title: Transmission of LDLR mutation from donor through liver transplantation resulting in hypercholesterolemia in the recipient.
abstract: Donor-transmitted disease in organ transplantation is uncommon, but possible. The LDL receptor (LDLR), a key regulator of lipoprotein metabolism, is abundant in the liver. Mutations in the LDLR gene, leading to reduced LDLR activity, are the main cause for familial hypercholesterolemia (FH). The estimated prevalence of FH is 1/200-1/500 in the population indicating that there are 14-34 million individuals with FH worldwide. We describe a patient who developed severe hypercholesterolemia after liver transplantation (LT). The 42-year-old female, who was transplanted because of hepatic epithelioid hemangioendothelioma with normal liver function, exhibited an increase in plasma total cholesterol from 5.6 mmol/L (217 mg/dL) pretransplant to 11.7 mmol/L (452 mg/dL) at 6 months posttransplant. The respective increase in LDL cholesterol was from 3.30 (128 mg/dL) to 8.99 mmol/L (348 mg/dL). At 1 year, total and LDL cholesterol levels were 11.0 (425 mg/dL) and 7.81 (302 mg/dL), respectively. Sequencing of the coding region of LDLR from a liver graft biopsy revealed a splicing heterozygous mutation of LDLR, whereas no FH-related mutation was found in DNA extracted from the patient's blood white cells. This confirmed the first reported case of a patient receiving a mutation in LDLR through LT. The case shows that a donor-transmitted disorder should not be overlooked as a possible cause for severe hypercholesterolemia.
authors.affiliation: Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Nikkilä
authors.forename: F
authors.initials: F
authors.lastname: Åberg
authors.forename: H
authors.initials: H
authors.lastname: Isoniemi
mesh_terms: D000328:Adult; D005260:Female; D018323:Hemangioendothelioma, Epithelioid / Q000235:genetics / Q000601:surgery*; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology*; D008113:Liver Neoplasms / Q000235:genetics / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011973:Receptors, LDL / Q000235:genetics*; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D011973:Receptors, LDL
keywords: Clinical research/practice; disease pathogenesis; donors and donation; genetics; hyperlipidemia; liver disease: congenital; liver transplantation/hepatology; translational research/science