In 1964, the Journal of Pediatrics published an article with the following abstract:
Three unrelated male children have been found to have a strikingly similar pattern of multiple congenital anomalies which suggests a common etiology. In addition to relative microcephaly with mental retardation and hypertonicity, these patients have incomplete development of the external genitals and abnormalities of the face, hands, and feet…. No chromosomal abnormality was found and the cause remains obscure though the apparent occurrence of the same condition in a deceased sibling of one of the patients suggests a genetic determination. 1
The article was published by three pediatricians: Dr. David W Smith, Dr. Luc Lemli, and Dr. John Opitz, who became the…show more content… This enzyme is important in the human body because it moderates the final metabolic reaction in cholesterol production. Though the disease was first described by the three pediatricians in 1964, the discovery of the link between the disorder and the biosynthesis of cholesterol was not made until 1994. Several researches selected five patients who exhibited what were considered the classic features of SLOS and took blood samples to analyze the amounts of sterols in the plasma.3 What they found through capillary-column gas chromatography was that all five patients’ blood samples had similar but distinctively abnormal concentrations of cholesterol and 7-dehyrdrocholesterol, with their levels of cholesterol being below the 5th percentile and its precursor being around two-thousand times greater than the average population.3 It was this discovery which led to the determination that an issue in the biosynthesis of cholesterol was the overall cause for SLOS, with the responsible gene, DHCR7, being identified and replicated in a lab in 1998.4
Before exploring the effects of SLOS on a biochemical level, an explanation of the metabolism and function of cholesterol would be helpful. The majority of cholesterol produced in the human body is made in the liver, but all soma cells are capable of creating it. Cholesterol synthesis begins with the condensation of two acetyl-CoA molecules in the cytoplasm…show more content… Cholesterol by itselft is necessary for the building and maintaining cell membranes. It allows cells to maintain their membrane’s fluidity over a range of temperatures, and cholesterol structure limits membrane permeability to hydrogen and sodium ions across the phospholipid bilayer. Cholesterol is also found to be important in another structure of cell membranes: lipid rafts—which are sections of the membrane containing sterols (such as cholesterol), glycosphingolipids (glycolipids with amino alcohol named sphingosine attached), and gangliosides (glycosphingolipids with at least one n-acetylneuraminic acid)7—are structures which organize and regulate many different processes in the cell such as neurotransmission along with the assembly of signaling molecules.7
Cholesterol is also crucial due to it being a precursor of all steroid hormones such as sex hormones (such as progesterone and testosterone), mineralocorticoids (responsible for regulating ion—such as sodium—concentrations in the blood), glucocorticoids (integral for the metabolic regulation for proteins, carbohydrates, and fats), and bile acids (liver-made substances used to make the bile salts needed for digestive system to utilize fats and fat-soluble vitamins A, D, E, and
