Familial hemophagocytic lymphohistiocytosis in a 6-week-old male infant.
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.
Jakovljević
Gordana
G
Department of Hematology and Oncology, Pediatric Clinic, Zagreb Children's Hospital, Zagreb, Croatia. gordanajakovljevic@yahoo.com
Kardum-Skelin
Ika
I
Rogosić
Srdan
S
Culić
Srdana
S
Stepan
Jasminka
J
Gagro
Alenka
A
Skarić
Ivancica
I
Mikecin
Lili
L
Bonevski
Aleksandra
A
Barisić
Ingeborg
I
Nakić
Melita
M
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
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