Familial hemophagocytic lymphohistiocytosis type 3 in children: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: Female patient, one year and six months old, with a history of hospitalizations by recurrent febrile conditions, admitted due to pancytopenia, fever, jaundice, hepatosplenomegaly for 8 months. Family history that sister died with a similar condition at 4 months of life. During the hospitalization, the patient presented regression of neuropsychomotor development and ataxy, drowsiness, focal seizures. In two weeks got worse of her neurological condition and the onset of refractory seizures. The patient received therapy with metilprednisolona 30mg/kg/day however, she evolved with hemodynamic, renal, hepatic, hematological and respiratory dysfunction. It progressed to cardiorespiratory arrest and death. Laboratory tests showed: pancytopenia; hyperferritinemia 3000 mcg/L; triglyceride 333 mg/dL, fibrinogen 1,0 g/L. Myelogram showed hemophagocytic. Brain MRI showed multiple areas of signal alteration, areas of cortical rupture, foci of laminar cortical necrosis, and areas of blood-brain barrier breakdown. After all a genetic panel confirmed Familial Hemophagocytic Lymphohistiocytosis type 3 by revealing a mutation in the UNC13D gene: homozygous, variant c.3053C>A (p.Ala1018Asp).

Discussion: fHLH is a rare hyperinflammatory syndrome estimated to affect approximately 1/300,000 newborns in North America. Its primary form is mostly of familial origin, associated with mutations in the PRF1, UNC13D, STX11, and STXBP2 genes, related to lymphocyte cytotoxicity. The diagnosis is based on clinical and laboratory criteria, including persistent fever, splenomegaly, cytopenia, hypertriglyceridemia, and hyperferritinemia. The treatment includes chemotherapy, immunosuppression, and hematopoietic stem cell transplant.

Final Comments: fHLH is a rare and difficult to manage disease that can present similarly to common autoimmune diseases and infections. Despite having diagnostic criteria, genetic panels are of great value in the primary forms of the disease.

Publication History

Article published online:
12 May 2025