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. The authors report the effects of transmission of a known pathogenic mutation of the low-density lipoprotein receptor gene through liver transplantation, resulting in severe hypercholesterolemia.