| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Single LDL apheresis improves serum remnant-like particle-cholesterol, C-reactive protein, and malondialdehyde-modified-low-density lipoprotein concentrations in Japanese hypercholesterolemic subjects Kobayashi, J., S. Katsube, et al. (2002), Clin Chim Acta 321(1-2): 107-12. Abstract: BACKGROUND: Single low-density lipoprotein (LDL)-apheresis may affect serum remnant-like particle-cholesterol (RLP-C), C-reactive protein (CRP) and malondialdehyde-modified (MDA)-LDL concentrations. SUBJECTS AND METHODS: Six subjects with hypercholesterolemia (five men, one woman) were involved in this study. Mean age and body mass index of the study subjects were 58+/-3.1 years and 23.6+/-2.07 kg/m(2), respectively. Five of the subjects were diagnosed as heterozygous familial hypercholesterolemia (FH) because of having both marked hypercholesterolemia and Achilles tendon xanthomas. LDL apheresis was introduced and continued using a dextran sulfate cellulose adsorption column technique every 2 weeks. Serum RLP-C was measured using an immunoaffinity mixed gel containing anti-apolipoprotein A-I and anti-apolipoprotein B monoclonal antibody. Serum CRP was measured by latex-enhanced assay. Serum MDA-LDL was measured using monoclonal antibody against MDA-LDL (ML25). RESULTS: Combined treatment in the steady state pre-treatment yielded a total, LDL- and HDL-cholesterol, and TG concentrations of 5.39+/-0.81, 3.82+/-1.03, 1.24+/-0.29 and 0.92+/-0.43 mmol/l, respectively, and a post-treatment total, LDL- and HDL-cholesterol and TG concentrations of 2.79+/-0.37 (-48%, p<0.001), 1.63+/-0.29 (-57%, p<0.001), 1.18+/-0.26 (-5%, NS) and 0.23+/-0.11 mmol/l (-75%, p<0.001), respectively. Serum RLP-C and CRP concentrations showed a substantial reduction -73%, p<0.05 for RLP-C; -56%, p<0.05 for CRP during this procedure. In addition, LDL apheresis was found to also cause a marked reduction in serum MDA-LDL concentration (-61%, p<0.05). CONCLUSION: LDL-apheresis is an effective treatment for removing atherogenic factors RLP-C, CRP and MDA-LDL from sera. |
| Single molecular mechanics of a cholesterol-bearing pullulan nanogel at the hydrophobic interfaces Lee, I. and K. Akiyoshi (2004), Biomaterials 25(15): 2911-8. Abstract: The study of nanogel (hydrogel nanoparticle) has intensified in the last decade due to the enormous potential applications in biomimetics, biosensors, artificial muscles and drug delivery (or release) systems. Cholesterol-bearing pullulan (CHP) is composed of hydrophilic pullulan backbone and partly substituted hydrophobic cholesterol, and is capable of forming a stable hydrogel nanoparticle in aqueous solution due to the self-assembly of hydrophobic cholesterol moieties. The conformation of CHP changes dramatically at the hydrophobic interfaces. In order to understand the interfacial responses of CHP, the interaction forces of CHP nanogels to the hydrophobic HOPG (highly orientated pyrolytic graphite) or carbon-coated surfaces were measured using atomic force microscope. The freely jointed china model for CHP molecular elasticity was applied to the force-extension curves and debonding force-pull-off distance in order to estimate the contour lengths and the segment lengths of the CHP molecules. The segment length of CHP chains in aqueous solution was estimated 0.32+/-0.19 nm showing a very flexible chain. From our analysis of the dynamic force measurements, the debonding forces were shown to depend on the applied loading forces. The zero kinetic off-rate K(off)(0) and the transition state x(b) were estimated to be 1.1 x 10(-3)s(-1) and 2.9A, respectively. |
| Single repeat deletion in ApoA-I blocks cholesterol esterification and results in rapid catabolism of delta6 and wild-type ApoA-I in transgenic mice Sorci-Thomas, M. G., M. Thomas, et al. (2000), J Biol Chem 275(16): 12156-63. Abstract: The deletion mutation Delta6 apolipoprotein A-I lacks residues 143-164 or repeat 6 in the mature apoA-I protein. In vitro studies show this mutation dramatically reduces the rate of lecithin:cholesterol acyltransferase (LCAT) catalyzed cholesterol esterification. The present study was initiated to investigate the effect of this mutation on in vivo high density lipoprotein (HDL) cholesterol esterification and metabolism. Transgenic mice expressing human Delta6 apoA-I (TgDelta6 +/+) were created and then crossed with apoA-I knockout mice (-/-) to generate mice expressing only human Delta6 apoA-I (TgDelta6 -/-). Human Delta6 apoA-I was associated with homogeneous sized alpha-HDL, when wild-type mouse apoA-I was present (in TgDelta6 +/+ and +/- mice). However, in the absence of endogenous mouse apoA-I, Delta6 apoA-I was found exclusively in cholesterol ester-poor HDL, and lipid-free HDL fractions. This observation coincides with the 6-fold lower cholesterol ester mass in TgDelta6 -/- mouse plasma compared with control. Structural studies show that despite the structural perturbation of a domain extending from repeat 5 to repeat 8 (137-178), Delta6 apoA-I binds to spherical unilamellar vesicles with only 2-fold less binding affinity. In summary, these data show a domain corresponding to apoA-I repeat 6 is responsible for providing an essential conformation for LCAT catalyzed generation of cholesterol esters. Deletion of apoA-I repeat 6 not only blocks normal levels of cholesterol esterification but also exerts a dominant inhibition on the ability of wild-type apoA-I to activate LCAT in vivo. |
| Singlet oxygen adducts of cholesterol: photogeneration and reductive turnover in membrane systems Korytowski, W. and A. W. Girotti (1999), Photochem Photobiol 70(4): 484-9. Abstract: Identification of signature products provides a powerful means for establishing whether singlet molecular oxygen (1O2) is a reactive intermediate in a photodynamic process. This approach is particularly attractive for biological systems in which direct physical measurement is difficult because of the short lifetime of 1O2. Among the many possible reporter molecules in a target system, cholesterol (Ch) has the advantage of affording a limited number of readily distinguishable oxidation products, among which are the hydroperoxides 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH) and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH) that derive specifically from 1O2 addition. The purpose of this study was to compare these species in terms of (1) rates of accumulation in photodynamically treated liposomal membranes; (2) susceptibility to iron-mediated 1 e- reduction that triggers chain peroxidative damage; (3) susceptibility to selenoperoxidase (phospholipid hydroperoxide glutathione peroxidase PHGPX)-mediated 2 e- reduction that protects against such damage and (4) relative toxicity to mammalian cells. Our results indicate that 5 alpha-OOH is photogenerated at a much greater initial rate than 6 alpha-OOH or 6 beta-OOH. Although liposomal 5 alpha-OOH, 6 alpha-OOH, and 6 beta-OOH exhibit similar first-order decay kinetics during iron/ascorbate treatment, the former decays much more slowly during GSH/PHGPX treatment, and is more toxic to L1210 cells. These and related findings suggest that 5 alpha-OOH is potentially the most damaging ChOOH to arise in photodynamically treated cells. |
| Sitostanol administered in lecithin micelles potently reduces cholesterol absorption in humans Ostlund, R. E., Jr., C. A. Spilburg, et al. (1999), Am J Clin Nutr 70(5): 826-31. Abstract: BACKGROUND: Phytosterol feeding in human clinical trials has had generally small and inconsistent effects on serum cholesterol concentrations, raising doubts about the importance of phytosterols in natural diets and supplements. OBJECTIVE: The hypothesis tested was that the low intestinal bioavailability of purified phytosterols can be increased by formulation with lecithin. DESIGN: The ability of sitostanol to reduce cholesterol absorption was measured directly by including hexadeuterated cholesterol tracer in a standard test breakfast and measuring plasma tracer concentration 4 and 5 d later by gas chromatography-negative ion mass spectrometry. The tracer amount after a test meal containing sitostanol was compared with that after an identical meal containing placebo. Each subject served as his or her own control and the order of testing was random. Sitostanol was formulated either as a powder or as a sonicated micellar solution with lecithin. A total of 38 single-meal tests were performed in 6 healthy subjects. RESULTS: Sitostanol powder (1 g) reduced cholesterol absorption by only 11.3 +/- 7.4% (P = 0.2), confirming in vitro data showing poor solubility of sitostanol powder in artificial bile. In contrast, sitostanol in lecithin micelles reduced cholesterol absorption by 36.7 +/- 4.2% (P = 0.003) at a dose of 700 mg and by 34.4 +/- 5.8% (P = 0.01) at a dose of 300 mg. CONCLUSIONS: Sitostanol reduced cholesterol absorption at doses lower than reported previously, but only if presented in lecithin micelles. Properly formulated sitostanol as well as naturally occurring complexes of phytosterol and phospholipid might be therapeutically useful for cholesterol lowering. |
| Sitosterolaemia. Dietary cholesterol absorption Patel, S. (2001), Lancet 358 Suppl: S63. |
| Sitosterolemia: a gateway to new knowledge about cholesterol metabolism Berge, K. E. (2003), Ann Med 35(7): 502-11. Abstract: Sitosterolemia (OMIM 210250) is a rare, autosomal recessive lipid disorder initially described almost 30 years ago. The disease is characterized by elevated plasma levels of plant sterols due to increased intestinal absorption and reduced biliary secretion of neutral sterols. Patients with sitosterolemia are frequently hypercholesterolemic, and develop xanthomas and premature coronary heart disease (CHD). Hemolysis, arthralgias and arthritis are also frequently associated with the disorder. Recently, sitosterolemia has been revealed to be due to mutations in either of the two ATP-binding cassette (ABC) half-transporters. ABCG5 or ABCG8. These two genes are expressed almost exclusively in the liver and intestine, and are co-regulated by the nuclear hormone receptor, liver X receptor (LXR). Genetically modified mice, which express either high levels or no ABCG5 and ABCG8 have been developed. Analyses of these mice confirm that these two transporters play key roles in regulating the absorption of dietary and biliary sterols, and in mediating the excretion of neutral sterols from the liver to the bile. The elucidation of the gene defects responsible for sitosterolemia provides potential therapeutic targets for the treatment of hyperlipidemias in the general population. |
| Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis Patel, S. B., A. Honda, et al. (1998), J Lipid Res 39(5): 1055-61. Abstract: Sitosterolemia (phytosterolemia) is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, xanthomas, and increased plasma plant sterols and 5alpha-stanols. Affected individuals show an increased absorption of both cholesterol and sitosterol from the diet, decreased bile clearance of these sterols and their metabolites resulting in markedly expanded whole body cholesterol and sitosterol pools. Biochemical studies have shown that the regulation of the cholesterol biosynthetic pathway may be abnormal in this condition. In particular, the activities and mRNA for the biosynthetic enzymes, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase are low in liver biopsy specimens isolated from affected individuals, suggesting replete intracellular cholesterol pools. However, the membrane expression of hepatocyte low density lipoprotein receptors was increased, suggesting discordant regulation. Segregation analyses in three families for the genes for HMG-CoA reductase, HMG-CoA synthase, and LDL-receptor excluded these as sites of mutation. In view of the previously described discordant regulation of the above genes in sitosterolemia, the two major regulatory genes for this pathway, sterol regulatory element binding proteins (SREBP-1 and -2), were also examined. These genes did not segregate with the disease and were thus excluded. Two other genes involved in cholesterol absorption and chylomicron secretion, namely acyl coenzyme A:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP) were also examined for segregation and similarly excluded. Although the gene defect in sitosterolemia therefore remains to be elucidated, important candidate genes have been excluded. |
| Size and stability of dipalmitoylphosphatidylcholine/cholesterol unilamellar vesicles are affected by interaction with proteins Dini, L., A. Di Giulio, et al. (1991), Biochim Biophys Acta 1062(1): 108-12. Abstract: The effect of entrapping the enzyme ascorbate oxidase into dipalmitoylphosphatidylcholine/cholesterol vesicles, was studied by conventional transmission electron microscopy and freeze-fracture. The freeze-fracture technique has definitely demonstrated the unilamellar nature of empty and enzyme-loaded vesicles. Images of freeze-fractured and label-fractured liposomes also indicate that the observed reduction of vesicles volume could be related to the localization of ascorbate oxidase across the membrane. The membrane localization of ascorbate oxidase may explain the oxidation of externally added ascorbate by intact enzyme-loaded liposomes. Finally, the ageing of liposomes appears to be accelerated in the presence of proteins. |
| Skeletal muscle fiber distribution influences serum high-density lipoprotein cholesterol level Tikkanen, H. O., H. Naveri, et al. (1996), Atherosclerosis 120(1-2): 1-5. Abstract: Earlier we have shown a significant positive association between muscle fiber distribution, i.e. percentage of slow-twitch (ST) fibers in the vastus lateralis muscle, and serum high-density lipoprotein cholesterol (HDL-C) level. This association may be due to the fact that ST fibers have a high capacity for oxidative energy metabolism and a high number of surrounding capillaries. These fibers have a high capacity to metabolize fatty acids liberated by lipoprotein lipase (LPL) from triglyceride-rich lipoproteins. This in turn elevates serum HDL-C levels. Thus, a high percentage of ST fibers (ST-%) may be one factor having a beneficial effect on serum HDL-C concentration. A high ST-% may also increase the likelihood that a person will become involved in an endurance type of physical activity, which further increases serum HDL-C concentration by increasing further LPL activity in the capillary bed of skeletal muscle. In this paper we present a hypothetical background of the role that ST fibers may have on serum lipid and lipoprotein profile. |
| Skin tissue cholesterol (SkinTc) is related to angiographically-defined cardiovascular disease Sprecher, D. L., S. G. Goodman, et al. (2003), Atherosclerosis 171(2): 255-8. Abstract: Parallel changes associated with aging found in the vasculature and skin at necropsy, have prompted small preliminary studies to assess the relation between skin tissue cholesterol (SkinTc) and cardiovascular disease. While these studies have been suggestive, no formal investigation is available to test this association. It would, therefore, be valuable to determine whether a relation between SkinTc and angiographic narrowing actually exists, the latter representing one accepted measurement of coronary atherosclerosis. METHODS: Patients at three hospitals undergoing coronary angiography and not on lipid altering agents (n = 649) were examined for skinTc using a non-invasive method. Vessels were evaluated manually (number with stenosis > or = 50%). Clinical characteristics, current medication use, and Framingham global risk score were recorded. RESULTS: SkinTc was significantly higher in patients with angiographic disease (124 +/- 30 vs. 118 +/- 30, P = 0.02). After adjustment for traditional coronary artery disease risk factors, SkinTc provided 7% additional risk (per 10 SkinTc units) for angiographic disease. CONCLUSION: SkinTc, measured with a non-invasive method, is associated with the presence of coronary artery disease as determined by catheterization. Such an assay may eventually help stratify patient risk and target prevention efforts. |
| Sleep-related violence and low serum cholesterol: a preliminary study Agargun, M. Y., M. R. Sekeroglu, et al. (2002), Psychiatry Clin Neurosci 56(2): 195-8. Abstract: To examine whether there is a relationship between serum cholesterol level and sleep-related violence, we evaluated 15 patients with violent behavior during sleep (VBS) and 15 normal control subjects. The patient and control groups were matched for sex, age, and weight. There were 13 women and two men in each group. The patients with VBS had lower serum total cholesterol, triglyceride, and low-density lipoprotein levels than the healthy subjects. Low cholesterol may effect serotonergic neuronal activity and some types of 5-HT receptors, then may be related to violent behavior during sleep. |
| Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel Xu, Q. W., R. B. Scott, et al. (1996), Hepatology 23(6): 1664-72. Abstract: Impaired gallbladder motility is an established factor in cholesterol gallstone formation. We assessed whether altered small intestinal smooth muscle contractility with slow transit might potentiate gallstone formation by further impeding enterohepatic cycling of bile acids. Ground squirrels were fed a 1% or a trace (controls) cholesterol diet. Small intestinal transit was evaluated from 51Cr distribution in conscious, fasted animals 20 minutes after infusion into the proximal jejunum. Small intestinal and gallbladder smooth muscle contractility was determined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool size calculated by isotope dilution. Gas-liquid chromatography (GLC) assessed bile salt profile. In animals on the 1% cholesterol diet, aboral transit was significantly delayed, the maximal contractile response to bethanechol was markedly increased (P <.05) with no change in median effective concentration in either circular or longitudinal muscle strips from both the jejunum and ileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. Cholesterol saturation index and the fraction of deoxycholic acid in the pool doubled, whereas the total bile salt pool size remained unchanged in cholesterol-fed animals. In this model, a high-cholesterol diet is associated with altered small intestinal smooth muscle contractility and prolonged small intestinal transit, in addition to diminished gallbladder contractility. The resulting sluggish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol gallstone formation. |
| Sluggish small bowel motility is involved in determining increased biliary deoxycholic acid in cholesterol gallstone patients Azzaroli, F., G. Mazzella, et al. (1999), Am J Gastroenterol 94(9): 2453-9. Abstract: OBJECTIVE: Our aim was to establish whether small intestine transit time is defective in subjects with cholesterol gallstones. METHODS: We enrolled 10 patients (eight women, two men; mean age, 48.7 yr; mean body mass index BMI, 22.4 Kg/m2) with recently diagnosed cholelithiasis, with no liver pathology, who were not taking any drugs, and 11 comparable healthy volunteers (eight women, three men; mean age, 46.2 yr; mean BMI, 22.7 Kg/m2), who served as controls. All subjects underwent orocecal (by starch breath test technique and serum assays of salazopyrin), oroileal (by serum assays of tauroursodeoxycholic acid), and duodenoileal (by serum assays of taurocholic acid) transit times; cholesterol saturation index; and bile acid composition and gallbladder motility studies (by ultrasound). For serum assays, blood samples were collected over a period of 7 h. Gallbladder motility and orocecal transit time were evaluated simultaneously. RESULTS: All four means of assessing transit time gave longer times in cholesterol gallstone patients than in controls: orocecal transit time (salazopyrin) = 366 +/- 13 vs 258 +/- 16 min, p < 0.0005; orocecal transit time (starch breath test) = 415 +/- 139 vs 290 +/- 15 min, p < 0.01; duodenoileal transit time: 272 +/- 23 vs 205 +/- 23 min, p < 0.03; and oroileal transit time: 308 +/- 18 vs 230 +/- 19 min, p < 0.009. Cholesterol gallstone patients showed an increase in percent molar biliary deoxycholic acid (30% +/- 4.5% vs 16% +/- 1.3%, p < 0.02) and a decrease in percent molar cholic acid 32% +/- 2.2% vs 40% +/- 1.3%, p < 0.03) and chenodeoxycholic acid (34% +/- 3% vs 41% +/- 1.8%, p < 0.03), compared with controls; patients also had greater percent molar biliary cholesterol. A linear relationship (r2 = 0.6324, p = 0.0012) between biliary deoxycholic acid and small bowel transit time was found. Residual gallbladder volumes were larger in cholesterol gallstone patients (11.38 +/- 1.27 vs 7.55 +/- 0.39 ml, p < 0.04), whereas basal gallbladder volumes, although higher, did not reach statistical significance (24.25 +/- 2.41 vs 19.98 +/- 1.63 ml; p = ns). CONCLUSIONS: This study confirms that patients with cholesterol gallstones have delayed small bowel transit, defective gallbladder motor function, and increased biliary deoxycholic acid. Delayed small bowel transit may contribute to supersaturation of bile with cholesterol by increasing deoxycholic acid production. |
| Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous injection of lipoprotein cholesterol Chambers, C. M., M. P. McLean, et al. (1997), Am J Med Genet 68(3): 322-7. Abstract: A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol is their impaired ability to absorb cholesterol due to a deficiency of bile acids. Since intravenously administered lipoprotein cholesterol should not require bile acids for uptake into tissues, we tested the effects of this form of cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2% dietary cholesterol was most effective as it raised hepatic cholesterol levels to 1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were decreased to 760 micrograms/g. Similar responses were seen for heart, lung, kidney, and testes. Brain sterol levels were not significantly affected. AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity. Administration of dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA reductase activity to barely detectable levels. The data indicate that the combination of iv and dietary cholesterol was most effective in raising cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo cholesterol biosynthesis. |
| Smith-Lemli-Opitz syndrome with extremely low plasma cholesterol Bzduch, V., D. Behulova, et al. (2000), J Inherit Metab Dis 23(6): 638-9. |
| Smith-Lemli-Opitz syndrome: abnormal cholesterol biosynthesis de la Torre Verdu, M., M. Vazquez Lopez, et al. (1997), An Esp Pediatr 46(6): 617-20. |
| Smith-Lemli-Opitz syndrome: prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid Rossiter, J. P., K. J. Hofman, et al. (1995), Am J Med Genet 56(3): 272-5. Abstract: Until recently, the diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was made on the basis of clinical criteria alone. As a result, prenatal diagnosis has been possible only if sonography disclosed distinct fetal malformations in a subsequent pregnancy. However, the recent description of increased levels of 7-dehydrocholesterol (cholesta-5,7-dien-3 beta-ol) in patients with SLOS, most likely caused by a deficiency of 3 beta-hydroxysteroid-delta 7-reductase, has provided an apparently reliable biochemical marker for diagnosis of SLOS. To determine if this abnormality of sterol metabolism has utility for prenatal diagnosis of SLOS, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLOS was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7-dehydrocholesterol in plasma. Quantitative analysis by gas chromatography of sterols extracted from the amniotic fluid of both pregnancies revealed similar, markedly increased levels of 7-dehydrocholesterol and its precursor, lathosterol (cholest-7-en-3 beta-ol), both of which were undetectable in reference amniotic fluids. These findings suggest that abnormalities of cholesterol biosynthesis in SLOS may be sufficiently expressed in fetal life to permit prenatal diagnosis of this disorder by measurement of 7-dehydrocholesterol in amniotic fluid. |
| Smith-Lemli-Opitz syndrome: the first malformation syndrome associated with defective cholesterol synthesis Battaile, K. P. and R. D. Steiner (2000), Mol Genet Metab 71(1-2): 154-62. Abstract: Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition with multiple malformations, mental retardation, and growth failure, results from markedly reduced activity of the final enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol reductase (DHCR7). Clinical signs vary in severity, ranging from fetal loss to holoprosencephaly with multiple malformations to isolated syndactyly. The biochemical defect in SLOS is a deficiency of DHCR7, which results in an abnormally low cholesterol level, and increased amounts of intermediates of sterol biosynthesis. Animal models currently exist through the use of cholesterol biosynthesis inhibitors, from which a great deal has been learned. Pregnant rats treated with inhibitors of DHCR7 yield pups that have abnormal sterol profiles and craniofacial abnormalities characteristic of severe SLOS. Biochemical testing of human patients can be performed using gas chromatography/mass spectroscopy (GC/MS) to analyze the sterol content of tissues, amniotic fluid, or cell culture lysate. Numerous mutations have been identified in DHCR7 but seven individual mutations account for 67% of the total mutations reported in the literature. Clinical trials with SLOS are underway, with the goal of increasing the cholesterol concentration in the plasma and tissues through the administration of dietary cholesterol. Thus far, this approach has shown limited efficacy. Nevertheless, the recent identification of the biochemical and molecular genetic basis for SLOS is reason for optimism that the condition may one day yield to treatment. |
| Smith-Lemli-Opitz syndrome: treatment with cholesterol and bile acids Ullrich, K., H. G. Koch, et al. (1996), Neuropediatrics 27(2): 111-2. |