ABSTRACT Gilbert syndrome is a common autosomal dominant hereditary condition with incomplete penetrance and characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis. In patients with Gilbert syndrome, uridine diphosphate-glucuronyl transferase activity is reduced to 30% of the normal, resulting in indirect hyperbilirubinemia. In its typical form, hyperbilirubinemia is first noticed as intermittent mild jaundice in adolescence. However, Gilbert syndrome in combination with other prevailing conditions such as breast feeding, G-6-PD deficiency, thalassemia, spherocytosis, or cystic fibrosis may potentiate severe hyperbilirubinemia and/or cholelithiasis. It may also reduce plasma oxidation, and it may also affect drug metabolism. Although in general the diagnosis of the syndrome is one of exclusion, molecular genetic tests can now be performed when there is a diagnostic problem. The most common genotype of Gilbert syndrome is the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter designated UGT1A1*28. No specific management is necessary as Gilbert syndrome is a benign condition. CONCLUSION: Gilbert genotype should be kept in the clinician's mind, at least as a contributor factor, in cases with unexplained indirect hyperbilirubinemia.
- JAMA The Journal of the American Medical Association 02/2015; 313(5):516-7. DOI:10.1001/jama.2014.12835 · 30.39 Impact Factor
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ABSTRACT: Chronic lymphocytic leukemia (CLL) has been recently attributed to a combination of genetic predisposition and exposure to environmental factors. UDP-glucuronosyltransferase (UGT)1A1*28 is an inborn polymorphism that results in significant downregulation of uridine diphosphate glucuronyltransferase 1-1 (UGT1A1) activity, one of the most critical metabolizing enzymes involved in the detoxification of toxic substances, some of which contribute to CLL pathogenesis. Here, for the first time, we investigated the putative impact of UGT1A1*28 on CLL incidence and on the formation of the most common chromosomal abnormalities of CLL. UGT1A1*28 was investigated in 109 CLL patients and 108 healthy controls, and was associated with karyotypic and fluorescence in situ hybridization (FISH) results. A significant high frequency of the mutant genotype was observed in patients carrying abnormal FISH patterns, especially del(11q) and +12, which are CLL-specific abnormalities. We also observed a significant association between UGT1A1*28 and the intermediate to unfavorable cytogenetic CLL risk groups. No difference, though, was observed in genotypes between patients and controls. Therefore, we could suggest that UGT-deficient individuals may be at a greater risk for developing CLL-specific abnormalities. Our study might serve as a starting point to consider UGT1A1*28 polymorphism as one of the possible predisposing factors of CLL pathogenesis. © 2014 S. Karger AG, Basel.Acta Haematologica 01/2014; 132(1):59-67. DOI:10.1159/000355714 · 0.99 Impact Factor
Article: Hereditary Hyperbilirubinemias[Show abstract] [Hide abstract]
ABSTRACT: Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, CriglerNajjar, Dubin-Johnson and Rotor, among which the first two are characterized by unconjugated and the second two by conjugated hyperbilirubinemia. Gilbert syndrome occurs in 2%-10% of general population, while others are rare. Except for Crigler-Najjar syndrome, hereditary hyperbilirubinemias belong to benign disorders and thus no treatment is required.Srpski arhiv za celokupno lekarstvo 03/2014; 142(3-4):257-60. DOI:10.2298/SARH1404257R · 0.17 Impact Factor