Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL‐receptor gene mutation

Abstract

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.

The Agenda for Familial Hypercholesterolemia

“…In patients with advanced cardiac disease, combined heart/liver transplantation has been performed. [179][180][181] …”

Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance

“…Thus, the liver transplantation can offer an efficient treatment for homozygous familial hypercholesterolemia [63][64][65].…”

Clinical observations and treatment of pediatric homozygous familial hypercholesterolemia due to a low-density lipoprotein receptor defect

“…42,43 Two of our patients received liver transplants with very good results. Their cholesterol levels are maintained in an appropriate range with a regular dose of statin.…”