Objectives: Smith-Lemli-Opitz syndrome (SLOS) is a recessively inherited disorder caused by an inborn error of cholesterol metabolism that results in deficiency of cholesterol and accumulation of the cholesterol precursor, 7-dehydrocholesterol (DHC) and its epimer, 8-DHC. Affected patients present with congenital anomalies, growth restriction, and mental retardation. Postnatal treatment with cholesterol supplementation has been shown to improve plasma sterol levels and has resulted in improved growth and development in many patients. We hypothesized that prenatal supplementation of cholesterol could potentially arrest some of the adverse consequences of cholesterol deficiency at an earlier stage of development.
Methods: SLOS was diagnosed in the third trimester in a fetus initially identified by sonography with intrauterine growth restriction and ambiguous genitalia and confirmed by elevated levels of 7- and 8-DHC in amniotic fluid. Antenatal supplementation of cholesterol was provided by fetal intravenous and intraperitoneal transfusions of fresh frozen plasma (cholesterol level = 219 mg/dl).
Results: The in utero transfusions resulted in increased levels of fetal cholesterol, as measured in blood samples obtained by cordocentesis. In addition, fetal red cell mean corpuscular volume rose, which further indicated that the exogenous cholesterol was incorporated into the fetal erythrocytes.
Conclusions: Antenatal treatment of SLOS by cholesterol supplementation is feasible and results in improvement in fetal plasma cholesterol levels and fetal red cell volume. SLOS may be added to the growing list of human genetic disorders for which prenatal diagnosis is available and therapeutic intervention may be possible.