title: Familial hemophagocytic lymphohistiocytosis in a 6-week-old male infant.
abstract: Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessively inherited multisystem disease. This defect in cellular cytotoxicity is a life threatening condition characterized by fever, rash, splenomegaly, cytopenias and neurologic manifestations. PRF1, UNC13D and STX11 gene defects underlie in about 40-50% of primary cases. Chemoimmunotherapy followed by hematopoietic stem cell transplantation improved disease outcome. We report a case of a 6-week-old boy who presented with a fever, diffuse rash, disseminated intravascular coagulation, hypofibrinogenemia, hypertrigliceridemia, hepatosplenomegaly, leukocytosis with 90% of lymphocytes, granulocytopenia, anemia, trombocytopenia, hyperferritinemia and pathological findings in cerebrospinal fluid. The patient had decreased frequency of NK cells and low NK cell activity in peripheral blood. Bone marrow aspiration analysis showed degenerative changes of histocyte cells, with preserved cytophages (lymphophages and erythrophages) consistent with hematophagocytic syndrome. Given that the molecular diagnosis of the known mutations in genes PRF1 and UNC13D showed a mutation in UNC13D, the diagnosis of familial hemophagocytic lymphohistiocytosis subtype 3 was established. HLH-2004 chemotherapy protocol was performed and partial remission with residual central nervous system disease was achieved. Hematopoietic stem cell transplantation was successfully performed with an unrelated HLA-matched donor. Familiar HLH is generally a progressive and fatal disease. Early diagnosis with molecular genetic analysis and chemoimmunotherapy followed by hematopoietic stem-cell transplantation is the best approach.
authors.affiliation: Department of Hematology and Oncology, Pediatric Clinic, Zagreb Children's Hospital, Zagreb, Croatia. gordanajakovljevic@yahoo.com
authors.forename: Gordana
authors.initials: G
authors.lastname: Jakovljević
authors.forename: Ika
authors.initials: I
authors.lastname: Kardum-Skelin
authors.forename: Srdan
authors.initials: S
authors.lastname: Rogosić
authors.forename: Srdana
authors.initials: S
authors.lastname: Culić
authors.forename: Jasminka
authors.initials: J
authors.lastname: Stepan
authors.forename: Alenka
authors.initials: A
authors.lastname: Gagro
authors.forename: Ivancica
authors.initials: I
authors.lastname: Skarić
authors.forename: Lili
authors.initials: L
authors.lastname: Mikecin
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bonevski
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisić
authors.forename: Melita
authors.initials: M
authors.lastname: Nakić
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009000:Monocytes / Q000473:pathology; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D008565:Membrane Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D050765:Qa-SNARE Proteins; C541732:STX11 protein, human; C507969:UNC13D protein, human; D054353:Perforin