Two cases in one family of living donor liver transplantation for homozygous familial hypercholesterolemia

Abstract

We experienced two pediatric patients homozygous for familial hypercholesterolemia (FH) who received living donor liver transplantation (LDLT) from their parents, who were heterozygous for FH. The elder brother presented orange cutaneous xanthomas and was diagnosed homozygous FH at the age of 1 year. The plasma lipidogram showed that total cholesterol was 898 mg/dl, LDL cholesterol was 756 mg/dl, and the triglycerides level was 60 mg/dl. Cardiac ultrasonography showed no abnormal findings. He and his father had the same gene mutation of the LDL receptor. There were no ABO-compatible living donors with a normal LDL receptor in their family, and it was difficult to find a deceased donor in Japan; thus, he underwent LDLT with his father as the donor. The donor was heterozygous for FH, but we speculated that after LDLT total cholesterol could be controlled with anticholesterol agents. The graft was the lateral segment, and he was administered methylprednisolone and tacrolimus as immunosuppressive therapy. His liver function tests (LFTs) normalized immediately after transplantation, and his cholesterol has remained controlled at about 280 mg/dl with HMG-CoA reductase for 5 years after LDLT.His sister was born 2 years after his LDLT. The family had been well informed of the risk of having another baby heterozygous for FH. The plasma lipidogram showed that her total cholesterol was 857 mg/dl, LDL cholesterol was 689 mg/dl, and the triglycerides level was 173 mg/dl just after birth. She had symmetrical skin lesions on her hands. We informed the family that it was going to be very difficult to find a deceased donor, and the baby underwent ABO-incompatible LDLT with her mother as the donor at the age of 2 years. We performed plasma exchange twice before treatment to reduce the IgM and IgG hemagglutinin titers. One year after LDLT, her cholesterol remained stable at about 240 mg/dl under treatment with HMG-CoA reductase. At present, the four patients, including the two donors, are leading a normal daily life.FH is a disease caused by a mutant gene on chromosome 19 coding for the structure of the LDL receptor. 1 In the homozygous state, which occurs in only 1 in 1 million people, atherosclerosis progresses much more rapidly, producing cardiovascular disease and even causing death within the first two decades of life. LDL apheresis was introduced even for small children, but it has many difficulties such as long-term maintenance of blood access and a poor quality of life. Gene therapy has also been attempted, but it proved to be inefficient. Liver transplantation as a curative treatment for homozygous FH was introduced in 1984 2 because approximately 70% of LDL receptors are located in the liver. In Japan deceased donors are scarce, so LDLT is more feasible for homozygous FH. 3 Our patients showed that LDLT from a heterozygous or even an ABO-incompatible donor is effective for patients with homozygous FH, provided they are maintained on cholesterol-lowering drugs after transplantation. Fig. 2. a Minute, nodular, poorly circum...

Marginal parental donors for pediatric living donor liver transplantation

“…Three LDLT cases were reported utilizing donors with heterozygous familial hypercholesterolemia, where both donor and recipient were maintained on cholesterol-lowering drugs after transplantation. The long-term outcome was, however, not well demonstrated [18,19]. LDLT with a heterozygous donor with familial hypercholesterolemia might lead to some alleviation of low-density lipoprotein cholesterol and could induce premature atherosclerotic cardiovascular disease, either in the recipient or donor in the long term.…”