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Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia

  1. David C. Rees1,†,
  2. Achille Iolascon2,
  3. Massimo Carella3,
  4. Aengus S. O'Marcaigh4,
  5. James R. Kendra5,
  6. Simon N. Jowitt6,
  7. J. K. Wales1,
  8. Ajay Vora1,
  9. M. Makris1,
  10. Nigel Manning1,
  11. Anna Nicolaou7,
  12. Julie Fisher8,
  13. Anuska Mann9,
  14. Samuel J. Machin10,
  15. Peter T. Clayton9,
  16. Paolo Gasparini11,
  17. Gordon W. Stewart12

Article first published online: 6 JUL 2005

DOI: 10.1111/j.1365-2141.2005.05599.x

Issue

British Journal of Haematology

British Journal of Haematology

Volume 130, Issue 2, pages 297–309, July 2005

Additional Information

How to Cite

Rees, D. C., Iolascon, A., Carella, M., O'Marcaigh, A. S., Kendra, J. R., Jowitt, S. N., Wales, J. K., Vora, A., Makris, M., Manning, N., Nicolaou, A., Fisher, J., Mann, A., Machin, S. J., Clayton, P. T., Gasparini, P. and Stewart, G. W. (2005), Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia. British Journal of Haematology, 130: 297–309. doi: 10.1111/j.1365-2141.2005.05599.x

Author Information

  1. 1

    Sheffield Children's Hospital, Royal Hallamshire Hospital, Sheffield, UK

  2. 2

    CEINGE, University of Foggia, Foggia and Department of Biochemistry and Molecular Biology, Università Federico II, Naples, Italy

  3. 3

    Division of Genetics, IRCCS, San Giovanni Rotondo, Italy

  4. 4

    Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland

  5. 5

    Burnley General Hospital, Casterton Avenue, Burnley, UK

  6. 6

    Stepping Hill Hospital, Poplar Grove, Stockport, UK

  7. 7

    School of Pharmacy, University of Bradford, Bradford, UK

  8. 8

    School of Chemistry, University of Leeds, Leeds, UK

  9. 9

    Institute of Child Health, University College London, London, UK

  10. 10

    Department of Haematology, University College Hospitals, London, UK

  11. 11

    TIGEM and Second University of Naples, Naples, Italy

  12. 12

    Department of Medicine, University College London, Rayne Institute, University Street, London, UK

  1. †

    Present address: Department of Haematology, Kings College Hospital, Denmark Hill, London, UK.

*Gordon W. Stewart, Department of Medicine, University College London, Rayne Institute, University Street, London WC1E 6JJ, UK. E-mail: g.stewart@ucl.ac.uk

  • †

    Present address: Department of Haematology, Kings College Hospital, Denmark Hill, London, UK.

Publication History

  1. Issue published online: 6 JUL 2005
  2. Article first published online: 6 JUL 2005
  3. Received 7 March 2005; accepted for publication 12 May 2005

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References

  • Adosraku, R., Choi, G., Constantinou-Kokotos, V., Anderson, M. & Gibbons, W. (1994) NMR lipid profiles of cells, tissues, and body fluids: proton NMR analysis of human erythrocyte lipids. Journal of Lipid Research, 35, 1925–1931.
  • Ballas, S.K., Clark, M.R., Mohandas, N., Colfer, H.F., Caswell, M.S., Bergren, M.O., Perkins, H.A. & Shohet, S.B. (1984) Red cell membrane and cation deficiency in Rh null syndrome. Blood, 63, 1046–1055.
  • Bays, H.E., Moore, P.B., Drehobl, M.A., Rosenblatt, S., Toth, P.D., Dujovne, C.A., Knopp, R.H., Lipka, L.J., Lebeaut, A.P., Yang, B., Mellars, L.E., Cuffie-Jackson, C. & Veltri, E.P. (2001) Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clinical Therapeutics, 23, 1209–1230.
  • von Behrens, W. (1975a) Mediterranean macrothrombocytopenia. Blood, 46, 199–208.
  • von Behrens, W. (1975b) Splenomegaly, macrothrombocytopenia and stomatocytosis in healthy Mediterranean subjects. Scandinavian Journal of Haematology, 14, 258–267.
    Direct Link:
  • Berge, K.E., Tian, H., Graf, G.A., Yu, L., Grishin, N.V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R. & Hobbs, H.H. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science, 290, 1771–1775.
  • Berger, G.M., Deppe, W.M., Marais, A.D. & Biggs, M. (1994) Phytosterolaemia in three unrelated South African families. Postgraduate Medical Journal, 70, 631–637.
  • Bhattacharyya, A.K. & Connor, W.E. (1974) Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. Journal of Clinical Investigation, 53, 1033–1043.
  • Bjorkhem, I., Boberg, K. & Leitersdorf, E. (2001) Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Metabolic and Molecular Basis of Inherited Disease (ed. by C.Scriver, A.Beaudet, W.Sly, D.Valle, B.Childs, K.Kinzler & B.Vogelstein), pp. 2961–2988. McGraw-Hill, New York, USA.
  • Born, G.V. & Wehmeier, A. (1979) Inhibition of platelet thrombus formation by chlorpromazine acting to diminish haemolysis. Nature, 282, 212–213.
  • Born, G.V., Bergquist, D. & Arfors, K.E. (1976) Evidence for inhibition of platelet activation in blood by a drug effect on erythrocytes. Nature, 259, 233–235.
  • Clark, M.R., Shohet, S.B. & Gottfried, E.L. (1993) Hereditary hemolytic disease with increased red blood cell phosphatidylcholine and dehydration: one, two, or many disorders? American Journal of Hematology, 42, 25–30.
    Direct Link:
  • Clayton, P.T., Bowron, A., Mills, K.A., Massoud, A., Casteels, M. & Milla, P.J. (1993) Phytosterolemia in children with parenteral nutrition-associated cholestatic liver disease. Gastroenterology, 105, 1806–1813.
  • Coles, S.E., Ho, M.M., Chetty, M.C., Nicolaou, A. & Stewart, G.W. (1999) Hereditary stomatocytosis with marked pseudohyperkalaemia. British Journal of Haematology, 104, 275–283.
    Direct Link:
  • Dacie, J.V. & Lewis, S.M. (1984) Practical Haematology, 5th edn. Churchill Livingstone, Edinburgh, UK.
  • Ducrou, W. & Kimber, R.J. (1969) Stomatocytes, haemolytic anaemia and abdominal pain in Mediterranean migrants. Some examples of a new syndrome. Medical Journal of Australia, ii, 1087–1091.
  • Evans, D.A. & Metz, J. (1999) Mediterranean macrothrombocytopenia revisited. Medical Journal of Australia, 171, 277–278.
  • Harrison, P., Briggs, C. & Machin, S.J. (2004) Platelet counting. Methods in Molecular Biology, 272, 29–46.
  • Hartwig, J.H. & Italiano, J.E. (2003) Life of the blood platelet. In: Blood: Principles and Practice of Hematology (ed. by R.Handin, S.Lux & T.Stossel), pp. 1049–1079. JB Lippincott, Philadelphia, USA.
  • Jain, M.K., Eskow, K., Kuchibhotla, J. & Colman, R.W. (1978) Correlation of inhibition of platelet aggregation by phenothiazines and local anesthetics with their effects on a phospholipid bilayer. Thrombosis Research, 13, 1067–1075.
  • Kindness, G., Williamson, F.B. & Long, W.F. (1980) Inhibitory effect of trifluoperazine on aggregation of human platelets. Thrombosis Research, 17, 549–554.
  • Klett, E.L., Lee, M.H., Adams, D.B., Chavin, K.D. & Patel, S.B. (2004a) Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine. Bio-Med Central Gastroenterology, 4, 21.
  • Klett, E.L., Lu, K., Kosters, A., Vink, E., Lee, M.H., Altenburg, M., Shefer, S., Batta, A.K., Yu, H., Chen, J., Klein, R., Looije, N., Oude-Elferink, R., Groen, A.K., Maeda, N., Salen, G. & Patel, S.B. (2004b) A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. Bio-Med Central Medicine, 2, 5.
  • Lanzara, C., Ficarella, R., Totaro, A., Chen, X., Roberto, R., Perrotta, S., Lasalandra, C., Gasparini, P., Iolascon, A. & Carella, M. (2003) Congenital dyserythropoietic anemia type II: exclusion of seven candidate genes. Blood Cells, Molecules and Diseases, 30, 22–29.
  • Lee, M.H., Lu, K., Hazard, S., Yu, H., Shulenin, S., Hidaka, H., Kojima, H., Allikmets, R., Sakuma, N., Pegoraro, R., Srivastava, A.K., Salen, G., Dean, M. & Patel, S.B. (2001a) Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nature Genetics, 27, 79–83.
  • Lee, M.H., Lu, K. & Patel, S.B. (2001b) Genetic basis of sitosterolemia. Current Opinion in Lipidology, 12, 141–149.
  • Lu, K., Lee, M.H., Hazard, S., Brooks-Wilson, A., Hidaka, H., Kojima, H., Ose, L., Stalenhoef, A.F., Mietinnen, T., Bjorkhem, I., Bruckert, E., Pandya, A., Brewer, H.B. Jr, Salen, G., Dean, M., Srivastava, A. & Patel, S.B. (2001) 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. American Journal of Human Genetics, 69, 278–290.
  • Merrick, M.V. (1994) Gall-bladder and colonic retention of SeHCAT: a re-evaluation. European Journal of Nuclear Medicine, 21, 988–990.
  • Mhawech, P. & Saleem, A. (2000) Inherited giant platelet disorders. Classification and literature review. American Journal of Clinical Pathology, 113, 176–190.
  • Mills, D.C.B. & Roberts, G.C.K. (1967) Membrane active drugs and the aggregation of human blood platelets. Nature, 213, 35–38.
  • Payne, M. (2001) Too young to have a heart attack. Lancet, 358, s64.
  • Salen, G., von Bergmann, K., Lutjohann, D., Kwiterovich, P., Kane, J., Patel, S.B., Musliner, T., Stein, P. & Musser, B. (2004) Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation, 109, 966–971.
  • Sankila, E.M., Tolvanen, R., van den Hurk, J.A., Cremers, F.P. & de la Chapelle, A. (1992) Aberrant splicing of the CHM gene is a significant cause of choroideremia. Nature Genetics, 1, 109–113.
  • Schrier, S.L., Zachowski, A. & Devaux, P.F. (1992) Mechanisms of amphipath-induced stomatocytosis in human erythrocytes. Blood, 79, 782–786.
  • Sehayek, E., Yu, H.J., von Bergmann, K., Lutjohann, D., Stoffel, M., Duncan, E.M., Garcia-Naveda, L., Salit, J., Blundell, M.L., Friedman, J.M. & Breslow, J.L. (2004) Phytosterolemia on the island of Kosrae: founder effect for a novel ABCG8 mutation results in high carrier rate and increased plasma plant sterol levels. Journal of Lipid Research, 45, 1608–1613.
  • Sheetz, M. & Singer, S.J. (1974) Biological membranes as bilayer couples: a molecular mechanism of drug-erythrocyte interactions. Proceedings of the National Academy of Sciences of the United States of America, 71, 4457.
  • Steiner, R.D. & Campbell, P. (2005) Sitosterolemia, eMedicine Journal. Available at: http://www.emedicine.com/ped/topic2110.htm
  • Stewart, G.W. (2004) Hemolytic disease due to membrane ion channel disorders. Current Opinion in Hematology, 11, 244–250.
  • Stewart, G.W. & Turner, E.J. (1999) The hereditary stomatocytoses and allied disorders: congenital disorders of erythrocyte membrane permeability to Na and K. Bailliere's Best Practice in Research and Clinical Haematology, 12, 707–728.
  • Stewart, G.W., O'Brien, H., Morris, S.A., Owen, J.S., Lloyd, J.K. & Amess, J.A.L. (1987) Stomatocytosis, abnormal platelets and pseudo-homozygous hypercholesterolaemia. European Journal of Haematology, 38, 376–380.
    Direct Link:
  • Sudhop, T., Lutjohann, D. & von Bergmann, K. (2005) Sterol transporters: targets of natural sterols and new lipid lowering drugs. Pharmacology and Therapeutics, 105, 333–341.
  • Walensky, L.D., Narla, M. & Lux, S.E. (2003) Disorders of the red blood cell membrane. In: Blood: Principles and Practice of Hematology (ed. by R.Handin, S.Lux & T.Stossel), pp. 1709–1858. JB Lippincott, Philadelphia, USA.
  • Wang, J., Joy, T., Mymin, D., Frohlich, J. & Hegele, R.A. (2004) Phenotypic heterogeneity of sitosterolemia. Journal of Lipid Research, 45, 2361–2367.
  • Watts, G.F. & Mitchell, W.D. (1992) Clinical and metabolic findings in a patient with phytosterolaemia. Annals of Clinical Biochemistry, 29(Pt 2), 231–236.
  • Yu, L., Von Bergmann, K., Lutjohann, D., Hobbs, H.H. & Cohen, J.C. (2003) Selective sterol accumulation in ABCG5/ABCG8 deficient mice. Journal of Lipid Research, 1, 1.
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