Gilbert Syndrome


Gilbert syndrome (GS) is considered the most common inherited disorder of bilirubin metabolism due to reduction of uridine diphosphate-glucuronyl transferase 1A1 activity. The hepatic bilirubin glucurodination activity is approximately 50% lower than normal. It is characterized by asymptomatic unconjugated hyperbilirubinemia in the absence of liver disease or hemolysis. GS is mild and benign condition inherited as autosomal recessive that affect being either homozygotes or compound heterozygotes (two different recessive alleles at a particular locus). It may be precipitated by dehydration, fasting, menstruation, overexertion or stress due to intercurrent febrile illness or even vigorous exercise. Other than experiencing jaundice patients are typically asymptomatic. GS usually manifests itself after puberty, affects 3-7% of the population with male predominance. Children may report vague abdominal discomfort, general fatigue and malaise without evident cause. Caloric restriction raises the serum unconjugated bilirubin lever twofold in affected patients with Gilbert syndrome. Fasting, caloric restriction and the intravenous nicotinic acid (niacin) provocative test has been used to diagnosed GS. The oral rifampin test induces cytochrome P-450 isoenzymes and competes for the excretory pathways in the liver at the cellular level causing an exaggerated elevation in unconjugated total serum bilirubin level in GS. Liver biopsy is not indicated and is usually normal. Genetic testing for the A(TA)7TAA variant and Gly71Arg mutation is diagnostic of Gilbert syndrome. GS can present in the newborn period if there is concurrent hemolytic disease such as ABO incompatibility, hereditary spherocytosis or G6PD deficiency. GS has been found to be a precipitating factor for idiopathic cholelithiasis in children. There is no specific treatment except to avoid fasting and severe stress. The prognosis overall is excellent.   

References:
1- Keren G, Mazilis A: Gilbert syndrome presenting in a young boy, confirmed by the rifampin test. Isr Med Assoc J. 9(8):626-7, 2007
2- Memon N, Weinberger BI, Hegyi T, Aleksunes LM: Inherited disorders of bilirubin clearance. Pediatr Res. 79(3):378-86, 2016
3- Lee JH, Moon KR: Coexistence of gilbert syndrome and hereditary spherocytosis in a child
presenting with extreme jaundice. Pediatr Gastroenterol Hepatol Nutr. 17(4):266-9, 2014
4- Kitsiou-Tzeli S, Kanavakis E, Tzetis M, Kavazarakis E, Galla A, Tsezou A: Gilbert's syndrome as a predisposing factor for idiopathic cholelithiasis in children. Haematologica. 88(10):1193-4, 2003
5- del Giudice EM, Perrotta S, Nobili B, Specchia C, d'Urzo G, Iolascon A: Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis. Blood. 94(7):2259-62, 1999
6- Karpathios T, Moustaki M, Yiallouros P, Sharifi F, Attilakos A, Papadopoulou A, Fretzayas A: Severe jaundice in two children with Kawasaki disease: a possible association with Gilbert syndrome.  J Korean Med Sci. 27(1):101-3, 2012


Home
Table
Index
Past
Review
Submit
Techniques
Editor
Handbook
Articles
Download
UPH
Journal Club
WWW
Meetings
Videos