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2017, Number 6

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Ann Hepatol 2017; 16 (6)

Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but Fatal If Missed

Bazerbachi F, Conboy EE, Mounajjed T, Watt KD, Babovic-Vuksanovic D, Patel SB, Kamath PS

Language: Spanish
References: 26
Page: 970-978
PDF size: 516.88 Kb.


ABSTRACT

Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC) transporters that are responsible for the trafficking of xenosterols. Liver involvement is not a recognized manifestation of this disease, and cirrhosis has been reported only once in the medical literature. We describe a fatal case of a 21-year old South Asian male who presented with decompensated cirrhosis, and biochemical abnormalities consistent with sitosterolemia. Genetic testing showed a homozygous pathogenic mutation in ABCG5, confirming the diagnosis. Sitosterolemia is a rare, but likely under-recognized condition, and a high degree of suspicion is imperative to make the diagnosis. We propose that sitosterolemia should be included in the differential diagnosis for patients with cryptogenic cirrhosis, especially as there are effective oral therapies to treat this condition. Newly diagnosed sitosterolemia patients should undergo a thorough hepatology evaluation and follow-up to evaluate for the presence, development, and progression of any hepatic involvement.


REFERENCES

  1. Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 1974: 53: 1033-43. doi: 10.1172/ JCI107640.

  2. Patel SB, Salen G. Sitosterolemia: xenophobia for the body. In: Vissers MN, Kastelein JJP, Stroes ES (eds.). Evidencebased Management of Lipid Disorders. Harley: tfm Publishing Ltd; 2010. p. 217-30.

  3. Salen G, Ahrens EHJr, Grundy SM. Metabolism of beta-sitosterol in man. J Clin Invest 1970: 49: 952-67. doi: 10.1172/ JCI106315.

  4. Patel SB, Salen G, Hidaka H, Kwiterovich PO, Stalenhoef AFH, Miettinen TA, Grundy SM, et al. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J Clin Invest 1998: 102: 1041-4. doi: 10.1172/jci3963.

  5. Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, Ose L, et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet 2001: 69: 278-90.

  6. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 2001: 27: 79-83. doi: 10.1038/83799.

  7. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000: 290: 1771-5.

  8. Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB. Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology 2006: 130: 542-7.

  9. Fazio S, Linton MF. Evidence-based Management of Lipid Disorders. 2011.

  10. Kurvinen A, Nissinen MJ, Andersson S, Korhonen P, Ruuska T, Taimisto M, Kalliomaki M, et al. Parenteral plant sterols and intestinal failure-associated liver disease in neonates. J Pediatr Gastroenterol Nutrit 2012: 54: 803-11. doi: 10.1097/ MPG.0b013e3182474118.

  11. Mushtaq T, Wales JK, Wright NP. Adrenal insufficiency in phytosterolaemia. Eur J Endocrinol 2007: 157(Suppl. 1): S61-5. doi: 10.1530/EJE-07-0222.

  12. Hatanaka I, Yasuda H, Hidaka H, Harada N, Kobayashi M, Okabe H, Matsumoto K, et al. Spinal cord compression with paraplegia in xanthomatosis due to normocholesterolemic sitosterolemia. Ann Neurol 1990: 28: 390-3. doi: 10.1002/ ana.410280316.

  13. Salen G, Shefer S, Berginer V. Familial diseases with storage of sterols other than cholesterol: Cerebrotendinous xanthomatosis and sitosterolemia with xanthomatosis. In Stanbury JB, Wyngaarden JB, Frederickson DS, et al. (Eds): The Metabolic Basis of Inherited Disease. ed 5. New York: McGraw-Hill Book Co; 1982, pp. 713-24.

  14. Hidaka H, Nakamura T, Aoki T, Kojima H, Nakajima Y, Kosugi K, Hatanaka I, et al. Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. J Lip Res 1990: 31: 881-8.

  15. Gylling H, Vuoristo M, Farkkila M, Miettinen TA. The metabolism of cholestanol in primary biliary cirrhosis. J Hepatol 1996: 24: 444-51.

  16. Kurvinen A, Nissinen MJ, Andersson S, Korhonen P, Ruuska T, Taimisto M, Kalliomaki M, et al. Parenteral plant sterols and intestinal failure-associated liver disease in neonates. J Pediatr Gastroenterol Nutr 2012: 54: 803-11. doi: http:// dx.doi.org/10.1097/MPG.0b013e3182474118.

  17. Hukkinen M, Mutanen A, Nissinen M, Merras-Salmio L, Gylling H, Pakarinen MP. Parenteral Plant Sterols Accumulate in the Liver Reflecting Their Increased Serum Levels and Portal Inflammation in Children With Intestinal Failure. Jpen J Parenter Enteral Nutr 2016:9:9. doi: http://dx.doi.org/10.1177/ 0148607116637855.

  18. Li Y, Salfelder A, Schwab KO, Grünert SC, Velten T, Lütjohann D, Villavicencio-Lorini P, et al. Against all odds: blended phenotypes of three single-gene defects. Eur J Hum Genet 2016; 24: 1274-9.

  19. Mannucci L, Guardamagna O, Bertucci P, Pisciotta L, Liberatoscioli L, Bertolini S, Irace C, et al. Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene. Eur J Clin Invest 2007: 37: 997-1000.

  20. Lek M, Karczewski K, Minikel E, Samocha K, Banks E, Fennell T, O’Donnell-Luria A, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016: 536: 285–91. doi:10.1038/nature19

  21. Garg A. Dyslipidemias: Pathophysiology, Evaluation and Management. Springer; 2015.

  22. Wang Z, Cao L, Su Y, Wang G, Wang R, Yu Z, Bai X, et al. Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. Am J Hematol 2014: 89: 320-4. doi: http://dx.doi.org/10.1002/ajh.23619.

  23. Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson genetics in medicine. Elsevier Health Sciences; 2015.

  24. BIOBASE biological databases. Available at: URL. Access: 2016/10/09.

  25. Solca C, Tint GS, Patel SB. Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice. J Lipid Res 2013: 54: 397-409. doi: 10.1194/ jlr.M031476.

  26. Musliner T, Cselovszky D, Sirah W, McCrary Sisk C, Sapre A, Salen G, Lutjohann D, et al. Efficacy and safety of ezetimibe 40 mg vs. ezetimibe 10 mg in the treatment of patients with homozygous sitosterolaemia. Int J Clin Pract 2008: 62: 995- 1000. doi: http://dx.doi.org/10.1111/j.1742-1241.2008.01786.x.




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