Five years' experience of cholesterol treatment for the Smith-Lemli-Opitz Syndrome (SLOS): What have we learned, where are we going?

Abstract

Since January of 1994, following the discovery of the defect in cholesterol metabolism now known to cause SLOS, we have been treating SLOS patients with a concentrated suspension of cholesterol in soybean oil. Eighteen patients with SLOS, ranging in age from birth to mid teens, and ranging in pretreatment cholesterol levels from 8-90 mg/dl have been followed by us every 1-3 months for up to five years while on treatment.We will present data to show benefits of treatment in this cohort of patients. No adverse reactions to therapy have been noted. Benefits of therapy include improved growth and nutritional status, better tolerance of infection, and improvement in behavioral disturbances. Adrenal function and neutrophil function have been investigated, and both are normal. Ongoing studies are documenting neuropsychological course, CNS myelinization on MRI, and hearing status with ABR.We have discovered problems in our patients which were not previously known to occur in SLOS. These include photosensitivity, which we are now studying both in vitro in skin fibroblasts, and in vivo using timed exposure to UV light. We have also documented abnormal red cell shape (acanthocytosis), and the development of hypersplenism with thrombocytopenia in some patients. We are now accumulating experience in the management of profoundly ill neonates using fresh frozen plasma, and in prenatal diagnosis, by assessing low maternal serum estriol levels. Future plans include studies of cholesterol absorption, and the use of MR spectroscopy to assess CNS cholesterol metabolism. Our close follow-up of this patient cohort has allowed us to appreciate the complexities of issues seen in children with severe cholesterol deficiency, and to develop a greater understanding of the natural course of SLOS.