In April 2016, a 28-year-old man (S.V.) in Ribeirao Preto, southeastern Brazil, with a history of Gilbert syndrome
sought care for a sudden high fever, severe 1-sided headache, vomiting, intense photophobia, stiff neck, and confusion.
(GS, MIM #143500) is characterized by fluctuating mild, unconjugated hyperbilirubinemia <85 [micro]mol/L and is caused by mutations in the bilirubin uridine diphosphate (UDP)-glucuronosyltransferase gene ( UGT1A1 ).[sup] Dubin-Johnson syndrome (DJS, MIM #237500) is characterized by fluctuating mild, predominantly conjugated hyperbilirubinemia and is caused by mutations in the ATP-binding cassette subfamily C member 2 gene ( ABCC2 ).[sup] This report described the unusual features encountered in a Chinese family that was genetically confirmed to have both DJS and GS.
This pathological mechanism underlies Gilbert syndrome
, in which an increase in indirect bilirubin levels enhance cholesterol excretion and decrease its production, thereby disrupting lipid balance (26).
Similarly, the National Comprehensive Cancer Network guidelines version 2.2016 states that irinotecan should be used with caution and at a decreased dose in patients with Gilbert syndrome
. Nevertheless, routine testing of UGT SNPs is not recommended, and dose modifications according to genotyping are not a standard practice .
Vitek, "Gilbert syndrome
, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin," Atherosclerosis, vol.
Genetic defects in the human UGT1A1 gene are associated with unconjugated hyperbilirubinemia, which can be either asymptomatic as in individuals with Gilbert syndrome
 or severe as in the case of Crigler-Najjar syndrome types I and II , depending on the remaining UGT1A1 activity.
Hyperbilirubinemia, augmentation of endothelial function and decrease in oxidative stress in gilbert syndrome
. Circulation 2012; 126: 598-603.
In April of 1995, he had an acute myocardial infarction and was also diagnosed with hepatitis B and Gilbert syndrome
. His daily life had become more physically uncomfortable and was exacerbated by painful hemorrhoids.
A 61 year old male with a history of coronary artery disease, hyperlipidemia, Gilbert syndrome
, and hypothyroidism had routine laboratory studies which revealed coagulation abnormalities.
Rare mutations in UGT1A1 produce the unconjugated hyperbilirubinemias--Crigler-Najjar syndromes I and II (OMIM 218800, 606785)--with absent and severely reduced enzyme activity, respectively (4-6).In contrast, Gilbert syndrome
(OMIM 145300), a mild inherited form of unconjugated hyperbilirubinemia that occurs in 15% of the population, is usually not treated or diagnosed because there are usually no clinical symptoms (7, 8); however, Gilbert syndrome
increases the risk of drug toxicity during cancer chemotherapy with irinotecan (Camptosar[R]; Pfizer) (9-11).
Both common and rare hereditary hepatic diseases, such as hereditary hemocliromatosis, Gilbert syndrome
(benign hyperbilirubinemia), Wilson's disease (a copper metabolism abnormality), and [alpha]1 - antitrypsin deficiency syndrome may be found in families.
Indeed, clinical trials have demonstrated that mild unconjugated hyperbilirubinemia (typically present in subjects with Gilbert syndrome
) is significantly associated with lower incidence of cardiovascular and pulmonary diseases, diabetes, metabolic syndrome, certain cancers, and even reduced overall mortality .