Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation.
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.
Schmidt
Hartmut H-J
HH
Transplantationshepatologie, Universitätsklinikum Münster, Münster, Germany. hepar@ukmuenster.de
Tietge
Uwe J F
UJ
Buettner
Janine
J
Barg-Hock
Hannelore
H
Offner
Gisela
G
Schweitzer
Susanne
S
Dedoussis
Giorgos V
GV
Rodeck
Burkhard
B
Kallfelz
Hans C
HC
Schlitt
Hans-Jürgen
HJ
Oldhafer
Karl
K
Klempnauer
Jürgen
J
D000293:Adolescent; D003241:Consanguinity; D003324:Coronary Artery Disease / Q000628:therapy*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics* / Q000601:surgery*; D016031:Liver Transplantation; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*; D017741:Survivors
D011973:Receptors, LDL