Coexistence of Gilbert syndrome with hereditary haemolytic anaemias
- 1Department of Paediatrics, Haematology and Oncology, Medical University of Warsaw, Warsaw, Poland
- 2Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
- Correspondence to Professor Beata Burzynska, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawińskiego 5A, 02-106 Warsaw, Poland;
Contributors KR and BB conceived and designed the experiments. KR and AT performed the experiments. KR, AAS and BB analysed the data. AAS and MM undertook patient recruitment and clinical care. KR and BB wrote the paper.
- Accepted 14 February 2012
- Published Online First 3 May 2012
Background Gilbert syndrome is an inherited disease characterised by mild unconjugated hyperbilirubinaemia caused by mutations in UGT1A1 gene which lead to decreased activity of UDP-glucuronosyltransferase 1A1. The most frequent genetic defect is a homozygous TA dinucleotide insertion in the regulatory TATA box in the UGT1A1 gene promoter.
Methods and results 182 Polish healthy individuals and 256 patients with different types of hereditary haemolytic anaemias were examined for the A(TA)nTAA motif. PCR was performed using sense primer labelled by 6-Fam and capillary electrophoresis was carried out in an ABI 3730 DNA analyser. The frequency of the (TA)7/(TA)7 genotype in the control group was estimated at 18.13%, (TA)6/(TA)7 at 45.05% and (TA)6/(TA)6 at 36.26%. There was a statistically significant difference in the (TA)6/(TA)6 genotype distribution between healthy individuals and patients with glucose-6-phosphate dehydrogenase deficiency (p=0.041). Additionally, uncommon genotypes, (TA)5/(TA)6, (TA)5/(TA)7 and (TA)7/(TA)8 of the promoter polymorphism, were discovered.
Conclusion Genotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)nTAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important.
- Gilbert syndrome
- hereditary haemolytic anaemia
- unconjugated hyperbilirubinemia
- diagnostic screening
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics approval was provided by Ethical Committee of the Medical University of Warsaw, Poland.
Provenance and peer review Not commissioned; externally peer reviewed.