Abnormal cholesterol metabolism in the Smith‐Lemli‐Opitz syndrome: Report of clinical and biochemical findings in four patients and treatment in one patient

Abstract

We report on four patients with the Smith-Lemli-Opitz (SLO) syndrome who appear to have a defect in cholesterol biosynthesis. The initial results of therapy of one of the patients with cholesterol and bile acids to correct her metabolic abnormalities are described. This finding provides a biochemical marker to help in the diagnosis of this syndrome, may provide insight into the pathogenesis of this disorder, and have therapeutic and prenatal diagnostic implications as well.

Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration

“…There are a number of instances in which disturbance of cholesterol metabolism in the CNS may be etiologically related to the onset of neurological diseases (38)(39)(40). In ApoE knockout mice of advancing age, there is also lipid deposition in astrocytes in the globus pallidus and substantia nigra (41).…”

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

“…As a consequence, rates of cholesterol synthesis are very high in the growing organs of the developing fetus and newborn animal (3)(4)(5). Any mutation that limits the availability of this critical molecule during development leads either to intrauterine death of the embryo or to major developmental abnormalities in the newborn (6)(7)(8). Even after maturity is reached and organs attain their adult size, there is continuous replacement, or "turnover," of cholesterol in the membranes of cells.…”

Intestinal Absorption of Cholesterol by Patients with Smith-Lemli-Opitz Syndrome

“…However, the efficiency of cholesterol absorption in these patients is not known. Abnormal bile acids in SLOS patients have been reported (6,27). In our sterol balance study, although it was not statistically significant, somewhat lower bile acid excretion in these patients was observed (25).…”