Splenomegaly, hypersplenism, and hereditary disorders with splenomegaly

Abstract

Splenomegaly, sometimes of massive extent, occurs in a large number of hereditary diseases, some relatively prevalent and others, rare to ultra-rare. Because physicians are often unfamiliar with the less common disorders, patients may suffer because of diagnostic delay or diagnostic error and may undergo invasive, non-innocuous procedures such as splenectomy that are potentially avoidable were the correct diagnosis suspected. In this review article, we discuss the definition and clinical ramifications of “massive” splenomegaly and describe several rare genetic disorders that are sometimes associated with marked splenic enlargement as well as four additional hereditary “splenomegalic” lysosomal storage diseases (cholesterol esterase storage disease, Niemann-Pick C disease, acid sphingomyelinase deficiency disease, Gaucher disease) in which approved or promising experimental treatments should generally obviate the need for palliative splenectomy. We also summarize current concepts about the appropriate use of splenectomy in patients with β-thalassemia, hereditary spherocytosis and Gaucher disease and discuss surgical alternatives to classical total splenectomy for these disorders.

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Weinreb, N. and Rosenbloom, B. (2013) Splenomegaly, hypersplenism, and hereditary disorders with splenomegaly. Open Journal of Genetics, 3, 24-43. doi: 10.4236/ojgen.2013.31004.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Lamb, P.M., Lund, A., Kanagasabay, R.R., Martin, A., Webb, J.A. and Reznek, R.H. (2002) Spleen size: How well do linear ultrasound measurements correlate with three-dimensional CT volume assessments? British Journal of Radiology, 75, 573-577.
[2] McCorkle, R., Thomas, B., Suffaletto, H. and Jehle, D. (2010) Normative spleen size in tall healthy athletes: Implications for safe return to contact sports after infectious mononucleosis. Clinical Journal of Sport Medicine, 20, 413-415. doi:10.1097/JSM.0b013e3181f35fe5
[3] Spielmann, A.L., DeLong, D.M. and Kliewer, M.A. (2005) Sonographic evaluation of spleen size in tall healthy athletes. AJR American Journal of Roentgenology Diagnostic Imaging and Related Sciences, 184, 45-49.
[4] Kercher, K.W., Matthews, B.D., Walsh, R.M., Sing, R.F., Backus, C.L. and Heniford, B.T. (2002) Laparoscopic splenectomy for massive splenomegaly. The American Journal of Surgery, 183, 192-196. doi:10.1016/S0002-9610(01)00874-1
[5] Swanson, T.W., Meneghetti, A.T., Sampath, S., Connors, J.M. and Panton, O.N. (2011) Hand-assisted laparoscopic splenectomy versus open splenectomy for massive splenomegaly: 20-year experience at a Canadian centre. Canadian Journal of Surgery, 54, 189-193. doi:10.1503/cjs.044109
[6] Zhu, J., Ye, H., Wang, Y., Zhao, T., Zhu, Y., Xie, Z., Liu, J., Wang, K., Zhan, X. and Ye, Z. (2011) Laparoscopic versus open pediatric splenectomy for massive splenomegaly. Surgical Innovation, 18, 349-353.
[7] Gielchinsky, Y., Elstein, D., Hadas-Halpern, I., Lahad, A., Abrahamov, A. and Zimran, A. (1999) Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease. British Journal of Haematology, 106, 812-816. doi:10.1046/j.1365-2141.1999.01616.x
[8] Hollak, C., Belmatoug, N., Cole, J.A., Vom Dahl, S., Deegan, P.B., Goldblatt, J., Rosenbloom, B., van Dussen, L., Tylki-Szymańska, A., Weinreb, N.J., Zimran, A. and Cappellini, M.D. (2012) Clinical characteristics associated with persisting thrombocytopenia in type 1 Gaucher patients treated with imiglucerase for 4 to 5 years. British Journal of Haematology, 158, 528-538. doi:10.1111/j.1365-2141.2012.09175.x PMid:22640238
[9] Jaroch, M.T., Broughan, T.A. and Hermann, R.E. (1986) The natural history of splenic infarction. Surgery, 100, 743-750.
[10] Chin, J.K.T., McCormick, P.A., Hilson, A.J.W., Burroughs, A.K. and McIntyre, N. (1993) Liver/spleen scintigraphy for diagnosis of splenic infarction in cirrhotic patients. Postgraduate Medical Journal, 69, 715-717. doi:10.1136/pgmj.69.815.715
[11] Ustun, C., Kutlar, F., Holley, L., Seigler, M., Burgess, R. and Kutlar, A. (2003) Interaction of sickle cell trait with hereditary spherocytosis: Splenic infarcts and sequestration. Acta Haematol, 109, 46-49. doi:10.1159/000067273
[12] Breuer, C., Janssen, G., Laws, H.J., Schaper, J., Mayatepek, E., Schroten, H. and Tenenbaum, T. (2008) Splenic infarction in a patient hereditary spherocytosis, protein C deficiency and acute infectious mononucleosis. European Journal of Pediatrics, 167, 1449-1452. doi:10.1007/s00431-008-0781-3 PMid:18604554
[13] Park, M.Y., Kim, J.A., Yi, S.Y., Chang, S.H., Um, T.H. and Lee, H.R. (2011) Splenic infarction in a patient with autoimmune hemolytic anemia and protein C deficiency. The Korean Journal of Hematology, 46, 274-278.
[14] Gilbert, H.S. (1985) Myeloproliferative disorders. Clinics in Geriatric Medicine, 1, 773-93. PMid:3868427
[15] Spangler, W.L. and Kass, P.H. (1999) Splenic myeloid metaplasia, histiocytosis, and hypersplenism in the dog (65 cases). Veterinary Pathology, 36, 583-593. doi:10.1354/vp.36-6-583 PMid:10568439
[16] Fishman, D. and Isenberg, D.A. (1997) Splenic involvement in rheumatic diseases. Seminars in Arthritis and Rheumatism, 27, 141-155. doi:10.1016/S0049-0172(97)80013-3
[17] Hadary, A., Dashkowsky, I., Rapaport, A. and Cozakov, J.C. (2008) Non-traumatic rupture of spleen: Can splenectomy be applied selectively? The Israel Medical Association Journal, 10, 889-891.
[18] Beutler, E. and Grabowski, G.A. (2001) Gaucher disease. In: Scriver, C.R., Beaudet, A.L., Sly, W.S., and Valle, D., Eds., The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York, 3635-3668.
[19] Stone, D.L., Ginns, E.I., Krasnewich, D. and Sidransky, E. (2000) Life-threatening splenic hemorrhage in two patients with Gaucher disease. American Journal of Hematology, 64, 140-142. doi:10.1002/(SICI)1096-8652(200006)64:2<140::AID-AJH14>3.0.CO;2-T
[20] Dingli, D., Mesa, R.A. and Tefferi, A. (2004) Myelofibrosis with myeloid metaplasia; new developments in pathogenesis and treatment. Internal Medicine Journal, 43, 540-547. doi:10.2169/internalmedicine.43.540
[21] el-Shazly, M.A. and Okello, D.O. (1994) Tropical splenomegaly syndrome: Who gets oesophageal varices? East African Medical Journal, 71, 768-770.
[22] Watanabe, Y., Mizukami, T., Egawa, T., Okamoto, S., Sakauchi, M., Takita, T., Suzuki, N. and Sakuma, M. (1999) A case of progressive systemic sclerosis complicated by idiopathic portal hypertension with severe anemia. Ryumachi, 39, 586-590.
[23] Se?il, M., G?ktay, A., Dicle, O. and Pirnar, T. (2001) Splenic vascular malformations and portal hypertension in hereditary hemorrhagic telangiectasia: Sonographic findings. Journal of Clinical Ultrasound, 29, 56-59. doi:10.1002/1097-0096(200101)29:1<56::AID-JCU10>3.0.CO;2-O
[24] Gusberg, R.J., Peterec, S.M., Sumpio, B.E. and Meier, G.H. (1994) Splenomegaly and variceal bleeding—Hemodynamic basis and treatment implications. Hepatogastroenterology, 41, 573-577.
[25] Singh, I.K., Bhatnagar, V., Gupta, A.K. and Seith, A. (2011) Correlation of splenic volume with hematological parameters, splenic vein diameter, portal pressure and grade of varices in extrahepatic portal vein obstruction in children. Pediatric Surgery International, 27, 467-471. doi:10.1007/s00383-010-2847-3
[26] James, S.P., Stromeyer, F.W., Stowens, D.W. and Barranger, J.A. (1982) Gaucher disease: Hepatic abnormalities in 25 patients. Progress in Clinical and Biological Research, 95, 131-142.
[27] Bandyopadhyay, R., Bandyopadhyay, S. and Maity, P.K. (2011) Gauchers disease presenting with portal hypertension. Indian Pediatr. , 48, 801-802.
[28] Jacobs, P., Maze, S., Tayob, F. and Harries-Jones, E.P. (1985) Myelofibrosis, splenomegaly, and portal hypertension. Acta Haematol, 74, 45-48. doi:10.1159/000206164
[29] Aessopos, A., Farmakis, D., Deftereos, S., Tsironi, M., Polonifi, A., Moyssakis, I., Diamanti-Kandaraki, E. and Papalambros, E. (2005) Cardiovascular effects of splenomegaly and splenectomy in beta-thalassemia. Annals of Hematology, 84, 353-357. doi:10.1007/s00277-004-1002-4
[30] Farmakis, D. and Aessopos, A. (2011) Pulmonary hypertension associated with hemoglobinopathies: Prevalent but overlooked. Circulation, 123, 1227-1232. doi:10.1161/CIRCULATIONAHA.110.988089
[31] Smedema, J.P. and Louw, V.J. (2007) Pulmonary arterial hypertension after splenectomy for hereditary spherocytosis. Cardiovascular Journal of Africa, 18, 84-89.
[32] Crary, S.E., Ramaciotti, C. and Buchanan, G.R. (2011) Prevalence of pulmonary hypertension in hereditary spherocytosis. American Journal of Hematology, 86, E73-E76. doi:10.1002/ajh.22182
[33] García-Manero, G., Schuster, S.J., Patrick, H. and Martinez, J. (1999) Pulmonary hypertension in patients with myelofibrosis secondary to myeloproliferative diseases. American Journal of Hematology, 60, 130-135. doi:10.1002/(SICI)1096-8652(199902)60:2<130::AID-AJH8>3.0.CO;2-Z
[34] Ziakas, P.D., Voulgarelis, M., Felekouras, E., Anagnostou, D. and Tzelepis, G.E. (2005) Myelofibrosis-associated massive splenomegaly: A cause of increased intra-abdominal pressure, pulmonary hypertension, and positional dyspnea. American Journal of Hematology, 80, 128-132. doi:10.1002/ajh.20388
[35] Hadj-Moussa, M. and Brown, J.A. (2010) Reversible renal insufficiency secondary to extrinsic splenic compression of the kidney in a patient with chronic lymphocytic leukemia. Scientific World Journal, 4, 796-798. doi:10.1100/tsw.2010.74
[36] Mistry, P.K., Sadan, S., Yang, R., Yee, J. and Yang, M. (2007) Consequences of diagnostic delays in type 1 Gaucher disease: The need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. American Journal of Hematology, 82, 697-701. doi:10.1002/ajh.20908
[37] Gunay-Aygun, M., Zivony-Elboum, Y., Gumruk, F., Geiger, D., Cetin, M., Khayat, M., Kleta, R., Kfir, N., Anikster, Y., Chezar, J., Arcos-Burgos, M., Shalata, A., Stanescu, H., Manaster, J., Arat, M., Edwards, H., Freiberg, A.S., Hart, P.S., Riney, L.C., Patzel, K., Tanpaiboon, P., Markello, T., Huizing, M., Maric, I., Horne, M., Kehrel, B.E., Jurk, K., Hansen, N.F., Cherukuri, P.F., Jones, M., Cruz, P., Mullikin, J.C., Nurden, A., White, J.G., Gahl, W.A. and Falik-Zaccai, T. (2010) Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. Blood, 116, 4990-5001. doi:10.1182/blood-2010-05-286534
[38] Gunay-Aygun, M., Falik-Zaccai, T.C., Vilboux, T., Zivony-Elboum, Y., Gumruk, F., Cetin, M., Khayat, M., Boerkoel, C.F., Kfir, N., Huang, Y., Maynard, D., Dorward, H., Berger, K., Kleta, R., Anikster, Y., Arat, M., Freiberg, A.S., Kehrel, B.E., Jurk, K., Cruz, P., Mullikin, J.C., White, J.G., Huizing, M. and Gahl, W.A. (2011) NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules. Nature Genetics, 43, 732-734. doi:10.1038/ng.883
[39] Zittoun, J., Zittoun, R., Marquet, J. and Sultan, C. (1975) The three transcobalamins in myeloproliferative disorders and acute leukaemia. British Journal of Haematology, 31, 287-298. doi:10.1111/j.1365-2141.1975.tb00860.x
[40] Rao, V.K. and Oliveira, J.B. (2011) How I treat autoimmune lymphoproliferative syndrome. Blood, 118, 5741-5751. doi:10.1182/blood-2011-07-325217
[41] Takahashi, K., Terashima, K., Kojima, M., Yoshida, H. and Kimura, H. (1977) Pathological, histochemical and ultrastructural studies on sea-blue histiocytes and Gaucher-like cells in acquired lipidosis occurring in leukemia. Acta Pathologica Japonica, 27, 775-797.
[42] Mason, B.A., Bowers, G.R., Guccion, J.G. and Schechter, G.P. (1978) Sea-blue histiocytes in a patient with lymphoma. American Journal of Medicine, 64, 515-518. doi:10.1016/0002-9343(78)90245-0
[43] Lasser, A. (1983) Diffuse histiocytosis of the spleen and idiopathic thrombocytopenic purpura (ITP): Histochemical and ultrastructural studies. American Journal of Clinical Pathology, 80, 529-533.
[44] Hirayama, Y., Kohda, K., Andoh, M., Matsumoto, S., Nakazawa, O., Nobuoka, A., Mochizuki, C., Takayanagi, N. and Ezoe, A. (1996) Syndrome of the sea-blue histiocyte. Internal Medicine Journal, 35, 419-421. doi:10.2169/internalmedicine.35.419
[45] Norum, R.A., Lakier, J.B., Goldstein, S., Angel, A., Goldberg, R.B., Block, W.D., Noffze, D.K., Dolphin, P.J., Edelglass, J., Bogorad, D.D. and Alaupovic, P. (1982) Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. The New England Journal of Medicine, 306, 1513-1519. doi:10.1056/NEJM198206243062503
[46] Sorci-Thomas, M.G. and Thomas, M.J. (2002) The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends in Cardiovascular Medicine, 12, 121-128. doi:10.1016/S1050-1738(01)00163-3
[47] Remaley, A.T., Rust, S., Rosier, M., Knapper, C., Naudin, L., Broccardo, C., Peterson, K.M., Koch, C., Arnould, I., Prades, C., Duverger, N., Funke, H., Assman, G., Dinger, M., Dean, M., Chimini, G., Santamarina-Fojo, S., Fredrickson, D.S., Denefle, P. and Brewer, H.B. Jr. (1999) Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred. Proceedings of the National Academy of Sciences, 96, 12685-12690. doi:10.1073/pnas.96.22.12685
[48] Nguyen, T.T., Kruckeberg, K.E., O’Brien, J.F., Ji, Z.S., Karnes, P.S., Crotty, T.B., Hay, I.D., Mahley, R.W. and O’Brien, T. (2000) Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta 149 Leu)]. The Journal of Clinical Endocrinology & Metabolism, 85, 4354-4358. doi:10.1210/jc.85.11.4354
[49] Naghashpour, M. and Cualing, H. (2009) Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a patient with lecithin-cholesterol acyltransferase deficiency: A clinicopathologic correlation. Metabolism, 58, 1459-1464. doi:10.1016/j.metabol.2009.04.033
[50] Khera, A.V., Cuchel, M., de la Llera-Moya, M., Rodrigues, A., Burke, M.F., Jafri, K., French, B.C., Phillips, J.A., Mucksavage, M.L., Wilensky, R.L., Mohler, E.R., Rothblat, G.H. and Rader, D.J. (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. The New England Journal of Medicine, 364, 127-135 doi:10.1056/NEJMoa1001689.
[51] Savel, J., Lafitte, M., Pucheu, Y., Pradeau, V., Tabarin, A. and Couffinhal, T. (2012) Very low levels of HDL cholesterol and atherosclerosis, a variable relationship—A review of LCAT deficiency. Journal of Vascular Health and Risk Management, 8, 357-361.
[52] Beaudet, A.L., Ferry, G.D., Nichols, B.L. and Rosenberg, H.A. (1977) Cholesterol ester storage disease: Clinical, biochemical, and pathological studies. Pediatrics, 90, 910-914. doi:10.1016/S0022-3476(77)80557-X
[53] Elleder, M., Chlumska, A., Hyanek, J., Poupetova, H., Ledvinova, J., Maas, S. and Lohse, P. (2000) Subclinical course of cholesteryl ester storage disease in an adult with hypercholesterolemia, accelerated atherosclerosis, and liver cancer. Journal of Hepatology, 32, 528-534. doi:10.1016/S0168-8278(00)80407-9
[54] vom Dahl, S., Harzer, K., Rolf, A., Albrecht, B., Niderau, C., Vogt, C., van S. Weely, S., aerts J, Muller, G. and Haussinger, D. (1999) Hepatosplenomegalic lipidosis: What unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, lipodystrophy, increased plasma chitotriosidase activity and homozygous lysosomal acid lipase—2 exon 8 splice junction mutation. Journal of Hepatology, 31, 741-746.
[55] Anderson, R.A., Bryson, G.M. and Parks, J.S. (1999) Lysosomal acid lipase mutations that determine phenotype in Wolman and cholesterol ester storage disease’. Molecular Genetics and Metabolism, 68, 333-345. doi:10.1006/mgme.1999.2904
[56] Tadiboyina VT, Liu DM, Miskie BA, Wang J, Hegele RA. (2005) Treatment of dyslipidemia with lovastatin and ezetimibe in an adolescent with cholesterol ester storage disease. Lipids in Health and Disease. , 4, 26. doi:10.1186/1476-511X-4-26
[57] Hansen, K. and Horslen, S. (2008) Metabolic liver disease in children. Liver Transplantation, 14, 713-733. doi:10.1002/lt.21520
[58] Sévin, M., Lesca, G., Baumann, N., Millat, G., LyonCaen, O., Vanier, M.T. and Sedel, F. (2007) The adult form of Niemann-Pick disease type C. Brain, 130, 120-133.
[59] Zhou, S., Davidson, C., McGlynn, R., Stephney, G., Dobrenis, K., Vanier, M.T. and Walkley, S.U. (2011) Endosomal/lysosomal processing of gangliosides affects neuronal cholesterol sequestration in Niemann-Pick disease type C. American Journal of Pathology, 179, 890-902. doi:10.1016/j.ajpath.2011.04.017
[60] Malnar, M., Kosicek, M., Mitterreiter, S., Omerbasic, D., Lichtenthaler, S.F., Goate, A. and Hecimovic, S. (2010) Niemann-Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the beta-secretase pathway. Biochimica et Biophysica Acta, 1802, 682-691. doi:10.1016/j.bbadis.2010.05.006
[61] Patterson, M.C., Hendriksz, C.J., Walterfang, M., Sedel, F., Vanier, M.T. and Wijburg, F. (2012) On behalf of the NP-C Guidelines Working Group. Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update. Molecular Genetics and Metabolism, 106, 330-344. doi:10.1016/j.ymgme.2012.03.012
[62] Benko, W., Ries, M., Wiggs, E.A., Brady, R.O., Schiffmann, R. and Fitzgibbon, E.J. (2011) The saccadic and neurological deficits in type 3 Gaucher disease. PLoS One, 6, e22410. doi:10.1371/journal.pone.0022410
[63] Wraith, J.E. and Imrie, J. (2009) New therapies in the management of Niemann-Pick type C disease: Clinical utility of miglustat. Journal of Therapeutics and Clinical Risk Management, 5, 877-887. doi:10.2147/TCRM.S5777
[64] Chien, Y.H., Lee, N.C., Tsai, L.K., Huang, A.C., Peng, S.F, Chen, S.J. and Hwu, W.L. (2007) Treatment of Niemann-Pick disease type C in two children with miglustat: Initial responses and maintenance of effects over 1 year. Journal of Inherited Metabolic Disease, 30, 826. doi:10.1007/s10545-007-0630-y
[65] Zarowski, M., Steinborn, B., Gurda, B., Dvorakova, L., Vlaskova, H. and Kothare, S.V. (2011) Treatment of cataplexy in Niemann-Pick disease type C with the use of miglustat. European Journal of Paediatric Neurology, 15, 84-87. doi:10.1016/j.ejpn.2010.02.001
[66] Nietupski, J.B., Pacheco, J.J., Chuang, W.L., Maratea, K., Li, L., Foley, J., Ashe, K.M., Cooper, C.G., Aerts, J.M., Copeland, D.P., Scheule, R.K., Cheng, S.H. and Marshall, J. (2012) Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice. Molecular Genetics and Metabolism, 105, 621-628. doi:10.1016/j.ymgme.2012.01.020
[67] Davidson, C.D., Ali, N.F., Micsenyi, M.C., Stephney, G., Renault, S., Dobrenis, K., Ory, D.S., Vanier, M.T. and Walkley, S.U. (2009) Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS One, 4, e6951. doi:10.1371/journal.pone.0006951
[68] Wasserstein, M.P., Desnick, R.J., Schuchman, E.H., Hossain, S., Wallenstein, S., Lamm, C., McGovern and M.M. (2004) The natural history of type B Niemann-Pick disease: results from a 10-year longitudinal study. Pediatrics, 114, e672-e677. doi:10.1542/peds.2004-0887
[69] McGovern, M.M., Wasserstein, M.P., Giugliani, R., Bembi, B., Vanier, M.T., Mengel, E., Brodie, S.E., Mendelson, D., Skloot, G., Desnick, R.J., Kuriyama, N. and Cox, G.F. (2008) A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. Pediatrics, 122, e341-e349. doi:10.1542/peds.2007-3016
[70] Hollak, C.E., de Sonnaville, E.S., Cassiman, D., Linthorst, G.E., Groener, J.E., Morava, E., Wevers, R.A., Mannens, M., Aerts, J.M., Meersseman, W., Akkerman, E., NiezenKoning, K.E., Mulder, M.F., Visser, G., Wijburg, F.A., Lefeber, D. and Poorthuis, B.J. (2012) Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients. Molecular Genetics and Metabolism, 107, 526-533. doi:10.1016/j.ymgme.2012.06.015
[71] Simpson, W.L. Jr, Mendelson, D., Wasserstein, M.P. and McGovern, M.M. (2010) Imaging manifestations of Niemann-Pick disease type B. AJR American Journal of Roentgenology Diagnostic Imaging and Related Sciences, 194, W12-W19. doi:10.2214/AJR.09.2871
[72] Charrow, J., Andersson, H.C., Kaplan, P., Kolodny, E.H., Mistry, P., Pastores, G., Rosenbloom, B.E., Scott, C.R., Wappner, R.S., Weinreb, N.J. and Zimran, A. (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Archives of Internal Medicine, 160, 2835-2843. doi:10.1001/archinte.160.18.2835
[73] Kaplan, P., Andersson, H.C., Kacena, K.A. and Yee, J.D. (2006) The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Archives of Pediatrics & Adolescent Medicine, 160, 603-608. doi:10.1001/archpedi.160.6.603
[74] Cordeau, M.P., Prosmanne, O. and Robillard, P. (1990) Case of the day. Noncirrhotic idiopathic portal hypertension (Banti syndrome). Radiographics, 10, 114-116.
[75] Vos, B., Moreno, C., Nagy, N., Féry, F., Cnop, M., Vereerstraeten, P., Devière, J. and Adler, M. (2011) Lean non-alcoholic fatty liver disease (Lean-NAFLD): A major cause of cryptogenic liver disease. Acta Gastro-Enterologica Belgica, 74, 389-394.
[76] Emami, M.H., Hashemi, M., Kouhestani, S., Taheri, H. and Karimi, S. (2012) Should we look for celiac disease among all patients with liver function test abnormalities? International Journal of Preventive Medicine, 3, 167-172.
[77] Horai, Y., Miyamura, T., Hirata, A., Nakamura, M., Takahama, S., Ando, H., Minami, R., Yamamoto, M. and Suematsu, E. (2010) Idiopathic portal hypertension in a patient with mixed connective tissue disease and protein C deficiency. Internal Medicine Journal, 49, 2013-2016. doi:10.2169/internalmedicine.49.3834
[78] Castiella, A. (2012) Iron overload and HFE mutations: Are they relevant in cryptogenic cirrhosis? Hepatitis Monthly, 12, 126-127.
[79] Stathakis, N.E., Papayannis, A.G., Dervenoulas, J., Scliros, P. and Gardikas, C. (1974) Multiple coagulation abnormalities in a case of cryptogenic splenomegaly. BMJ, 4, 142-143. doi:10.1136/bmj.4.5937.142
[80] Dacie, J.V., Galton, D.A., Gordon-Smith, E.C. and Harrison, C.V. (1978) Non-tropical idiopathic splenomegaly: A follow-up study of ten patients described in 1969. British Journal of Haematology, 38, 185-193. doi:10.1111/j.1365-2141.1978.tb01035.x
[81] Stahel, R.A., Maurer, R., Cavalli, F. and Fehr, J. (1982) Idiopathic splenomegaly: the preliminary stage of a malignant lymphoma? Report on 2 Cases Schweiz Med Wochenschr, 112, 725-730.
[82] Letoquart, J.P., Casa, C., Grosbois, B., Pompilio, M., Chaperon, J., Lancien, G., Jacomy, D., Leblay, R. and Mambrini, A. (1990) Diagnostic splenectomy. Apropos of 38 Cases Ann Chir, 44, 342-347.
[83] Tantravahi, S.K., Williams, L.B., Digre, K.B., Creel, D.J., Smock, K.J., DeAngelis, M.M., Clayton, F.C., Vitale, A.T. and Rodgers, G.M. (2012) An inherited disorder with splenomegaly, cytopenias, and vision loss. American Journal of Medical Genetics Part A, 158A, 475-481. doi:10.1002/ajmg.a.34437
[84] WHONAMEDIT? (2013) A dictionary of medical eponyms. http://www.whonamedit.com/doctor.cfm/498.html
[85] Gaucher, P.C.E. (1885) De l’epithelioma primitive de las rate, hypertrophie idiopathique de la rate sans leucemie. Academic Thesis, Paris.
[86] Brill, N.E., Mandlebaum, F.S. and Libman, E. (1901) Primary splenomegaly-Gaucher type. Mount Sinai Hospital Reports , 4, 35-48.
[87] Kaplan, P., Baris, H., De Meirleir, L., Di Rocco, M., El-Beshlawy, A., Huemer, M., Martins, A.M., Nascu, I., Rohrbach, M., Steinbach, L. and Cohen, I.J. (2012) Revised recommendations for the management of Gaucher disease in children. European Journal of Pediatrics, July 8. doi:10.1007/s00431-012-1771-z
[88] Rosenbloom, B., Balwani. M., Bronstein, J.M., Kolodny, E., Sathe, S., Gwosdow, A.R., Taylor, J.S., Cole, J.A., Zimran, A. and Weinreb, N.J. (2011) The incidence of Parkinsonism in patients with type 1 Gaucher disease: Data from the ICGG Gaucher Registry. Blood Cells, Molecules and Diseases, 46, 95-102. doi:10.1016/j.bcmd.2010.10.006
[89] Biegstraaten, M., Mengel, E., Marodi, L., Petakov, M., Niederau, C., Giraldo, P., Hughes, D., Mrsic, M., Mehta, A., Hollak, C.E. and van Schaik, I.N. (2010) Peripheral neuropathy in adult type 1 Gaucher disease: A 2-year prospective observational study. Brain, 133, 2009-2919. doi:10.1093/brain/awq198
[90] Grabowski, G.A. (1997) Gaucher disease: Gene frequentcies and genotype/phenotype correlations. Genetic Testing and Molecular Biomarkers, 1, 5-12.
[91] Lachmann, R.H., Grant, I.R., Halsall, D. and Cox, T.M. (2004) Twin pairs showing discordance of phenotype in adult Gaucher’s disease. QJM, 97, 199-204. doi:10.1093/qjmed/hch036
[92] Beutler, E. (1977) Gaucher disease in an asymptomatic 72 year old. JAMA, 237, 2529 doi:10.1001/jama.1977.03270500081038
[93] Allen, M.J., Myer, B.J. Khokher, A.M., Rushton, N. and Cox, T.M. (1997) Pro-inflammatory cytokines and the pathogenesis of Gaucher’s disease: increased release of interleukin-6 and interleukin-10. QJM, 90, 19-25. doi:10.1093/qjmed/90.1.19
[94] Hollak, C.E., Evers, L., Aerts, J.M. and van Oers, M.H. (1997) Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. Blood Cells, Molecules and Diseases, 23, 201-212. doi:10.1006/bcmd.1997.0137
[95] Stein, P., Malhotra, A., Haims, A., Pastores, G.M. and Mistry, P.K. (2010) Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy. Journal of Inherited Metabolic Disease, 33, 769-774. doi:10.1007/s10545-010-9175-6
[96] Mistry, P.K., Liu, J., Yang, M., Nottoli, T., McGrath, J., Jain, D., Zhang, K., Keutzer, J., Chuang, W.L., Mehal, W.Z., Zhao, H., Lin, A., Mane, S., Liu, X., Peng, Y.Z., Li, J.H., Agrawal, M., Zhu, L.L., Blair, H.C., Robinson, L.J., Iqbal, J., Sun, L. and Zaidi, M. (2010) Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proceedings of the National Academy of Sciences, 107, 19473-19478. doi:10.1073/pnas.1003308107
[97] Lecourt, S., Vanneaux, V., Cras, A., Freida, D., Heraoui, D., Herbi, L., Caillaud, C., Chomienne, C., Marolleau, J.P., Belmatoug, N. and Larghero, J. (2012) Bone marrow microenvironment in an in vitro model of Gaucher disease: Consequences of glucocerebrosidase deficiency. Stem Cells and Development, 21, 239-248 doi:10.1089/scd.2011.0365
[98] Rosenbloom, B.E., Kulke, S., Taylor, J. and Weinreb, N.J. (2011) Thrombocytopenia in the absence of splenomegaly in patients with type 1 Gaucher disease: A preliminary analysis from the ICGG Gaucher Registry. Blood, 118, 1802-1803.
[99] Spectre, G., Roth, B., Ronen, G., Rosengarten, D., Elstein, D., Zimran, A., Varon, D. and Revel-Vilk, S. (2011) Platelet adhesion defect in type 1 Gaucher disease is associated with a risk of mucosal bleeding. British Journal of Haematology, 153:372-378. doi:10.1111/j.1365-2141.2011.08613.x
[100] Shitrit, D., Rudensky, B., Zimran, A. and Elstein, D. (2003) D-dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement. American Journal of Hematology, 73, 236-239. doi:10.1002/ajh.10361
[101] Sherif, E.M., Tantawy, A.A., Adly, A.A., Kader, H.A. and Ismail, E.A. (2011) D-dimer assay in Egyptian patients with Gaucher disease: Correlation with bone and lung involvement. Blood Coagul Fibrinolysis, 22, 176-184. doi:10.1097/MBC.0b013e3283424809
[102] Wenstrup, R.J., Roca-Espiau, M., Weinreb, N.J. and Bembi, B. (2002) Skeletal aspects of Gaucher disease: A review. British Journal of Radiology, 75, A2-A12.
[103] Deegan, P.B., Pavlova, E., Tindall, J., Stein, P.E., Bearcroft, P., Mehta, A., Hughes, D., Wraith, J.E. and Cox, T.M. (2011) Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy. Medicine (Baltimore), 90, 52-60. doi:10.1097/MD.0b013e3182057be4
[104] Khan, A., Hangartner, T., Weinreb, N.J., Taylor, J.S. and Mistry, P.K. (2012) Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease—A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry. Journal of Bone and Mineral Research, 27, 1839-1848. doi:10.1002/jbmr.1680
[105] Maas, M., van Kuijk, C., Stoker, J., Hollak, C.E., Akkerman, E.M., Aerts, J.F. and den Heeten, G.J. (2003) Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging—Initial experience. Radiology, 229, 554-561. doi:10.1148/radiol.2292020296
[106] Poll, L.W., vom Dahl, S., Koch, J.A., B?rner, D., Willes, R., Cohnen, M., Jung, G., Scherer, A., Niederau, C., Ha?ssinger, D. and M?dder, U. (2001) Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement. ROFO, 173, 931-937. doi:10.1055/s-2001-17593
[107] Mistry, P.K., Weinreb, N., Kaplan, P., Cole, J.A., Gwosdow, A.R. and Hangartner, T. (2011) Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescents and adults. Blood Cells, Molecules and Diseases, 46, 66-72. doi:10.1016/j.bcmd.2010.10.011
[108] Kaplan, P., Mazur, A., Manor, O., Charrow, J., Esplin, J., Gribble, T.J., Wappner, R.S., Wisch, J.S. and Weinreb, N.J. (1996) Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase. Journal of Pediatrics, 129, 149-153. doi:10.1016/S0022-3476(96)70203-2
[109] Kauli, R., Zaizov, R., Lazar, L., Pertzelan, A., Laron, Z., Galatzer, A., Phillip, M., Yaniv, Y. and Cohen, I.J. (2000) Delayed growth and puberty in patients with Gaucher disease type 1: Natural history and effect of splenectomy and/or enzyme replacement therapy. The Israel Medical Association Journal, 2, 158-163.
[110] Ross, D.J., Spira, S. and Buchbinder, N.A. (1997) Gaucher cells in pulmonary—Capillary blood in association with pulmonary hypertension. The New England Journal of Medicine, 336, 379-381. doi:10.1056/NEJM199701303360516
[111] Kim, J.H., Park, C.H., Pai, M.S., Hahn, M.H. and Kim, H.J. (1999) Hepatopulmonary syndrome in Gaucher disease with right-to-left shunt: evaluation and measurement using Tc-99m MAA. Clinical Nuclear Medicine, 24, 164-166. doi:10.1097/00003072-199903000-00005
[112] Lo, S.M., Liu, J., Chen, F., Pastores, G.M., Knowles, J., Boxer, M., Aleck, K. and Mistry, P.K. (2011) Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long-term outcomes of therapy. Journal of Inherited Metabolic Disease, 34, 643-650.
[113] Anheim, M., Elbaz, A., Lesage, S., Durr, A., Condroyer, C., Viallet, F., Pollak, P., Bona?ti, B., Bona?ti-Pellié, C., Brice, A. (2012) French Parkinson disease genetic group. Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers. Neurology, 78, 417-420. doi:10.1212/WNL.0b013e318245f476
[114] Rosenbloom, B.E., Weinreb, N.J., Zimran, A., Kacena, K.A., Charrow, J. and Ward, E. (2005) Gaucher disease and cancer incidence: a study from the Gaucher registry. Blood, 105, 4569-4572. doi:10.1182/blood-2004-12-4672
[115] de Fost, M., vom Dahl, S., Weverling, G.J., Brill, N., Brett, S., Ha?ssinger, D. and Hollak, C.E. (2006) Increased incidence of cancer in adult Gaucher disease in Western Europe. Blood Cells, Molecules and Diseases, 36, 53-58. doi:10.1016/j.bcmd.2005.08.004
[116] Lo, S.M., Stein, P., Mullaly, S., Bar, M., Jain, D., Pastores, G.M. and Mistry, P.K. (2010) Expanding spectrum of the association between Type 1 Gaucher disease and cancers: a series of patients with up to 3 sequential cancers of multiple types—Correlation with genotype and phenotype. American Journal of Hematology, 85, 340-345.
[117] Choy, F.Y. and Campbell, T.N. (2011) Gaucher disease and cancer: Concept and controversy. International Journal of Cell Biology, 150450.
[118] Weinreb, N.J., Deegan, P., Kacina, K.A., Mistry, P., Pastores, G.M., Velentgas, P. and Vom Dahl, S. (2008) Life expectancy in Gaucher disease type 1. American Journal of Hematology, 83, 896-900. doi:10.1002/ajh.21305
[119] Weinreb, N.J., Barbouth, D. and Lee, R.E. (2011) Causes of death in 184 patients with type 1 Gaucher disease from the United States who were never treated with enzyme replacement therapy. Blood, 118, 1351-3152.
[120] Smid, B.E., Aerts, J.M., Boot, R.G., Linthorst, G.E. and Hollak, C.E. (2010) Pharmacological small molecules for the treatment of lysosomal storage disorders. Expert Opinion on Investigational Drugs, 19, 1367-1379. doi:10.1517/13543784.2010.524205
[121] Lukina, E., Watman, N., Arreguin, E.A., Dragosky, M., Iastrebner, M., Rosenbaum, H., Phillips, M., Pastores, G.M., Kamath, R.S., Rosenthal, D.I., Kaper, M., Singh, T., Puga, A.C. and Peterschmitt, M.J. (2010) Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment—2 years results of a phase 2 study. Blood, 116, 4095-4098. doi:10.1182/blood-2010-06-293902
[122] Weinreb, N.J. and Minsky, N. (1971) Serious Reaction After Konyne. The New England Journal of Medicine, 285, 1151-1152. doi:10.1056/NEJM197111112852027
[123] Weinreb, N.J. (2008) Imiglucerase and its use for the treatment of Gaucher’s disease. Expert Opinion on Pharmacotherapy, 9, 1987-2000. doi:10.1517/14656566.9.11.1987
[124] Andersson, H.C., Kaplan, P., Kacena, K. and Yee, J. (2008) Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics, 122, 1182-1190. doi:10.1542/peds.2007-2144
[125] Weinreb, N.J., Goldblatt, J., Villalobos, J., Charrow, J., Cole, J.A., Kerstenetzky, M., vom Dahl, S. and Hollak, C.E.M. (2012) Long term clinical outcomes in Type 1 Gaucher disease following 10 years of imiglucerase treatment. Journal of Inherited Metabolic Disease. doi:10.1007/s10545-012-9528-4
[126] Webb, B.D., Weinreb, N.J., Botti, A.C., Kirmse, B.M. and Balwani, M. (2011) JAK2V617F mutation and myeloproliferative malignancy in a patient with Type 1 Gaucher disease. Blood Cells, Molecules and Diseases, 46, 103-104. doi:10.1016/j.bcmd.2010.09.007
[127] Srinoun, K., Svasti, S., Chumworathayee, W., Vadolas, J., Vattanaviboon, P., Fucharoen, S. and Winichagoon, P. (2009) Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic mice. Haematologica, 94, 1211-1219. doi:10.3324/haematol.2009.005827
[128] Piga, A., Serra, M., Longo, F., Forni, G., Quarta, G., Cappellini, M.D. and Galanello, R. (2011) Changing patterns of splenectomy in transfusion-dependent thalassemia patients. American Journal of Hematology, 86, 808-810. doi:10.1002/ajh.22102
[129] Moshtaghi-Kashanian, G.R., Gholamhoseinian, A., Hoseinimoghadam, A. and Rajabalian, S. (2006) Splenectomy changes the pattern of cytokine production in beta-thalassemic patients. Cytokine, 35, 253-257. doi:10.1016/j.cyto.2006.09.003
[130] Rodeghiero, F. and Ruggeri, M. (2012) Shortand longterm risks of splenectomy for benign haematological disorders: Should we revisit the indications? British Journal of Haematology, 158, 16-29. doi:10.1111/j.1365-2141.2012.09146.x
[131] Sheikha, A.K., Salih, Z.T., Kasnazan, K.H., Khoshnaw, M.K., Al-Maliki, T., Al-Azraqi, T.A. and Zafer, M.H. (2007) Prevention of overwhelming postsplenectomy infection in thalassemia patients by partial rather than total splenectomy. Canadian Journal of Surgery, 50, 382-386.
[132] Rasekhi, A.R., Naderifar, M., Bagheri, M.H., Shahriari, M., Foroutan, H., Karimi, M. and Nabavizadeh, S.A. (2009) Radiofrequency ablation of the spleen in patients with thalassemia intermedia: a pilot study. AJR American Journal of Roentgenology Diagnostic Imaging and Related Sciences, 192, 1425-1429. doi:10.2214/AJR.08.1382
[133] Perotta, S., Gallagher, P.G. and Mohandas, N. (2008) Hereditary spherocytosis. Lancet, 372, 1411-1426. doi:10.1016/S0140-6736(08)61588-3
[134] Schrier, S.L. (2012) What does the spleen see? Blood, 120, 242-243. doi:10.1182/blood-2012-05-425991
[135] Safeukui, I., Buffet, P.A., Deplaine, G., Perrot, S., Brousse, V., Ndour, A., Nguyen, M., Mercereau-Puijalon, O., David, P.H., Milon, G. and Mohandas, N. (2012) Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen. Blood, 120, 424-430. doi:10.1182/blood-2012-01-404103
[136] Schilling, R.F. (2009) Risks and benefits of splenectomy versus no splenectomy for hereditary spherocytosis—A personal view. British Journal of Haematology, 145, 728-732. doi:10.1111/j.1365-2141.2009.07694.x
[137] Casale, M. and Perrotta, S. (2011) Splenectomy for hereditary spherocytosis: complete, partial, or not at all? Expert Review of Hematology, 4, 627-635. doi:10.1586/ehm.11.51
[138] Crary, S.E., Ramaciotti, C. and Buchanan, G.R. (2011) Prevalence of pulmonary hypertension in hereditary spherocytosis. American Journal of Hematology, 86, E73-E76. doi:10.1002/ajh.22182
[139] Buesing, K.L., Tracy, E.T., Kiernan, C., Pastor. A.C., Cassidy, L.D., Scott, J.P., Ware, R.E., Davidoff, A.M., Rescorla, F.J., Langer, J.C., Rice, H.E. and Oldham, K.T. (2011) Partial splenectomy for hereditary spherocytosis: a multi-institutional review. Journal of Pediatric Surgery, 46, 178-183. doi:10.1016/j.jpedsurg.2010.09.090
[140] Mistry, P.K., Sirrs, S., Chan, A., Pritzker, M.R., Duffy, T.P., Grace, M.E., Meeker, D.P. and Goldman, M.E. (2002) Pulmonary hypertension in type 1 Gaucher’s disease: Genetic and epigenetic determinants of phenotype and response to therapy. Molecular Genetics and Metabolism, 77, 91-98. doi:10.1016/S1096-7192(02)00122-1
[141] Mistry, P.K., Deegan, P., Vellodi, A., Cole, J.A., Yeh, M., Weinreb, N.J. (2009) Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis. British Journal of Haematology, 147, 561-570. doi:10.1111/j.1365-2141.2009.07872.x
[142] Cox, T.M., Aerts. J.M., Belmatoug, N., Cappellini, M.D., vom Dahl, S., Goldblatt, J., Grabowski, G.A., Hollak, C.E., Hwu, P., Maas, M., Martins, A.M., Mistry, P.K., Pastores, G.M., Tylki-Szymanska, A., Yee, J. and Weinreb, N. (2008) Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. Journal of Inherited Metabolic Disease, 31, 319-337. doi:10.1007/s10545-008-0779-z
[143] Okano, K., Kakinoki, K., Suto, H., Oshima, M., Akamoto, S., Hagiike, M., Usuki, H. and Suzuki, Y. (2011) Handassisted laparoscopic partial splenectomy using an endopath monopolar sealer. Surgical Laparoscopy Endoscopy & Percutaneous Techniques, 21, e291-e294. doi:10.1097/SLE.0b013e3182311ee4
[144] Zimran, A., Elstein, D., Schiffmann, R., Abrahamov, A., Goldberg, M., Bar-Maor, J.A., Brady, R.O., Guzzetta, P.C. and Barton, N.W. (1995) Outcome of partial splenectomy for type I Gaucher disease. The Journal of Pediatrics, 126, 596-597. doi:10.1016/S0022-3476(95)70358-6

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