Sitosterolemia Differential Diagnoses

  • Author: Robert D Steiner, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jul 6, 2011
 
 

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Robert D Steiner, MD  Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health and Science University School of Medicine; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director of Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA)

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Specialty Editor Board

Ian Krantz, MD  Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia

Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Patricia Campbell, MD, to the original writing and development of this article.

References

  1. Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest. Apr 1974;53(4):1033-43. [Medline].

  2. Vecka M, Zak A, Tvrzicka E. Noncholesterol sterols. Acta Univ Carol Med Monogr. 2008;154:5-101. [Medline].

  3. Niu DM, Chong KW, Hsu JH, Wu TJ, Yu HC, Huang CH, et al. Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children. J Inherit Metab Dis. Aug 2010;33(4):437-43. [Medline].

  4. Su Y, Wang Z, Yang H, Cao L, Liu F, Bai X. Clinical and molecular genetic analysis of a family with sitosterolemia and co-existing erythrocyte and platelet abnormalities. Haematologica. Oct 2006;91(10):1392-5. [Medline].

  5. Wang G, Wang Z, Liang J, Cao L, Bai X, Ruan C. A Phytosterolemia Patient Presenting Exclusively with Macrothrombocytopenia and Stomatocytic Hemolysis. Acta Haematol. May 12 2011;126(2):95-98. [Medline].

  6. Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB. Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology. Feb 2006;130(2):542-7. [Medline].

  7. Kratz M, Kannenberg F, Gramenz E, et al. Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols. Eur J Clin Nutr. Jul 2007;61(7):896-905. [Medline].

  8. Keller S, Prechtl D, Aslanidis C, Ceglarek U, Thiery J, Schmitz G, et al. Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: A case report. Eur J Med Genet. May 23 2011;[Medline].

  9. Llop JM, Virgili N, Moreno-Villares JM, García-Peris P, Serrano T, Forga M. Phytosterolemia in parenteral nutrition patients: implications for liver disease development. Nutrition. Nov-Dec 2008;24(11-12):1145-52. [Medline].

  10. Bhattacharrya AK, Connor WE. Familial diseases with storage of sterols other than cholesterol:. In: Stanbury B, Wyngaarden, Fredrickson DS, eds. The Metabolic Basis of Inherited Disease. 4th ed. New York, NY: McGraw-Hill; 1978:656-87.

  11. Kuksis I, Myher JJ, Marai L, et al. Fatty acid composition of individual plasma steryl esters in phytosterolemia and xanthomatosis. Lipids. 1986;21:371-7.

  12. Salen G, von Bergmann K, Lutjohann D, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. Mar 2 2004;109(8):966-71. [Medline].

  13. Lutjohann D, von Bergmann K, Sirah W, et al. Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study. Int J Clin Pract. Oct 2008;62(10):1499-510. [Medline].

  14. Salen G, Starc T, Sisk CM, Patel SB. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. Gastroenterology. May 2006;130(6):1853-7. [Medline].

  15. Berge KE, Tian H, Graf GA, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. Dec 1 2000;290(5497):1771-5. [Medline].

  16. Bhattacharyya AK, Connor WE, Lin DS, et al. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb. Sep-Oct 1991;11(5):1287-94. [Medline].

  17. Bjorkhem I, Boberg KM. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Scriver CR, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 7th ed. New York, NY: McGraw-Hill, Health Professions Division; 1995:2073-2102.

  18. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. May 2 1997;89(3):331-40. [Medline].

  19. Clayton PT, Bowron A, Mills KA, et al. Phytosterolemia in children with parenteral nutrition-associated cholestatic liver disease. Gastroenterology. Dec 1993;105(6):1806-13. [Medline].

  20. Cobb MM, Salen G, Tint GS. Comparative effect of dietary sitosterol on plasma sterols and cholesterol and bile acid synthesis in a sitosterolemic homozygote and heterozygote subject. J Am Coll Nutr. Dec 1997;16(6):605-13. [Medline].

  21. Ellegard L, Sunesson A, Bosaeus I. High serum phytosterol in short bowel patients on parenteral nutritionsupport. Clin Nutr. Jun 2005;24(3):415-20.

  22. Gregg RE, Connor WE, Lin DS, et al. Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis. J Clin Invest. Jun 1986;77(6):1864-72. [Medline].

  23. Hidaka H, Nakamura T, Aoki T, et al. Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. J Lipid Res. May 1990;31(5):881-8. [Medline].

  24. Honda A, Salen G, Honda M, et al. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts. J Lab Clin Med. Feb 2000;135(2):174-9. [Medline].

  25. Honda A, Salen G, Nguyen LB, et al. Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3- methylglutaryl-CoA synthase, reductase, squalene synthase, and 7- dehydrocholesterol delta7-reductase in liver and mononucle. J Lipid Res. Jan 1998;39(1):44-50. [Medline].

  26. Klett EL, Lu K, Kosters A, et al. A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. BMC Med. Mar 24 2004;2(1):5. [Medline].

  27. Ling WH, Jones PJ. Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci. 1995;57(3):195-206. [Medline].

  28. Lutjohann D, von Bergmann K. Phytosterolemia: diagnosis, characterization and therapeutical approaches. Ann Med. Jun 1997;29(3):181-4. [Medline].

  29. Mellies M, Glueck CJ, Sweeney C, et al. Plasma and dietary phytosterols in children. Pediatrics. Jan 1976;57(1):60-7. [Medline].

  30. Miettinen TA. Phytosterolemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur J Clin Invest. Feb 1980;10(1):27-35. [Medline].

  31. Nguyen LB, Shefer S, Salen G, et al. A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J Clin Invest. Sep 1990;86(3):923-31. [Medline].

  32. Nguyen LB, Shefer S, Salen G, et al. Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in the rat ileum: effects of bile acids and lovastatin. Metabolism. Nov 1994;43(11):1446-50. [Medline].

  33. Patel SB, Honda A, Salen G. Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis. J Lipid Res. May 1998;39(5):1055-61. [Medline].

  34. Patel SB, Salen G, Hidaka H, et al. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. Sep 1 1998;102(5):1041-4. [Medline].

  35. Salen G, Horak I, Rothkopf M, et al. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J Lipid Res. Sep 1985;26(9):1126-33. [Medline].

  36. Salen G, Shefer S, Nguyen L, et al. Sitosterolemia. J Lipid Res. Jul 1992;33(7):945-55. [Medline].

  37. Salen G, Shore V, Tint GS, et al. Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. J Lipid Res. Sep 1989;30(9):1319-30. [Medline].

  38. Salen G, Tint GS, Shefer S, et al. Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia. Arterioscler Thromb. May 1992;12(5):563-8. [Medline].

  39. Saubion JL, Hazane C, Jalabert M. The Role of Sterols in Lipid Emulsions for Parenteral Nutrition. Nutrition. 1998;14:477-8.

  40. Sehayek E. Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences. J Lipid Res. Nov 2003;44(11):2030-8. [Medline].

  41. Shefer S, Salen G, Bullock J, et al. The effect of increased hepatic sitosterol on the regulation of 3- hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7 alpha- hydroxylase in the rat and sitosterolemic homozygotes. Hepatology. Jul 1994;20(1 Pt 1):213-9. [Medline].

  42. Wang J, Joy T, Mymin D, Frohlich J, Hegele RA. Phenotypic heterogeneity of sitosterolemia. J Lipid Res. Dec 2004;45(12):2361-7. [Medline].

 
Previous
Next
 
Tuberous xanthomas. Courtesy of Duke University Medical Center.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.