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Hyperbilirubinemia in patient with β-thalassemia intermedia combined with Gilbert`s syndrome - case report

Tsvetan Popov, Polina Ivanova, Suzan Nuhova, Valeria Kaleva


Introduction: Patients with β-thalassemia major and intermedia show a marked variability of serum indirect bilirubin levels. This variability may be related to several causes: transfused red blood cell destruction rate, ineffective erythropoiesis, hemolysis, or bilirubin elimination capacity which de­pends partially on the bilirubin glucuronidation activity.

Materials and methods: A case report of a 9-year-old male, born in 2007, is discussed. The patient was admitted and treated in the Clinic of Pediatric Hematology and Oncology at St. Marina University Hospital of Varna, Bulgaria. The anamnesis reported a mild to severe microcystic hypochromic ane­mia, subicterus and splenomegaly 6 months after birth. Genetic tests proved compound heterozygous Intervening sequence (IVS) I-110/IVS I-6 state, typical for β-thalassemia. Upon physical examination in 2011, the patient presented with splenomegaly and persisting unconjugated hyperbilirubinemia.

Results: Considering the patient`s clinical profile and laboratory tests, with an emphasis on the dis­proportionate hyperbilirubinemia (120mmol/l), the possibility of a coherent genetic mutation was discussed. The genetic testing came back positive for homozygosity for (T [Thymine] A [Adenine])7 - uridine 5`-diphospho-glucuronosyltransferase (UGT) 1A1*28, which confirms Gilbert`s syndrome - a chronic mild form of unconjugated hyperbilirubinemia, caused by a decreased enzymatic activity of UGT, containing a two base-pair addition in the TATA element of the promoter, giving rise to seven [A(TA)7TAA] rather than the more usual six repeats [A(TA)6TAA]. The presence of this expanded el­ement has been shown to decrease the expression of the UGT-1A gene and has been recently identified as one of the co-factors determining the increase in bilirubin levels in patients with β-thalassemia.

Conclusion: The case presented shows that the (TA)7/(TA)7 genotype in patients with Gilbert`s syn­drome, is capable of modifying the clinical phenotype of β-thalassemia intermedia making the de­gree of jaundice more severe.


Thalassemia intermedia; Gilbert`s syndrome; hyperbilirubinemia



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