Kidney Malformation and Persistent Neutropenia

  • Mihaela Tatiana Bataneant


Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome is characterized by warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis. Absence of myelokathexis excludes the diagnosis

An important diagnostic features of the neutropenia of WHIM syndrome is the elevation of neutrophil count during infections and a rapid response to low doses of granulocyte colony stimulating factor (G-CSF)

Prognosis for WHIM depends in part on early recognition of the disorder, with aggressive medical intervention to reduce the frequency of recurrent bacterial infections and to detect and extirpate early HPV lesions that appear to be dysplastic or malignant


Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis Granulocyte colony stimulating factor WHIM 


  1. 1.
    Segel GB, Halterman JS. Neutropenia in pediatric practice. Pediatr Rev. 2008;29(1):12–23.CrossRefGoogle Scholar
  2. 2.
    Berliner N, Horwitz M, Loughran TP Jr. Congenital and acquired neutropenia. Hematology Am Soc Hematol Educ Program. 2004:63–79.Google Scholar
  3. 3.
    Dufour C, Miano M, Fioredda F. Old and new faces of neutropenia in children. Haematologica. 2016;101(7):789–91.CrossRefGoogle Scholar
  4. 4.
    Wetzler M, Talpaz M, Kleinerman ES, King A, Huh YO, Gutterman JU, Kurzrock R. A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. Am J Med. 1990;89:663–72.CrossRefGoogle Scholar
  5. 5.
    Diaz GA, Gulino AV. WHIM syndrome: a defect in CXCR4 signaling. Curr Allergy Asthma Rep. 2005;5(5):350–5.CrossRefGoogle Scholar
  6. 6.
    Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR Jr. WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet. 2005;91(5):368–76.CrossRefGoogle Scholar
  7. 7.
    Gulino AV, Moratto D, Sozzani S, Cavadini P, Otero K, Tassone L, Imberti L, Pirovano S, Notarangelo LD, Soresina R, Mazzolari E, Nelson DL, Notarangelo LD, Badolato R. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood. 2004;104(2):444–52.CrossRefGoogle Scholar
  8. 8.
    Gulino AV. WHIM syndrome: a genetic disorder of leukocyte trafficking. Curr Opin Allergy Clin Immunol. 2003;3(6):443–50.CrossRefGoogle Scholar
  9. 9.
    Hess U, Ganser A, Schnürch HG, Seipelt G, Ottmann OG, Falk S, Schulz G, Hoelzer D. Myelokathexis treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Br J Haematol. 1992;80(2):254–6.CrossRefGoogle Scholar
  10. 10.
    Aprikyan AA, Liles WC, Park JR, Jonas M, Chi EY, Dale DC. Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors. Blood. 2000;95(1):320–7.Google Scholar
  11. 11.
    Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, Lebbe C, Kerob D, Dupuy A, Hermine O, Nicolas JF, Latger-Cannard V, Bensoussan D, Bordigoni P, Baleux F, Le Deist F, Virelizier JL, Arenzana-Seisdedos F, Bachelerie F. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood. 2005;105(6):2449–57.CrossRefGoogle Scholar
  12. 12.
    Tarzi M, Jenner M, Hattotuwa K, Faruqi AZ, Diaz GA, Longhurst HJ. Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome. J Allergy Clin Immunol. 2005;116(5):1101–5.CrossRefGoogle Scholar
  13. 13.
    Arai J, Wakiguchi H, Hisakawa H, Kubota H, Kurashige T. A variant of myelokathexis with hypogammaglobulinemia: lymphocytes as well as neutrophils may reverse in response to infections. Pediatr Hematol Oncol. 2000;17(2):171–6.CrossRefGoogle Scholar
  14. 14.
    Imashuku S, Miyagawa A, Chiyonobu T, Ishida H, Yoshihara T, Teramura T, Kuriyama K, Imamura T, Hibi S, Morimoto A, Todo S. Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic syndrome, followed by fatal intestinal B lymphoma in a young adult female with WHIM syndrome. Ann Hematol. 2000;81(8):470–3.CrossRefGoogle Scholar
  15. 15.
    Taniuchi S, Yamamoto A, Fujiwara T, Hasui M, Tsuji S, Kobayashi Y. Dizygotic twin sisters with myelokathexis: mechanism of its neutropenia. Am J Hematol. 1999;62(2):106–11.CrossRefGoogle Scholar
  16. 16.
    Takaya J, Fujii Y, Higashino H, Taniuchi S, Nakamura M, Kaneko K. A case of WHIM syndrome associated with diabetes and hypothyroidism. Pediatr Diabetes. 2009;10:484–6.CrossRefGoogle Scholar
  17. 17.
    Tassone L, Notarangelo LD, Bonomi V, Savoldi G, Sensi A, Soresina A, Smith CI, Porta F, Plebani A, Notarangelo LD, Badolato R. Clinical and genetic diagnosis of س صزثwarts, hypogammaglobulinemia, infections, and myelokathexis syndrome in 10 patients. J Allergy Clin Immunol. 2009;123(5):1170–3.CrossRefGoogle Scholar
  18. 18.
    Plebani A, Cantù-Rajnoldi A, Collo G, Allavena P, Biolchini A, Pirelli A, Clerici Schoeller M, Masarone M. Myelokathexis associated with multiple congenital malformations: immunological study on phagocytic cells and lymphocytes. Eur J Haematol. 1988;40(1):12–7.CrossRefGoogle Scholar
  19. 19.
    Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A. 1988;95(16):9448–53.CrossRefGoogle Scholar
  20. 20.
    Ueland J, Yuan A, Marlier A, Gallagher AR, Karihaloo A. A novel role for the chemokine receptor Cxcr4 in kidney morphogenesis: an in vitro study. Dev Dyn. 2009;238(5):1083–91.CrossRefGoogle Scholar
  21. 21.
    Yuan A, Lee Y, Choi U, Moeckel G, Karihaloo A. Chemokine receptor Cxcr4 contributes to kidney fibrosis via multiple effectors. Am J Physiol Renal Physiol. 2015;308(5):F459–72.CrossRefGoogle Scholar
  22. 22.
    Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol. 1999;17:657.CrossRefGoogle Scholar
  23. 23.
    Kawai T, Malech HL. WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol. 2009;16(1):20–6.CrossRefGoogle Scholar
  24. 24.
    Weston B, Axtell RA, Todd RF 3rd, Vincent M, Balazovich KJ, Suchard SJ, Boxer LA. Clinical and biologic effects of granulocyte colony stimulating factor in the treatment of myelokathexis. J Pediatr. 1991;118(2):229–34.CrossRefGoogle Scholar
  25. 25.
    Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N, Sandbank J, Zipori D, Lapidot T. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3(7):687–94.CrossRefGoogle Scholar
  26. 26.
    Goddard EA, Hughes EJ, Beatty DW. A case of immunodeficiency characterized by neutropenia, hypogammaglobulinaemia, recurrent infections and warts. Clin Lab Haematol. 1994;16(3):297–302.CrossRefGoogle Scholar
  27. 27.
    Hord JD, Whitlock JA, Gay JC, Lukens JN. Clinical features of myelokathexis and treatment with hematopoietic cytokines: a case report of two patients and review of the literature. J Pediatr Hematol Oncol. 1997;19(5):443–8.CrossRefGoogle Scholar
  28. 28.
    Vinurel H, Freymond N, Pacheco Y, Devouassoux G. The Whim syndrome: a rare cause of diffuse bronchiectasis. Immune defect of CXCR4 and chronic bronchial suppuration. Rev Mal Respir. 2008;25(5):614–8.CrossRefGoogle Scholar
  29. 29.
    Chae KM, Ertle JO, Tharp MD. B-cell lymphoma in a patient with WHIM syndrome. J Am Acad Dermatol. 2001;44(1):124–8.CrossRefGoogle Scholar
  30. 30.
    Kriván G, Erdos M, Kállay K, Benyó G, Tóth A, Sinkó J, Goda V, Tóth B, Maródi L. Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome. Eur J Haematol. 2010;84(3):274–5.CrossRefGoogle Scholar
  31. 31.
    Bhar S, Yassine K, Martinez C, Sasa GS, Naik S, Mahoney D Jr, Allen C, Ahmed N, Hegde MG, Heslop HE, Gottschalk S, Krance RA, Leung KS. Allogeneic stem cell transplantation in a pediatric patient with Whim syndrome. Blood. 2015;126:5528.Google Scholar
  32. 32.
    Moens L, Frans G, Bosch B, Bossuyt X, Verbinnen B, Poppe W, Boeckx N, Slatter M, Brusselmans C, Diaz G, Tousseyn T, Flipts H, Corveleyn A, Dierickx D, Meyts I. Successful hematopoietic stem cell transplantation for myelofibrosis in an adult with warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome. J Allergy Clin Immunol. 2016;138(5):1485–9.CrossRefGoogle Scholar
  33. 33.
    Dale DC, Bolyard AA, Kelley ML, Westrup EC, Makaryan V, Aprikyan A, Wood B, Hsu FJ. The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. Blood. 2011;118(18):4963–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mihaela Tatiana Bataneant
    • 1
    • 2
  1. 1.“Victor Babes” University of Medicine and PharmacyTimisoaraRomania
  2. 2.“Louis Turcanu” Children’s Emergency Clinical HospitalTimisoaraRomania

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