Idiopathic Unconjugated Hyperbilirubinemia (Gilbert's Syndrome)

Powell, Lawrie W.; Hemingway, Elaine; Billing, Barbara H.; Sherlock, Sheila

doi:10.1056/nejm196711232772102

Cited by 155 publications

(74 citation statements)

References 22 publications

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“…Genetic studies indicate that Gilbert syndrome is inherited as an autosomal dominant trait and the sex difference in prevalence suggests the possibility of incomplete penetration of the affected gene in both males and females. The reported prevalence of Gilbert syndrome varies from 3% to 12% in various ethnic groups 5,[8][9][10] but has not been previously examined in Saudis. In this study of a Saudi population, the prevalence was 3.6% (16 out of 450).…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic Unconjugated Hyperbilirubinemia (Gilbert Syndrome) among Saudis in Jeddah

1995

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Section: Discussionmentioning

confidence: 99%

Asymptomatic Unconjugated Hyperbilirubinemia (Gilbert Syndrome) among Saudis in Jeddah

1995

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“…2,3,11,15,16 Although hemolysis was not assessed directly by 51 Cr-erythrocyte survival, 16,17 or CO production rate, 28,33 none of our subjects evidenced overt hemolysis on standard hematologic tests. In addition, none (except the CN patient) were exposed to xenobiotics that decrease plasma bilirubin levels by inducing the activity of UGT1A1 or organic anion uptake.…”

Section: Discussionmentioning

confidence: 77%

“…Gilbert's Syndrome (GS) is an inherited form of mild, chronic, unconjugated hyperbilirubinemia, [1][2][3] which is associated with an extra TA in the promoter region of both alleles for bilirubin UDP-glucuronosyltransferase 1 (UGT1A1). [4][5][6][7][8] The resultant 65% decrease in transcription of the (TA) 7 TAA mutant alleles explains the impaired conjugation of bilirubin found in all GS patients.…”

mentioning

confidence: 99%

Hepatic uptake of organic anions affects the plasma bilirubin level in subjects with Gilbert's syndrome mutations in UGT1A1

Persico¹

2001

Hepatology

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Although in Gilbert's syndrome (GS), bilirubin glucuronidation is impaired due to an extra TA in the TATA box of the promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 (UGT1A1), many GS homozygotes lack unconjugated hyperbilirubinemia. Accordingly, an additional defect in bilirubin transport might be required for phenotypic expression. Plasma bilirubin and the early fractional hepatic uptake rate (BSP K 1 ) of a low dose of tetrabromosulfophthalein (0.59 mol/kg) were determined in (1) 15 unrelated patients with unconjugated hyperbilirubinemia plus 12 random controls; (2) 4 unrelated GS probands and 15 of their first-degree relatives; (3) 7 unrelated patients with hemolysis due to ␤-Thalassemia minor. Subjects were classified by DNA sequencing of the promoter region of both UGT1A1 alleles. In group 1, GS homozygotes showed a highly significant negative linear correlation between plasma bilirubin levels and BSP K 1 . BSP K 1 values overlapped considerably between GS and normal subjects, whereas, in group 2, they were clustered within, and sharply segregated among, families. Patients with hemolysis, despite elevated plasma bilirubin levels, had mean BSP K 1 values similar to the normal subjects. Within each GS subgroup with defined UGT1A1 mutations, the plasma bilirubin level is in part determined by the organic anion uptake rate, assessed by early plasma disappearance of low-dose BSP. The lower BSP uptake in GS is not secondary to the hyperbilirubinemia, but probably caused by (an) independent, genetically determined defect ( Gilbert's Syndrome (GS) is an inherited form of mild, chronic, unconjugated hyperbilirubinemia, 1-3 which is associated with an extra TA in the promoter region of both alleles for bilirubin UDP-glucuronosyltransferase 1 (UGT1A1). [4][5][6][7][8] The resultant 65% decrease in transcription of the (TA) 7 TAA mutant alleles explains the impaired conjugation of bilirubin found in all GS patients. 9,10 The abnormal (TA) 7 TAA allele has a reported prevalence of 34% to 40% in white adults 4,5 and Sephardic Jewish neonates. 11 Thus, 12% to 16% should be and are homozygous for this abnormality, 4-8 yet only 3% to 9% of such populations, or less than half the expected proportion of homozygotes, have an increased level of unconjugated bilirubin (UCB) in plasma. 7,8,[12][13][14] This suggests that additional steps in bilirubin metabolism and/or transport must be impaired for hyperbilirubinemia to be manifested in (TA) 7 TAA homozygotes with reduced expression of UGT1A1.Thus far, both increased bilirubin production (from hemolysis, 1-3,11,15,16 which may not be overt [16][17][18] ) and/or decreased hepatic uptake of UCB have been documented in many presumed GS subjects. Some also exhibit decreased plasma clearance of tetrabromosulfophthalein (BSP) 20-22 and other organic anions, 20,23,24 including several therapeutic agents, [24][25][26] which appear to share hepatic uptake mechanisms with UCB. 27 With BSP, impaired uptake may be unmasked in GS patients if the administered dose is reduced ...

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“…Das GilbertMeulengracht-Syndrom wird generell als eine autosomal rezessiv vererbte Erkrankung angesehen (Chowdhury et al 2001). Aber auch Fälle von heterozygoten und zusammengesetzt heterozygoten Merkmalsträgern und dominante Erbgänge wurden beschrieben (Foulk et al 1959, Powell et al 1967, Sleisenger et al 1967. Mutationen, die als Auslöser für das Gilbert-Meulengracht-Syndrom beschrieben wurden, betreffen in der Regel die sogenannte "TATA Box" (Bosma et al 1995), eine regulative Sequenz innerhalb des Promotors von UGT1A1 und verändern somit die Expressionshöhe der mRNA.…”

Section: Diskussionunclassified

“…Allerdings können auch Mutationen außerhalb des Promotors eines Gens Auswirkungen auf die Expressionshöhe haben. Für das Crigler-Najjar-Syndrom des Menschen sind vor allem rezessive Vererbungsmuster bekannt (Chowdhury et al 2001), aber auch dominante Erbgänge (Powell et al 1967) und rezessive Erbgänge mit Pseudodominanz (Guldutuna et al 1995). Mutationen, die beide Typen dieses Syndroms auslösen können, wurden in allen Exons von UGT1A1 beschrieben.…”

Section: Diskussionunclassified

Gilbert’s-, Arias’- or a still unknown syndrome - chronic icterus in a Norwegian Fjord Horse

Harland¹,

Mömke²,

Fink³

et al. 2010

PHK

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Idiopathic Unconjugated Hyperbilirubinemia (Gilbert's Syndrome)

Cited by 155 publications

References 22 publications

Asymptomatic Unconjugated Hyperbilirubinemia (Gilbert Syndrome) among Saudis in Jeddah

Asymptomatic Unconjugated Hyperbilirubinemia (Gilbert Syndrome) among Saudis in Jeddah

Hepatic uptake of organic anions affects the plasma bilirubin level in subjects with Gilbert's syndrome mutations in UGT1A1

Gilbert’s-, Arias’- or a still unknown syndrome - chronic icterus in a Norwegian Fjord Horse

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