Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
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Variants of LYST and Novel STK4 Gene Mutation in a Child With Accelerated Chediak Higashi Syndrome

  • Received : 2024.01.15
  • Accepted : 2024.03.02
  • Published : 2024.04.25
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Abstract

Chediak-Higashi syndrome (CHS) is a rare haematological and immunodeficiency disorder that occurs in childhood leading to recurrent infections, bleeding tendencies and progressive neurological dysfunction. Partial oculocutaneous albinism occurs in almost all cases. The exact prevalence is unknown, and the disease is caused by over 70 identified mutations in the lysosomal trafficking regulator gene. The presence of a bright polychromatic appearance from hair shaft and abnormally large intracytoplasmic granules, especially within neutrophils and platelets in the bone marrow is highly suggestive. Treatment is largely supportive, and the only curative treatment is through an allogeneic hematopoietic stem cell transplant. Without transplant, most patients will enter an accelerated phase of hemophagocytic lymphohistiocytosis (HLH) which carries a high mortality rate. We present a young male with CHS who we had followed through and eventually developed a fulminant accelerated phase. We believe this is only the second reported case of CHS in Malaysia.

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Acknowledgement

Clinical practitioners who have provided the necessary investigative and imaging reports used in this manuscript. We declare no funding or financial support in the production of this manuscript.

References

  1. Arulappan J, Thomas DS, Wali YA, Jayapal SK, Venkatasalu MR. A child with Chediak-Higashi syndrome-a case study. Curr Pediatr Res 2018;22:69-72. 
  2. Jayaranee S, Menaka N. Chediak-Higashi syndrome: a case report. Malays J Pathol 2004;26:53-7.
  3. Sharma P, Nicoli ER, Serra-Vinardell J, Morimoto M, Toro C, Malicdan MCV, et al. Chediak-Higashi syndrome: a review of the past, present, and future. Drug Discov Today Dis Models 2020;31:31-6. https://doi.org/10.1016/j.ddmod.2019.10.008
  4. Siddiqui E, Hanif S. Chediak-Higashi syndrome. Pak J Med Sci 2008;24:328-30. 
  5. Helmi MM, Saleh M, Yacop B, ElSawy D. Chediak-Higashi syndrome with novel gene mutation. BMJ Case Rep 2017;2017:bcr2016216628.
  6. Patne SC, Kumar S, Bagri NK, Kumar A, Shukla J. Chediak-higashi syndrome: a case report. Indian J Hematol Blood Transfus 2013;29:80-3.  https://doi.org/10.1007/s12288-011-0130-y
  7. Valente NY, Machado MC, Boggio P, Alves AC, Bergonse FN, Casella E, et al. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo) 2006;61:327-32. https://doi.org/10.1590/S1807-59322006000400009
  8. Morimoto M, Nicoli ER, Kuptanon C, Roney JC, Serra-Vinardell J, Sharma P, et al. Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature. J Med Genet 2024;61:212-23.
  9. Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer AA, et al. The phenotype of human STK4 deficiency. Blood 2012;119:3450-7. https://doi.org/10.1182/blood-2011-09-378158
  10. Nehme NT, Schmid JP, Debeurme F, Andre-Schmutz I, Lim A, Nitschke P, et al. MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. Blood 2012;119:3458-68. https://doi.org/10.1182/blood-2011-09-378364
  11. Upton J. Immunodeficiencies with hypergammaglobulinemia: a review. LymphoSign Journal. 2014;2:150113084544003.
  12. Boxer LA, Watanabe AM, Rister M, Besch HR Jr, Allen J, Baehner RL. Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. N Engl J Med 1976;295:1041-5. https://doi.org/10.1056/NEJM197611042951904
  13. Lozano ML, Rivera J, Sanchez-Guiu I, Vicente V. Towards the targeted management of Chediak-Higashi syndrome. Orphanet J Rare Dis 2014;9:132.
  14. Aslan Y, Erduran E, Gedik Y, Mocan H, Yildiran A. The role of high dose methylprednisolone and splenectomy in the accelerated phase of Chediak-Higashi syndrome. Acta Haematol 1996;96:105-7. https://doi.org/10.1159/000203725
  15. Sparber-Sauer M, Honig M, Schulz AS, zur Stadt U, Schutz C, Debatin KM, et al. Patients with early relapse of primary hemophagocytic syndromes or with persistent CNS involvement may benefit from immediate hematopoietic stem cell transplantation. Bone Marrow Transplant 2009;44:333-8. https://doi.org/10.1038/bmt.2009.34
  16. Tardieu M, Lacroix C, Neven B, Bordigoni P, de Saint Basile G, Blanche S, et al. Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome. Blood 2005;106:40-2.
  17. Eapen M, DeLaat CA, Baker KS, Cairo MS, Cowan MJ, Kurtzberg J, et al. Hematopoietic cell transplantation for Chediak-Higashi syndrome. Bone Marrow Transplant 2007;39:411-5. https://doi.org/10.1038/sj.bmt.1705600
  18. Sung JH, Meyers JP, Stadlan EM, Cowen D, Wolf A. Neuropathological changes in Chediak-Higashi disease. J Neuropathol Exp Neurol 1969;28:86-118. https://doi.org/10.1097/00005072-196901000-00005