Sitosterolemia (Phytosterolemia) Differential Diagnoses

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

2. Merkens LS, Myrie SB, Steiner RD, Mymin D. Sitosterolemia. Gene Reviews. 2013. [QxMD MEDLINE Link].

3. Vecka M, Zak A, Tvrzicka E. Noncholesterol sterols. Acta Univ Carol Med Monogr. 2008. 154:5-101. [QxMD MEDLINE Link].

4. Patil S, Kharge J, Bagi V, Ramalingam R. Tendon xanthomas as indicators of atherosclerotic burden on coronary arteries. Indian Heart J. 2013 Jul-Aug. 65(4):491-2. [QxMD MEDLINE Link].

5. 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. 2010 Aug. 33(4):437-43. [QxMD MEDLINE Link].

6. McDaniel AL, Alger HM, Sawyer JK, Kelley KL, Kock ND, Brown JM, et al. Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am J Pathol. 2013 Apr. 182(4):1131-8. [QxMD MEDLINE Link]. [Full Text].

7. Myrie SB, Mymin D, Triggs-Raine B, Jones PJ. Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol supplementation in phytosterolemia heterozygotes and control individuals. Am J Clin Nutr. 2012 Apr. 95(4):837-44. [QxMD MEDLINE Link]. [Full Text].

8. Ajagbe BO, Othman RA, Myrie SB. Plant Sterols, Stanols, and Sitosterolemia. J AOAC Int. 2015 May-Jun. 98 (3):716-23. [QxMD MEDLINE Link].

9. Wang J, Mitsche MA, Lütjohann D, Cohen JC, Xie XS, Hobbs HH. Relative roles of ABCG5/ABCG8 in liver and intestine. J Lipid Res. 2015 Feb. 56 (2):319-30. [QxMD MEDLINE Link].

10. Tada H, Nohara A, Inazu A, Sakuma N, Mabuchi H, Kawashiri MA. Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease. J Atheroscler Thromb. 2018 Sep 1. 25 (9):783-789. [QxMD MEDLINE Link].

11. Lee JH, Song DY, Jun SH, Song SH, Shin CH, Ki CS, et al. High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence. PLoS One. 2020. 15 (8):e0238079. [QxMD MEDLINE Link].

12. Tanaka H, Watanabe Y, Hirano S, Tada H, Nomura A, Kawashiri MA, et al. Sitosterolemia Exhibiting Severe Hypercholesterolemia with Tendon Xanthomas Due to Compound Heterozygous ABCG5 Gene Mutations Treated with Ezetimibe and Alirocumab. Intern Med. 2020 Dec 1. 59 (23):3033-3037. [QxMD MEDLINE Link].

13. Tada H, Okada H, Nomura A, Yashiro S, Nohara A, Ishigaki Y, et al. Rare and Deleterious Mutations in ABCG5/ABCG8 Genes Contribute to Mimicking and Worsening of Familial Hypercholesterolemia Phenotype. Circ J. 2019 Aug 23. 83 (9):1917-1924. [QxMD MEDLINE Link].

14. Tada MT, Rocha VZ, Lima IR, Oliveira TGM, Chacra AP, Miname MH, et al. Screening of ABCG5 and ABCG8 Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program. Circ Genom Precis Med. 2022 Jun. 15 (3):e003390. [QxMD MEDLINE Link].

15. Xu L, Wen W, Yang Y, Xie J, Li R, Wu Y, et al. Features of Sitosterolemia in Children. Am J Cardiol. 2020 May 1. 125 (9):1312-1316. [QxMD MEDLINE Link].

16. Mekchay P, Ittiwut C, Ittiwut R, Akkawat B, Le Grand SM, Leela-Adisorn N, et al. Whole exome sequencing for diagnosis of hereditary thrombocytopenia. Medicine (Baltimore). 2020 Nov 20. 99 (47):e23275. [QxMD MEDLINE Link].

17. Goodyer M, Lovey J, Menétrey MJ. Peripheral blood features of phytosterolaemia. Br J Haematol. 2015 Dec. 171 (5):669. [QxMD MEDLINE Link].

18. Gok V, Tada H, Ensar Dogan M, Alakus Sari U, Aslan K, Ozcan A, et al. A teenager boy with a novel variant of Sitosterolemia presented with pancytopenia. Clin Chim Acta. 2022 Apr 1. 529:61-66. [QxMD MEDLINE Link].

19. Othman RA, Myrie SB, Mymin D, Merkens LS, Roullet JB, Steiner RD, et al. Ezetimibe reduces plant sterol accumulation and favorably increases platelet count in sitosterolemia. J Pediatr. 2015 Jan. 166 (1):125-31. [QxMD MEDLINE Link].

20. Deng L, Xu J, Chen W, Guo S, Steiner RD, Chen Q, et al. Remediation of ABCG5-Linked Macrothrombocytopenia With Ezetimibe Therapy. Front Genet. 2021. 12:769699. [QxMD MEDLINE Link].

21. 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. 2006 Oct. 91(10):1392-5. [QxMD MEDLINE Link].

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

23. Othman RA, Myrie SB, Mymin D, Roullet JB, DeBarber AE, Steiner RD, et al. Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. J Pediatr. 2017 Jun 15. [QxMD MEDLINE Link].

24. Bazerbachi F, Conboy EE, Mounajjed T, Watt KD, Babovic-Vuksanovic D, Patel SB, et al. Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but Fatal If Missed. Ann Hepatol. 2017 November-December. 16 (6):970-8. [QxMD MEDLINE Link].

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

26. 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. 2007 Jul. 61(7):896-905. [QxMD MEDLINE Link].

27. 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. 2011 May 23. [QxMD MEDLINE Link].

28. Renner C, Connor WE, Steiner RD. Sitosterolemia Presenting as Pseudohomozygous Familial Hypercholesterolemia. Clin Med Res. 2016 Jun. 14 (2):103-8. [QxMD MEDLINE Link].

29. 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. 2008 Nov-Dec. 24(11-12):1145-52. [QxMD MEDLINE Link].

30. Buonuomo PS, Iughetti L, Pisciotta L, Rabacchi C, Papadia F, Bruzzi P, et al. Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia. Atherosclerosis. 2017 Jul. 262:71-77. [QxMD MEDLINE Link].

31. Neff AT. Sitosterolemia's stomatocytosis and macrothrombocytopenia. Blood. 2012 Nov 22. 120(22):4283. [QxMD MEDLINE Link].

32. Othman RA, Myrie SB, Jones PJ. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia. Atherosclerosis. 2013 Dec. 231 (2):291-9. [QxMD MEDLINE Link].

33. Yagasaki H, Nakane T, Toda T, Kobayashi K, Aoyama K, Ichikawa T, et al. Carotid intima media thickness in a girl with sitosterolemia carrying a homozygous mutation in the ABCG5 gene. J Pediatr Endocrinol Metab. 2017 Aug 28. 30 (9):1007-11. [QxMD MEDLINE Link].

34. Xia Y, Duan Y, Zheng W, Liang L, Zhang H, Luo X, et al. Clinical, genetic profile and therapy evaluation of 55 children and 5 adults with sitosterolemia. J Clin Lipidol. 2022 Jan-Feb. 16 (1):40-51. [QxMD MEDLINE Link].

35. Othman RA, Myrie SB, Mymin D, Merkens LS, Roullet JB, Steiner RD, et al. Ezetimibe reduces plant sterol accumulation and favorably increases platelet count in sitosterolemia. J Pediatr. 2015 Jan. 166 (1):125-31. [QxMD MEDLINE Link].

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

37. 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. 2008 Oct. 62(10):1499-510. [QxMD MEDLINE Link].

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

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

40. 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.

41. Othman RA, Myrie SB, Mymin D, Roullet JB, Steiner RD, Jones PJH. Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia. Atherosclerosis. 2017 May. 260:27-33. [QxMD MEDLINE Link].

42. Lee JH, Song DY, Jun SH, Song SH, Shin CH, Ki CS, et al. High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence. PLoS One. 2020. 15 (8):e0238079. [QxMD MEDLINE Link].

Robert D Steiner, MD, FAAP, FACMG Professor (Clinical), Department of Pediatrics, University of Wisconsin School of Medicine and Public Health; Editor-in-Chief, Genetics in Medicine; Chief Medical Officer, PreventionGenetics

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: PreventionGenetics, ACMG, Acer Therapeutics, Biomarin; Best Doctors, Health Advances, Precision for Health, PTC Therapeutics, CTX Alliance, Aeglea, Eton, Leadiant<br/>Serve(d) as a speaker or a member of a speakers bureau for: France Foundation, Medscape<br/>Received research grant from: Alexion<br/>Received income in an amount equal to or greater than $250 from: Marshfield Clinic, France Foundation, Medscape, PreventionGenetics, ACMG, Acer Therapeutics; Raptor, Retrophin/Travere, Censa; Biomarin; Best Doctors, Health Advances, Precision for Health, PTC Therapeutics, Aeglea, Leadiant<br/>Travel Support for: CTX Alliance.

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.

Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

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

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