title: Sickle liver disease--an unusual presentation in a compound heterozygote for HbS and a novel beta-thalassemia mutation.
abstract: A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the beta-globin genes showed he was a compound heterozygote for the Hbs mutation at codon 6 (CAG --> GTG) and a novel mutation at position 844 of intron 2 (betaIVS2-844 C --> A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London SE5 9RS, United Kingdom. tjscross@hotmail.com
authors.forename: Timothy J S
authors.initials: TJ
authors.lastname: Cross
authors.forename: Philip A
authors.initials: PA
authors.lastname: Berry
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Akbar
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.forename: S L
authors.initials: SL
authors.lastname: Thein
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000473:pathology; D001201:Ascites / Q000000981:diagnostic imaging; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000473:pathology / Q000601:surgery; D003062:Codon; D017809:Fatal Outcome; D005355:Fibrosis / Q000473:pathology / Q000601:surgery; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008099:Liver / Q000473:pathology / Q000601:surgery; D008297:Male; D009102:Multiple Organ Failure / Q000473:pathology; D009154:Mutation; D011860:Radiography, Abdominal / Q000379:methods; D018805:Sepsis / Q000150:complications / Q000473:pathology; D013163:Splenomegaly / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed / Q000379:methods; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D006451:Hemoglobin, Sickle