Neuronopathic Gaucher disease presenting with microcytic hypochromic anemia

Abstract

Gaucher disease (GD) is caused by a hereditary deficiency of glucocerebrosidase, resulting in accumulation of glucosylceramide and potentially manifesting as hepatosplenomegaly. We report the case of a 15-month-old boy with chronic neuronopathic GD. The patient had prolonged anemia despite continued iron supplementation for 3 months. White blood count (WBC), hemoglobin (Hb), platelet count, and corrected reticulocyte count were 3,300 /µL, 8.7 g/dL, 90,000 /µL, and 0.55, respectively. The patient had microcytic hypochromic anemia with mildly elevated ferritin. Physical examination revealed hepatosplenomegaly. Bone-marrow aspiration showed sheets of Gaucher cells. Glucocerebrosidase activity in monocytes was significantly lower than normal. Genetic analysis revealed a homozygous L444P mutation of GBA, and he was diagnosed with type 1 GD. Enzyme replacement treatment (ERT) consisting of imiglucerase was initiated and was effective; WBC, Hb, and platelet count gradually normalized and the hepatosplenomegaly improved. However, when the patient entered elementary school, he showed mild impaired cognitive function, and supranuclear gaze palsy occurred the same year. He was ultimately diagnosed with type 3 GD and continued ERT. Pediatric hemato-oncologists should be aware of GD, especially when patients exhibit anemia refractory to iron therapy, radiologic bone deformity, neurologic signs or symptoms, and growth retardation.

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Change history

  • 10 January 2019

    In the original publication of this article, Fig. 2 was published incorrectly.

Abbreviations

ERT:

Enzyme replacement treatment

GD:

Gaucher disease

Hb:

Hemoglobin

HSCT:

Hematopoietic stem-cell transplantation

SNP:

Supranuclear gaze palsy

WBC:

White blood count

References

  1. 1.

    Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281:249–54.

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Thomas AS, Mehta A, Hughes DA. Gaucher disease: haematological presentations and complications. Br J Haematol. 2014;165:427–40.

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Thomas AS, Mehta AB, Hughes DA. Diagnosing Gaucher disease: an on-going need for increased awareness amongst haematologists. Blood Cells Mol Dis. 2013;50:212–7.

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    Joo EY, Kim KY, Kim DH, Lee JE, Kim SK. Iron deficiency anemia in infants and toddlers. Blood Res. 2016;51:268–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 5.

    Wang M. Iron deficiency and other types of anemia in infants and children. Am Fam Physician. 2016;93:270–8.

    PubMed  Google Scholar 

  6. 6.

    Lim JY. Iron deficiency anemia in infants and young children. Clin Pediatr Hematol Oncol. 2014;21:47–51.

    Article  Google Scholar 

  7. 7.

    Beutler E. Enzyme replacement in Gaucher disease. PLoS Med. 2004;1:e21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. 8.

    Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of nonneuronopathic gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med. 2006;160:603–8.

    Article  PubMed  Google Scholar 

  9. 9.

    Zimran A, Altarescu G, Rudensky B, Abrahamov A, Elstein D. Survey of hematological aspects of Gaucher disease. Hematology. 2005;10:151–6.

    Article  PubMed  Google Scholar 

  10. 10.

    Orkin SH. Nathan and Oski’s hematology and oncology of infancy and childhood. Philadelphia: Elsevier Saunders; 2015.

    Google Scholar 

  11. 11.

    Tibblin E, Dreborg S, Erikson A, Håkansson G, Svennerholm L. Hematological findings in the Norrbottnian type of Gaucher disease. Eur J Pediatr. 1982;139:187–91.

    Article  PubMed  CAS  Google Scholar 

  12. 12.

    El-Beshlawy A, Tylki-Szymanska A, Vellodi A, Belmatoug N, Grabowski GA, Kolodny EH, et al. Long-term hematological, visceral, and growth outcomes in children with Gaucher disease type 3 treated with imiglucerase in the International Collaborative Gaucher Group Gaucher Registry. Mol Genet Metab. 2017;120:47–56.

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    Benoist DB, McLean E, Egll I, Cogswell M. Worldwide prevalence of anaemia 1993–2005: WHO global database on anaemia: Geneva: World Health Organization. 2008.

    Google Scholar 

  14. 14.

    DeLoughery TG. Microcytic anemia. N Engl J Med. 2014;371:1324–31.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Di Rocco M, Andria G, Deodato F, Giona F, Micalizzi C, Pession A. Early diagnosis of Gaucher disease in pediatric patients: proposal for a diagnostic algorithm. Pediatr Blood Cancer. 2014;61:1905–9.

    Article  PubMed  Google Scholar 

  16. 16.

    Ida H, Rennert OM, Iwasawa K, Kobayashi M, Eto Y. Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation. Hum Genet. 1999;105:120–26.

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Jeong SY, Park SJ, Kim HJ. Clinical and genetic characteristics of Korean patients with Gaucher disease. Blood Cells Mol Dis. 2011;46:11–4.

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Lee JY, Lee BH, Kim GH, Jung CW, Lee J, Choi JH, et al. Clinical and genetic characteristics of Gaucher disease according to phenotypic subgroups. Korean J Pediatr. 2012;55:48–53.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Mistry PK, Sadan S, Yang R, Yee J, Yang M. 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. Am J Hematol. 2007;82:697–701.

    Article  PubMed  Google Scholar 

  20. 20.

    Ito S, Barrett AJ. Gauchers disease–a reappraisal of hematopoietic stem cell transplantation. Pediatr Hematol Oncol. 2013;30:61–70.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the 2015 Yeungnam University Research Grant.

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Correspondence to Jae Min Lee.

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The authors declare that they have no conflict of interest.

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Kim, E.A., Lim, Y.T., Hah, J.O. et al. Neuronopathic Gaucher disease presenting with microcytic hypochromic anemia. Int J Hematol 109, 361–365 (2019). https://doi.org/10.1007/s12185-018-2559-3

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Keywords

  • Gaucher disease
  • Neuronopathic gaucher disease
  • Anemia
  • Enzyme replacement treatment