Background: Patients with homozygous and compound heterozygous familial hypercholesterolemia (FH) have markedly elevated plasma LDL cholesterol (LDL-C) from birth. If untreated, patients develop cardiovascular atherosclerosis resulting in death before the second decade of life. Medication and apheresis are only partially effective in reducing LDL-C levels, and do not significantly improve the prognosis. Liver transplantation (LT) can nearly normalize the cholesterol metabolism. We report a first case received domino LT in early infancy as a pre-emptive, rather than preventive therapy for compound heterozygous FH.
Case presentation: A 1-year-old girl was referred to our institution with xanthoma and hypercholesterolemia. Her serum cholesterol levels were extremely elevated; total cholesterol 1007 mg/dl and LDL-C 867 mg/dl. She was diagnosed as having FH with apparent family history in both parents. She has been treated on low-fat diet and medication with ezetimibe, bile acid sequestrants, and statins, however, maximal medical treatment could not lower her cholesterol levels. Genetic analysis revealed compound heterozygote for LDLR gene (c.IVS12+2T>C/c.418G>A), and enzyme assay showed 0% in lymphocytic LDL receptor activity. When she was 2-year-old, a cardiac catheterization was performed and no pathological changes were found in coronary arteries. We recommended LT to the family before vascular changes occur. Living donor LT from the family was not recommended because of the elevation of LDL-C. Eventually there was an opportunity to perform domino LT from the donor with maple syrup urine disease, which was accepted by the family. Her cholesterol levels dramatically normalized right after the donor liver was fixed in her. Postoperative course was uncomplicated, and her xanthomas are gradually fading in color and regressing.
Conclusion: LT for severe FH performed in early infancy before onset/progression of atherosclerosis is pre-emptive treatment rather than prevention. Domino liver transplantation is currently a good option of treatment for severe FH.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology