Gilbert Syndrome
Basics
Also known as Meulengracht disease
Description
A benign, inherited syndrome in which mild, intermittent unconjugated hyperbilirubinemia occurs in the absence of hemolysis or liver dysfunctionPediatric Considerations
- Rare for the disorder to be diagnosed before puberty
- May contribute to prolongation of neonatal jaundice, especially in breastfed infants or infants with other hemolytic disorders
Pregnancy Considerations
The relative fasting that may occur with morning sickness can elevate bilirubin level.
Epidemiology
- Predominant age: present from birth but most often presents in the 2nd or 3rd decade of life
- Predominant sex: male > female (2 to 7:1)
Prevalence
The reported prevalence of Gilbert syndrome (GS) is between 2% and 20% in different populations (with the highest prevalence in the Middle Eastern population), with most presentations during or after adolescence.
Etiology and Pathophysiology
Indirect hyperbilirubinemia in GS results from impaired hepatic bilirubin clearance (~30% of normal) due to decreased levels of the enzyme uridine diphosphoglucuronate-glucuronosyltransferase (UDPGT). Hepatic bilirubin conjugation (glucuronidation) is thus reduced, although this may not be the only defect.
Genetics
- Inherited defects within the promoter region of the gene that encodes the enzyme UDPGT yields reduced conjugation of bilirubin with glucuronic acid. In particular, patients with GS have a mutation in the UGT1A1 gene.
- Once considered as an autosomal dominant condition, GS is now thought to be inherited in an autosomal recessive manner.
Risk Factors
- Male gender
- Family history; particularly first-degree relatives
General Prevention
Avoidance of known triggers (dehydration, prolonged fasting, intense exercise)
Commonly Associated Conditions
GS is part of a spectrum of hereditary disorders that includes types I and II Crigler-Najjar syndrome. However, bilirubin levels in these cases will be >6 mg/dL. There is an associated increased risk of cholelithiasis in certain populations. A neonatal presentation may lead to prolonged jaundice.
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