Acanthocytosis Differential Diagnoses

  • Author: Pedro A de Alarcon, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Nov 30, 2011
 
 

Diagnostic Considerations

Congenital conditions

McLeod red cell phenotype and CGD: The gene that controls Kx expression on RBCs is adjacent to the locus involved in CGD. Large deletions in this region may result in the appearance of both CGD and acanthocytic McLeod red cells. Although most patients with CGD do not have both ailments, those in whom both genes are affected have a mild hemolytic anemia. Large deletions around the XK locus may also cause McLeod syndrome to be accompanied with Duchenne muscular dystrophy, retinitis pigmentosa, and ornithine transcarbamylase deficiency.[6]

Acquired conditions

Echinocytes or Burr cells: Acanthocytes should be distinguished from echinocytes (from the Greek word echinos, which means urchin). These cells appear with multiple small projections that are uniformly distributed on the red cell surface. Echinocytes occur in many conditions, including malnutrition associated with mild hemolysis due to hypomagnesemia and hypophosphatemia, uremia, hemolytic anemia in long-distance runners, and pyruvate kinase deficiency. In vitro, elevated pH, blood storage, ATP depletion, calcium accumulation, and contact with glass can lead to formation of echinocytes.

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Pedro A de Alarcon, MD  William H Albers Professor and Chair, Department of Pediatrics, University of Illinois College of Medicine at Peoria

Pedro A de Alarcon, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Federation for Clinical Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Eastern Society for Pediatric Research, International Society for Experimental Hematology, International Society of Hematology, International Society on Thrombosis and Haemostasis, Medical Society of the State of New York, National Hemophilia Foundation, New York Academy of Sciences, Society for Pediatric Research, Southern Society for Pediatric Research, and Virginia Chapter of the American Academy of Pediatrics and the Virginia Pediatric Society

Disclosure: Nothing to disclose.

Specialty Editor Board

J Martin Johnston, MD  Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

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.

Steven K Bergstrom, MD  Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

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

References

  1. Nasr MB, Symeonidis C, Mikropoulos DG, Kozeis N, Tsinopoulos I, Dimitrakos SA, et al. Disc swelling in abetalipoproteinemia: a novel feature of Bassen-Kornzweig syndrome. Eur J Ophthalmol. Sep-Oct 2011;21(5):674-6. [Medline].

  2. Jung HH, Danek A, Walker RH. Neuroacanthocytosis syndromes. Orphanet J Rare Dis. Oct 25 2011;6:68. [Medline]. [Full Text].

  3. Wimer BM, Marsh WL, Taswell HF, Galey WR. Haematological changes associated with the McLeod phenotype of the Kell blood group system. Br J Haematol. Jun 1977;36(2):219-24. [Medline].

  4. Bertelson CJ, Pogo AO, Chaudhuri A, Marsh WL, Redman CM, Banerjee D, et al. Localization of the McLeod locus (XK) within Xp21 by deletion analysis. Am J Hum Genet. May 1988;42(5):703-11. [Medline]. [Full Text].

  5. Young SG, Bertics SJ, Curtiss LK, Dubois BW, Witztum JL. Genetic analysis of a kindred with familial hypobetalipoproteinemia. Evidence for two separate gene defects: one associated with an abnormal apolipoprotein B species, apolipoprotein B-37; and a second associated with low plasma concentrations of apolipoprotein B-100. J Clin Invest. Jun 1987;79(6):1842-51. [Medline]. [Full Text].

  6. Bassen FA, Kornzweig AL. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood. Apr 1950;5(4):381-87. [Medline].

  7. Branch DR, Gaidulis L, Lazar GS. Human granulocytes lack red cell Kx antigen. Br J Haematol. Apr 1986;62(4):747-55. [Medline].

  8. Azizi E, Zaidman JL, Eshchar J, Szeinberg A. Abetalipoproteinemia treated with parenteral and oral vitamins A and E, and with medium chain triglycerides. Acta Paediatr Scand. Nov 1978;67(6):796-801. [Medline].

  9. Ballas SK, Bator SM, Aubuchon JP, et al. Abnormal membrane physical properties of red cells in McLeod syndrome. Transfusion. Oct 1990;30(8):722-7. [Medline].

  10. Bohlega S, Al-Jishi A, Dobson-Stone C, et al. Chorea-acanthocytosis: clinical and genetic findings in three families from the Arabian peninsula. Mov Disord. Apr 2003;18(4):403-7. [Medline].

  11. Calenda G, Peng J, Redman CM, Sha Q, Wu X, Lee S. Identification of two new members, XPLAC and XTES, of the XK family. Gene. Mar 29 2006;370:6-16. [Medline].

  12. Cooper RA. Anemia with spur cells: a red cell defect acquired in serum and modified in the circulation. J Clin Invest. Oct 1969;48(10):1820-31. [Medline]. [Full Text].

  13. Cooper RA, Diloy Puray M, Lando P, Greenverg MS. An analysis of lipoproteins, bile acids, and red cell membranes associated with target cells and spur cells in patients with liver disease. J Clin Invest. Dec 1972;51(12):3182-92. [Medline]. [Full Text].

  14. Cooper RA, Durocher JR, Leslie MH. Decreased fluidity of red cell membrane lipids in abetalipoproteinemia. J Clin Invest. Jul 1977;60(1):115-21. [Medline]. [Full Text].

  15. Cooper RA, Gulbrandsen CL. The relationship between serum lipoproteins and red cell membranes in abetalipoproteinemia: deficiency of lecithin:cholesterol acyltransferase. J Lab Clin Med. Sep 1971;78(3):323-35. [Medline].

  16. Cooper RA, Kimball DB, Durocher JR. Role of the spleen in membrane conditioning and hemolysis of spur cells in liver disease. N Engl J Med. Jun 6 1974;290(23):1279-84. [Medline].

  17. Danek A, Jung HH, Melone MA, et al. Neuroacanthocytosis: new developments in a neglected group of dementing disorders. J Neurol Sci. Mar 15 2005;229-230:171-86. [Medline].

  18. Danek A, Rubio JP, Rampoldi L, et al. McLeod neuroacanthocytosis: genotype and phenotype. Ann Neurol. Dec 2001;50(6):755-64. [Medline].

  19. Danks DM, Campbell PE, Smith AL, Rogers J. Prognosis of babies with neonatal hepatitis. Arch Dis Child. May 1977;52(5):368-72. [Medline]. [Full Text].

  20. Dobson-Stone C, Danek A, Rampoldi L, et al. Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis. Eur J Hum Genet. Nov 2002;10(11):773-81. [Medline].

  21. Dobson-Stone C, Velayos-Baeza A, Jansen A, et al. Identification of a VPS13A founder mutation in French Canadian families with chorea-acanthocytosis. Neurogenetics. Sep 2005;6(3):151-8. [Medline].

  22. Dodge JT, Cohen G, Kayden HJ, Phillips GB. Peroxidative hemolysis of red blood cells from patients with abetalipoproteinemia (acanthocytosis). J Clin Invest. Mar 1967;46(3):357-68. [Medline]. [Full Text].

  23. Estes JW, Morley TJ, Levine IM, Emerson CP. A new hereditary acanthocytosis syndrome. Am J Med. Jun 1967;42(6):868-81. [Medline].

  24. Forsyth CC, Lloyd JK, Fosbrooke AS. A-beta-lipoproteinaemia. Arch Dis Child. Feb 1965;40:47-51. [Medline]. [Full Text].

  25. Gracey M, Hilton HB. Acanthocytes and hypobetailipoproteinemia. Lancet. Mar 24 1973;1(7804):679. [Medline].

  26. Henkel K, Danek A, Grafman J, Butman J, Kassubek J. Head of the caudate nucleus is most vulnerable in chorea-acanthocytosis: a voxel-based morphometry study. Mov Disord. Oct 2006;21(10):1728-31. [Medline].

  27. Higgins JJ, Patterson MC, Papadopoulos NM, et al. Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome). Neurology. Jan 1992;42(1):194-8. [Medline].

  28. Illingworth DR, Connor WE, Miller RG. Abetalipoproteinemia. Report of two cases and review of therapy. Arch Neurol. Oct 1980;37(10):659-62. [Medline].

  29. Jandl JH. The anemia of liver disease: observations on its mechanism. J Clin Invest. Mar 1955;34(3):390-404. [Medline].

  30. Kapff CT, Jandl JH. Acanthocytes. Spur cells. Burr cells. In: Blood: Atlas and Sourcebook of Hematology. 2nd ed. Baltimore, MD: Lippincott, Williams & Wilkins; 1991:46.

  31. Keimowitz R, Desforges JF. Infantile pyknocytosis. N Engl J Med. Nov 18 1965;273(21):1152-4. [Medline].

  32. Lange Y, Steck TL. Mechanism of red blood cell acanthocytosis and echinocytosis in vivo. J Membr Biol. 1984;77(2):153-9. [Medline].

  33. Lee S, Zambas ED, Marsh WL, Redman CM. Molecular cloning and primary structure of Kell blood group protein. Proc Natl Acad Sci U S A. Jul 15 1991;88(14):6353-7. [Medline]. [Full Text].

  34. Levy RI, Fredrickson DS, Laster L. The lipoproteins and lipid transport in abetalipoproteinemia. J Clin Invest. Apr 1966;45(4):531-41. [Medline]. [Full Text].

  35. Mant MJ, Faragher BS. The haematology of anorexia nervosa. Br J Haematol. Dec 1972;23(6):737-49. [Medline].

  36. Marsh WL. The Kell blood group, Kx antigen, and chronic granulomatous disease. Mayo Clin Proc. Mar 1977;52(3):150-2. [Medline].

  37. Marsh WL, Uretsky SC, Douglas SD. Antigens of the Kell blood group system on neutrophils and monocytes: their relation to chronic granulomatous disease. J Pediatr. Dec 1975;87(6 PT 2):1117-20. [Medline].

  38. McBride JA, Jacob HS. Abnormal kinetics of red cell membrane cholesterol in acanthocytes: studies in genetic and experimental abetalipoproteinaemia and in spur cell anaemia. Br J Haematol. Apr 1970;18(4):383-97. [Medline].

  39. Muller-Vahl KR, Berding G, Emrich HM, Peschel T. Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging, FDG-PET and (123)I-beta-CIT-SPECT. J Neurol. Aug 2007;254(8):1081-8. [Medline].

  40. Neerhout RC. Red cell lipids in hypothyroidism. Clin Chim Acta. Oct 1972;41:347-53. [Medline].

  41. Owen JS, Brown DJ, Harry DS, McIntyre N, Beaven GH, Isenberg H, et al. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins. J Clin Invest. Dec 1985;76(6):2275-85. [Medline]. [Full Text].

  42. Peng J, Redman CM, Wu X, Song X, Walker RH, Westhoff CM. Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases. Gene. May 1 2007;392(1-2):142-50. [Medline].

  43. Rader DJ, Brewer HB. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA. Aug 18 1993;270(7):865-9. [Medline].

  44. Rampoldi L, Dobson-Stone C, Rubio JP, et al. A conserved sorting-associated protein is mutant in chorea-acanthocytosis. Nat Genet. Jun 2001;28(2):119-20. [Medline].

  45. Robertson AL. Acanthocytes and hypobetalipoproteinaemia. Lancet. Apr 21 1973;1(7808):882. [Medline].

  46. Rubio JP, Danek A, Stone C, Chalmers R, Wood N, Verellen C, et al. Chorea-acanthocytosis: genetic linkage to chromosome 9q21. Am J Hum Genet. Oct 1997;61(4):899-908. [Medline]. [Full Text].

  47. Saiki S, Sakai K, Murata KY, Saiki M, Nakanishi M, Kitagawa Y. Primary skeletal muscle involvement in chorea-acanthocytosis. Mov Disord. Apr 30 2007;22(6):848-52. [Medline].

  48. Salt HB, Wolff OH, Lloyd JK, et al. On having no beta-lipoprotein. A syndrome comprising a-beta-lipoproteinaemia, acanthocytosis, and steatorrhoea. Lancet. Aug 13 1960;2:325-9. [Medline].

  49. Sharp D, Blinderman L, Combs KA, et al. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature. Sep 2 1993;365(6441):65-9. [Medline].

  50. Shinitzky M, Barenholz Y. Dynamics of the hydrocarbon layer in liposomes of lecithin and sphingomyelin containing dicetylphosphate. J Biol Chem. Apr 25 1974;249(8):2652-7. [Medline].

  51. Silber R, Amorosi E, Lhowe J, Kayden HJ. Spur-shaped erythrocytes in Laennec's cirrhosis. N Engl J Med. Sep 22 1966;275(12):639-43. [Medline].

  52. Smith JA, Lonergan ET, Sterling K. Spur-cell anemia: hemolytic anemia with red cells resembling acanthocytes in alcoholic cirrhosis. N Engl J Med. Aug 20 1964;271:396-8. [Medline].

  53. Spencer SE, Walker FO, Moore SA. Chorea-amyotrophy with chronic hemolytic anemia: a variant of chorea-amyotrophy with acanthocytosis. Neurology. Apr 1987;37(4):645-9. [Medline].

  54. Sperling MA, Hengstenberg F, Yunis E. Abetalipoproteinemia: metabolic, endocrine, and electron-microscopic investigations. Pediatrics. Jul 1971;48(1):91-102. [Medline].

  55. Suarez L, Valbuena ML, Moreno A, et al. Abetalipoproteinemia associated with hepatic and atypical neurological disorders. J Pediatr Gastroenterol Nutr. Sep-Oct 1987;6(5):799-802. [Medline].

  56. Symmans WA, Shepherd CS, Marsh WL, et al. Hereditary acanthocytosis associated with the McLeod phenotype of the Kell blood group system. Br J Haematol. Aug 1979;42(4):575-83. [Medline].

  57. Takeshita J, Arai Y, Hirose N, et al. Abetalipoproteinemia-like lipid profile and acanthocytosis in a young woman with anorexia nervosa. Am J Med Sci. Nov 2002;324(5):281-4. [Medline].

  58. Tarugi P, Averna M, Di Leo E, Cefalù AB, Noto D, Magnolo L. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis. Dec 2007;195(2):e19-27. [Medline].

  59. Taswell HF, Lewis JC, Marsh WL, et al. Erythrocyte morphology in genetic defects of the Rh and Kell blood group systems. Mayo Clin Proc. Mar 1977;52(3):157-9. [Medline].

  60. Terada N, Fujii Y, Ueda H, et al. Ultrastructural changes of erythrocyte membrane skeletons in chorea-acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep-etching method. Acta Haematol. Mar 1999;101(1):25-31. [Medline].

  61. Udden MM, Umeda M, Hirano Y, Marcus DM. New abnormalities in the morphology, cell surface receptors, and electrolyte metabolism of In(Lu) erythrocytes. Blood. Jan 1987;69(1):52-7. [Medline].

  62. Ueno S, Maruki Y, Nakamura M, et al. The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nat Genet. 2001;28:121-122. [Medline].

  63. Velayos-Baeza A, Vettori A, Copley RR, et al. Analysis of the human VPS13 gene family. Genomics. Sep 2004;84(3):536-49. [Medline].

  64. Wardrop CA, Hutchison HE. Red cell shape in hypothyroidism. J Clin Pathol. May 1970;23(4):377. [Medline]. [Full Text].

  65. Wetterau JR, Aggerbeck LP, Bouma ME, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. Nov 6 1992;258(5084):999-1001. [Medline].

 
Previous
Next
 
This image (magnified X 2000) shows the spiculated thorny RBCs (acanthocytes) as observed in an individual with abetalipoproteinemia. These are indistinguishable from the acanthocytes shown in the next image, which are observed in an individual with spur cell hemolytic anemia. Used with permission from Little, Brown and Company.
This image (magnified X 2000) demonstrates acanthocytes in an individual with spur cell hemolytic anemia associated with alcoholic cirrhosis. Acanthocytes, unlike echinocytes or burr cells, have fewer spicules. Used with permission from Little, Brown and Company.
This image (magnified X 2000) shows echinocytes, or burr cells, a universal feature of uremia. The spicules of acanthocytes vary in length and width and project nonuniformly from the cell surface, while burr cells have regularly spaced, smoothly rounded crenulations. The second morphologic feature of RBCs in an individual with uremia is the presence of ellipsoid cells. Used with permission from Little, Brown and Company.
 
 
 
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.