History and exam

Key diagnostic factors

common

post-pubertal age

Rarely diagnosed before puberty. During puberty, there are alterations in sex steroids leading to higher levels of bilirubin.[16]

positive family history of GS

GS is most probably transmitted in an autosomal recessive pattern. However, inheritance patterns of GS have been difficult to ascertain. Data suggest an autosomal recessive pattern of inheritance, whereas earlier studies report a possible autosomal dominant transmission with incomplete penetrance.[12]

icterus (jaundice)

The hallmark of GS is icterus (jaundice), especially when under physical or psychological stress. The cause of hyperbilirubinaemia under stress is not entirely understood, though several hypotheses have been presented including increased haem turnover, increased enterohepatic uptake of unconjugated bilirubin, and altered hepatic uptake mechanisms.[23][24][25]

absence of hepatosplenomegaly

GS can be diagnosed if other disease processes can be excluded.

no stigmata of chronic liver disease

GS can be diagnosed if other disease processes can be excluded.

Risk factors

strong

post-pubertal age

GS is rarely diagnosed before puberty. During puberty, there are alterations in sex steroids leading to higher levels of bilirubin. Testosterone decreases the activity of uridine-diphosphoglucuronate glucuronosyltransferase (UDPGT), and female sex hormones exert the opposite effect, explaining the sex ratio in GS and the post-pubertal diagnosis.[16]

weak

family history of GS

GS is most likely inherited in an autosomal recessive manner; therefore, first-degree family members are at risk. However, inheritance patterns of GS have been difficult to ascertain. Data suggest an autosomal recessive pattern of inheritance, whereas earlier studies report a possible autosomal dominant transmission with incomplete penetrance.[12]

type 1 diabetes mellitus

GS is more frequent in patients with type 1 diabetes, with a 3-fold higher occurrence than in a healthy control group.[5]

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