Long-standing unconjugated hyperbilirubinaemia disproportionate to β-thalassaemia trait: unmasking coexisting homozygous UGT1A1*28 Gilbert syndrome through stepwise diagnostic reasoning
Year: 2026
Type: article
Study design: Case Report
Abstract: A man in his late twenties presented with a 13-year history of icterus and dark urine, together with a short history of abdominal pain for 2.5 months. Biochemical evaluation demonstrated a total serum bilirubin of 9.46 mg/dL with an unconjugated fraction of 9.04 mg/dl, normal hepatocellular enzymes, and splenomegaly on abdominal ultrasonography. The peripheral blood film showed a microcytic, hypochromic picture with anisopoikilocytosis and mild red-cell fragmentation. Whole-exome sequencing identified a heterozygous pathogenic HBB c.92+5G>C splice-donor variant (IVS-I-5 G>C), confirming β-thalassaemia carrier status. The magnitude of unconjugated hyperbilirubinaemia was, however, disproportionate to trait alone, prompting a targeted search for a coexisting inherited disorder of bilirubin conjugation. UGT1A1 promoter fragment analysis revealed a homozygous (TA)7/(TA)7 (*28/*28) genotype, confirming Gilbert syndrome. Recognising the coexistence of the two disorders, rather than accepting a single incomplete diagnosis, altered counselling, drug-safety advice and reproductive planning. This case underscores that when unconjugated hyperbilirubinaemia is disproportionate to the demonstrable degree of haemolysis, a second inherited disorder of bilirubin metabolism should be actively sought.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225018317