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European Journal of Pediatrics

, Volume 173, Issue 10, pp 1391–1394 | Cite as

Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation

  • Roberta Taurisano
  • Arianna Maiorana
  • Fabrizio De Benedetti
  • Carlo Dionisi-Vici
  • Renata Boldrini
  • Federica DeodatoEmail author
Short Communication

Abstract

The lysosomal acid lipase (LAL) is the enzyme responsible of the hydrolysis of cholesteryl esters and triglycerides within endo-lysosomes. Loss of enzyme activity leads to accumulation of cholesteryl esters and triglycerides in the lysosome of most tissues. The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition which may be genetically determined or secondary to infections, malignancies, immune deficiencies, and rheumatologic disorders. So far, some inborn errors of metabolism have been associated with HLH (e.g., lysinuric protein intolerance, Gaucher’s disease), and it has been anecdotally described in three WD patients, without any specific pathogenetic hypothesis. Here, we report on a WD patient, showing clear clinical, biochemical, and histological features indicative of HLH. We discuss the pathophysiological role of cholesteryl ester-induced inflammasome activation in macrophages, leading to a secondary HLH. Conclusion: This case indicates that WD can cause secondary HLH and suggests that a careful metabolic workup should be performed when facing to a pediatric patient with HLH.

Keywords

Wolman disease Hemophagocytic lymphohistiocytosis Cholesterol crystal Inflammasome 

Notes

Conflict of interest

No conflicts of interest exist for any of the authors.

Funding

Any authors have not received financial support for this study.

References

  1. 1.
    Al Essa M, Nounou R, Sakati N, Le Quesne G, Joshi S, Archibald A, Ozan PT (1998) Wolman’s disease: the King Faisal Specialist Hospital and Research Centre experience. Ann Saudi Med 18:120–124PubMedGoogle Scholar
  2. 2.
    Boldrini R, Devito R, Biselli R, Filocamo M, Bosman C (2004) Wolman disease and cholesteryl ester storage disease diagnosed by histological and ultrastructural examination of intestinal and liver biopsy. Pathol Res Pract 200:231–240PubMedCrossRefGoogle Scholar
  3. 3.
    Duval M, Fennetau O, Doireai V, Faye A, Emilie D, Yotnda P, Drapier JC, Schlegel N, Sterkers G, deBaulny HO, Vilmer E (1999) Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr 134:236–239PubMedCrossRefGoogle Scholar
  4. 4.
    Gokce M, Unal O, Hismi B, Gumruk F, Coskun T, Balta G, Unal S, Cetin M, Kalkanoglu-Sivri HS, Dursun A, Tokatli A (2012) Secondary hemophagocytosis in 3 patients with organic academia involving propionate metabolism. Pediatr Hematol Oncol 29:92–98PubMedCrossRefGoogle Scholar
  5. 5.
    Henter JI, Horne A, Aricò M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G (2007) HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131PubMedCrossRefGoogle Scholar
  6. 6.
    Kundak AA, Zenciroglu A, Yarali N, Karagol BS, Dursun A, Gokce S, Karadag N, Okumus N (2012) An unusual presentation of galactosemia: hemophagocytic lymphohistiocytosis. Turk J Hematol 29:401–404CrossRefGoogle Scholar
  7. 7.
    Perry R, Kecha O, Paquette J, Huot C, Van Vliet G, Deal C (2005) Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab 90:3243–3250PubMedCrossRefGoogle Scholar
  8. 8.
    Rajamäki K, Lappalainen J, Oörni K, Välimäki E, Matikainen S, Kovanen PT, Eklund KK (2010) Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One 5(7):e11765PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y (2013) The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med 11:185PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Wu S, Gonzalez-Gomez I, Coates T, Yano S (2005) Cobalamin C disease presenting with hemophagocytic lymphohistiocytosis. Pediatr Hematol Oncol 22:717–721PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Roberta Taurisano
    • 1
  • Arianna Maiorana
    • 1
  • Fabrizio De Benedetti
    • 2
  • Carlo Dionisi-Vici
    • 1
  • Renata Boldrini
    • 3
  • Federica Deodato
    • 1
    Email author
  1. 1.Division of Metabolism, Department of Pediatric Medicine, Bambino Gesu’ Children’s HospitalIRCCSRomeItaly
  2. 2.Division of Rheumatology, Department of Pediatric MedicineIRCCSRomeItaly
  3. 3.Pathology Unit, Bambino Gesu’ Children’s HospitalIRCCSRomeItaly

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