Publicação
Rotor syndrome presenting as Dubin-Johnson syndrome
| Resumo: | A 42-year-old man with no relevant past medical history presented with intermittent mild icterus and no signs of chronic liver disease. Laboratory tests were notable for hyperbilirubinemia (total 7.97 mg/dL, direct 5.37 mg/dL), bilirubinuria, no signs of hemolysis, normal liver tests and lipids profile. Abdominal ultrasound was unremarkable. A panel of chronic liver diseases was negative except for increased serum (147.4 μg/dL) and urinary (179 μg/24 h) copper, with normal ceruloplasmin. No other Leipzig criteria for Wilson's disease were found, including a negative test for ATP7B gene mutations (by exome sequencing). Total urinary coproporphyrin was normal with predominance of isomer I (86% of total urinary coproporphyrin output). Clinical and laboratorial profile was compatible with Dubin-Johnson syndrome; however, exome sequencing and search for deletions in the ABBC2 gene (encoding MRP2) only found a heterozygous potentially pathogenic variant (c.1483A>G - p.Lys495Glu). Additional extended molecular analysis of genes implicated in bilirubin metabolism found a homozygous deletion of a region encompassing exons 4-16 of SLCO1B3 gene (encoding OATP1B3) and all SLCO1B1 exons (encoding OATP1B1), thereby establishing Rotor syndrome diagnosis. Rotor and Dubin-Johnson syndromes are rare autosomal recessive liver diseases characterized by chronic conjugated hyperbilirubinemia, caused by the absence of the hepatic function OATP1B1/B3 (leading to impaired hepatic bilirubin reuptake and storage) and MRP2 transporters (leading to impaired hepatic bilirubin excretion), respectively. We report a case of compound hereditary hyperbilirubinemia with a misleading presentation with special focus on its diagnosis, particularly the advantage of extensive unbiased genetic testing by dedicated laboratories. With this case, we aim to highlight the necessity of establishing a diagnosis, reassuring the patient, and avoiding unnecessary invasive and costly diagnostic procedures. |
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| Autores principais: | Morais, Mariana B |
| Outros Autores: | Couvert, Philippe; Jéru, Isabelle; Machado, Mariana |
| Assunto: | ABCC2/MRP2 Conjugated hyperbilirubinemia Dubin-Johnson syndrome Rotor syndrome SLCO1B3/OATP1B |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | A 42-year-old man with no relevant past medical history presented with intermittent mild icterus and no signs of chronic liver disease. Laboratory tests were notable for hyperbilirubinemia (total 7.97 mg/dL, direct 5.37 mg/dL), bilirubinuria, no signs of hemolysis, normal liver tests and lipids profile. Abdominal ultrasound was unremarkable. A panel of chronic liver diseases was negative except for increased serum (147.4 μg/dL) and urinary (179 μg/24 h) copper, with normal ceruloplasmin. No other Leipzig criteria for Wilson's disease were found, including a negative test for ATP7B gene mutations (by exome sequencing). Total urinary coproporphyrin was normal with predominance of isomer I (86% of total urinary coproporphyrin output). Clinical and laboratorial profile was compatible with Dubin-Johnson syndrome; however, exome sequencing and search for deletions in the ABBC2 gene (encoding MRP2) only found a heterozygous potentially pathogenic variant (c.1483A>G - p.Lys495Glu). Additional extended molecular analysis of genes implicated in bilirubin metabolism found a homozygous deletion of a region encompassing exons 4-16 of SLCO1B3 gene (encoding OATP1B3) and all SLCO1B1 exons (encoding OATP1B1), thereby establishing Rotor syndrome diagnosis. Rotor and Dubin-Johnson syndromes are rare autosomal recessive liver diseases characterized by chronic conjugated hyperbilirubinemia, caused by the absence of the hepatic function OATP1B1/B3 (leading to impaired hepatic bilirubin reuptake and storage) and MRP2 transporters (leading to impaired hepatic bilirubin excretion), respectively. We report a case of compound hereditary hyperbilirubinemia with a misleading presentation with special focus on its diagnosis, particularly the advantage of extensive unbiased genetic testing by dedicated laboratories. With this case, we aim to highlight the necessity of establishing a diagnosis, reassuring the patient, and avoiding unnecessary invasive and costly diagnostic procedures. |
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