as well as in familial conditions (5-10% in Western countries). Although most of the familial forms of hyperbilirubinemia are classically viewed as benign conditions, they have gained an increased interest in the last few years since recent data have indicated that subjects with an impaired bilirubin metabolism may have an increased susceptibility to drug toxicity. The authors briefly review the main steps of bilirubin metabolism, with a special emphasis on the emerging concepts on the molecular mechanisms of regulation by nuclear receptors (NRs) and genetic factors. Then the different forms of isolated hyperbilirubinemia occurring in both adults and paediatrics are systematically analysed, and a new categorisation is also proposed in light of the recent advances in bilirubin research. Finally, a diagnostic algorithm is discussed, along with a correct approach to its management, in order to avoid unnecessary medical investigations.
Topics: Adult; Algorithms; Bilirubin; Child; Child, Preschool; Diagnosis, Differential; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Young Adult
PubMed: 19196555
DOI: 10.1016/j.dld.2008.11.006 -
Seminars in Liver Disease Nov 1994
Topics: Animals; Crigler-Najjar Syndrome; Gilbert Disease; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Jaundice
PubMed: 7855630
DOI: 10.1055/s-2007-1007327 -
Journal of Biomedical Science 2005In bilirubin metabolism, increased destruction of erythrocytes, defect in the function of organic anion transporter polypeptide 2 (OATP2) or UDP-glucuronosyltransferase... (Review)
Review
In bilirubin metabolism, increased destruction of erythrocytes, defect in the function of organic anion transporter polypeptide 2 (OATP2) or UDP-glucuronosyltransferase 1A1 (UGT1A1) may result in unconjugated hyperbilirubinemia. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is known to be associated with the development of neonatal hyperbilirubinemia, it was observed that in neonates severe hyperbilirubinemia caused by G6PD deficiency, without associated polymorphisms in the UGT1A1 or the OATP2 gene, was preventable. Variations at the nucleotide (nt) 388 of OATP2 gene and nt-211 of UGT1A1 gene, were found to be a risk factor for severe hyperbilirubinemia amongst Taiwanese neonates, respectively. G6PD deficiency, variations at nts 388 and 521 of OATP2 gene, and variations at nt-211 and in the promoter area of UGT1A1 gene were reported to be the risk factors for the occurrence of mild hyperbilirubinemia amongst Taiwanese adults. The status of the haplotypes of G6PD, OATP2, and UGT1A1 genes affected the odds ratio and the bilirubin levels in the hyperbilirubinemic subjects. Moreover, carriage of the variant-211 UGT1A1 allele, as well as UGT1A7*3 allele, was demonstrated to represent a risk factor for the development of, and a determinant for, metastases associated with Taiwanese colorectal-cancer patients. Further investigation is warranted to evaluate this phenomenon.
Topics: Adult; Bilirubin; Crigler-Najjar Syndrome; Genetic Variation; Gilbert Disease; Glucosephosphate Dehydrogenase Deficiency; Glucuronosyltransferase; Haplotypes; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Liver-Specific Organic Anion Transporter 1; Mutation; Neoplasms; Risk Factors; Taiwan
PubMed: 15965581
DOI: 10.1007/s11373-005-3863-5 -
United European Gastroenterology Journal Sep 2022Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated... (Review)
Review
Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. Hyperbilirubinemia is an important clinical sign that needs to be investigated under a stepwise evaluation. Inherited non-hemolytic conjugated hyperbilirubinemic conditions include Dubin-Johnson syndrome (caused by mutations affecting ABCC2 gene) and Rotor syndrome (caused by the simultaneous presence of mutations in SLCO1B1 and SLCO1B3 genes). Although classically viewed as benign conditions requiring no treatment, they lately gained an increased interest since recent studies suggested that mutations in the responsible genes leading to hyperbilirubinemia, as well as minor genetic variants, may result in an increased susceptibility to drug toxicity. This article provides a comprehensive review on the pathophysiology of Dubin-Johnson and Rotor syndromes, presenting the current knowledge concerning the molecular details and basis of these conditions.
Topics: Bilirubin; Heme; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Liver-Specific Organic Anion Transporter 1
PubMed: 35860851
DOI: 10.1002/ueg2.12279