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Cited by 138Neonatal Health and BiochemistryHeme Oxygenase-1 and Carbon MonoxidePediatric Hepatobiliary Diseases and Treatments

Diagnostic criteria and contributors to Gilbert’s syndrome

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Wagner, Karl-Heinz, Shiels, Ryan G., Lang, Claudia Anna, Seyed Khoei, Nazlisadat, Bulmer, Andrew C.·2018·Critical Reviews in Clinical Laboratory Sciences
DOI 10.1080/10408363.2018.1428526
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Abstract

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Assessment of bilirubin concentrations is typically conducted as part of routine liver function testing. Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts, however, may indicate the presence of Gilbert's syndrome (GS), a benign condition that is present in ∼5-10% of the population. In this case, mildly elevated unconjugated bilirubin in GS is strongly associated with "reduced" prevalence of chronic diseases, particularly cardiovascular diseases (CVD) and type 2 diabetes mellitus (and associated risk factors), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic by-product of heme catabolism and emphasize the importance of understanding its potential beneficial physiologic and detrimental pathophysiologic effects, in order to appropriately consider bilirubin test results within the clinical laboratory setting. With this information, we hope to improve the understanding of disorders of bilirubin metabolism, emphasize the diagnostic importance of these conditions, and outline the potential impact GS may have on resistance to disease.

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  • Meulengracht-Gilbert Syndrome (MGS) is a benign genetic disorder present in approximately 10% of young men in Bavaria, and it affects bilirubin processing leading to elevated levels of unconjugated bilirubin in the blood.

    “Meulengracht-Gilbert Syndrome (MGS), a benign genetic disorder which is present in approximately 10% of young men in Bavaria and affects bilirubin processing leading to elevated levels of unconjugated bilirubin in the blood [14], [15], [16].”

    From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [16]

    The ‘Bilirubin biology—An evolutionary perspective’ section describes Gilbert-Meulengracht syndrome as benign, reports a 2–10% prevalence among people of Caucasian ethnicity, and links elevated unconjugated bilirubin to genetic changes affecting its processing. It does not give a prevalence specifically for young men in Bavaria, so the claim’s population-specific figure is not supported by this source. (LLM, conf=0.89)

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Research works printed but not linked: 9

  1. Blaschke TF, Berk PD, Scharschm BF, et al. New approach to the estimation of early-labeled peak syn- thesis in man. In: Berk PD, Berlin NI, editors. Chemistry and Physiology of Bile Pigments. Bethesda: National Institutes of Health; 1977. p. 539.
  2. Horsfall LJ, Nazareth I, Pereira SP, et al. Gilbert's syn- drome and the risk of death: a population-based cohort study. J Gastroenterol Hepatol. 2013;28: 1643-1647.
  3. Mendez L, Lagoa M, Quiroga T, et al. [Prevalence of Gilbert syndrome and its genetic determinants in Chile]. Rev Med Chil. 2013;141:1266-1274. Spanish.
  4. Sieg A, Arab L, Schlierf G, et al. [Prevalence of Gilbert's syndrome in Germany]. Dtsch Med Wochenschr. 1987;112:1206-1208. German.
  5. Gilbert A, Lereboullet P. La cholamae simple familiale [The simple hereditary cholestasis]. Sem Med. 1901;21:241-248. French.
  6. Wallner M, Bulmer AC, Moelzer C, et al. Haem catab- olism: a novel modulator of inflammation in Gilbert's syndrome. Eur J Clin Invest. 2014;43: 912-919.
  7. den Dunnen JT, Antonarakis SE. Mutation nomencla- ture extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000;15:7-12.
  8. Jendrassik L, Grof P. Photometric determination of bilirubin in urine. Biochem Zeitschrift. 1938;296: 71-79.
  9. van den Bergh AAH. Diazo test for bilirubin in blood. JAMA. 1921;77:235.

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Authors
Wagner, K.-H., Shiels, R. G., Lang, C. A., Seyed Khoei, N., & Bulmer, A. C.
Affiliations
  • University of Vienna (AT)
  • Griffith University (AU)
  • Department of Nutritional Sciences and Research Platform Active Ageing, University of Vienna, Vienna, Austria;
Corresponding author
  • Wagner, Karl-Heinz
  • Bulmer, Andrew C.
ORCID
Venue
Critical Reviews in Clinical Laboratory Sciences
Publisher
Informa UK Limited
Published
2018-02
Volume
55
Issue
2
Pages
129-139
ISSN
  • 1040-8363 (ISSN-L)
  • 1549-781X
DOI
10.1080/10408363.2018.1428526
OpenAlex
W2793982710
Cited by
138
References
98
Citations by year
2026: 12 · 2025: 11 · 2024: 18 · 2023: 26 · 2022: 23 · 2021: 20 · 2020: 19 · 2019: 5 · 2018: 3
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Critical Reviews in Clinical Laboratory Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Phaidra (Universität Wien) (submittedVersion, cc-by-nc-nd)
  • Griffith Research Online (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
Keywords
Gilbert syndrome, hyperbilirubinemia, unconjugated hyperbilirubinemia, conjugated hyperbilirubinemia, Crigler-Najjar syndrome, Rotor syndrome, Dubin-Johnson syndrome, cardiovascular disease, type 2 diabetes, mortality, heme degradation, disease resistance
MeSH terms
UGT1A1 Enzyme, Bilirubin, Gilbert Disease, Humans, Hyperbilirubinemia, Glucuronosyltransferase

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