Wolman's disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review

BMC Pediatr. 2021 Feb 10;21(1):72. doi: 10.1186/s12887-021-02541-2.


Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome that is characterized by strong activation of the immune system from hyperinflammatory cytokines. Symptoms of HLH patients include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. Inherited HLH is classified as primary, whereas secondary HLH (sHLH) occurs when acquired from non-inherited reasons that include severe infection, immune deficiency syndrome, autoimmune disorder, neoplasm, and metabolic disorder. Wolman's disease (WD) is a rare and fatal infantile metabolic disorder caused by lysosomal acid lipase deficiency, that exhibits similar clinical signs and symptoms as HLH. This paper reports the case of an infant diagnosed with WD and who presented with sHLH.

Case presentation: A 4-month-old infant presenting with hepatosplenomegaly, failure to thrive, and other abnormalities. WD diagnosis was confirmed by the presence of the LIPA gene homozygous deletion c.(428 + 1_967-1)_(*1_?)del. The infant also met the HLH-2004 diagnostic criteria.

Conclusions: Metabolic disorder such as WD should be investigated in infants fulfilling the HLH criteria to diagnose the underlying condition. More studies are needed to understand the link between WD and sHLH and to identify appropriate therapies.

Keywords: Hemophagocytic lymphohistiocytosis; Lipid storage disorder; Lysosomal acid lipase; Wolman’s disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Homozygote
  • Humans
  • Infant
  • Lymphohistiocytosis, Hemophagocytic* / etiology
  • Lymphohistiocytosis, Hemophagocytic* / genetics
  • Saudi Arabia
  • Sequence Deletion
  • Wolman Disease* / complications
  • Wolman Disease* / diagnosis
  • Wolman Disease* / genetics