Hemophagocytic lymphohistiocytosis syndrome associated with Gaucher disease type 2.

Abstract

To the Editor, We present the case of a 5.5-month-old female infant hospitalized because of fever, lethargy, pallor, poor feeding, convulsion, and developmental delay. She was the first child of the family and her parents were relatives. Physical examination revealed hepatosplenomegaly, opisthotonus, and pitting edema. Laboratory studies showed pancytopenia (WBC: 3500/mm3, Hb: 6 g/dL, Plt: 40.000/mm3), coagulopathy (PT: 19.4 s, aPTT: 41 s, fibrin degradation products: 1.8 mg/mL, D-dimer: 4 mg/L), AST of 132 U/L, ALT of 107 U/L, ALP of 313 U/L, triglycerides of 280 mg/ dL, and albumin of 2.7 g/dL. Analysis of the cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis. Serum ferritin level was 1020 ng/mL and fibrinogen level was 150 mg/dL. Other test results, including renal function tests, electrolytes, serum and urine amino acid chromatography, TORCH study, and virology studies (HIV, HCV, HBV, HAV, EBV), were normal. Blood, urine, stool, CSF, and bone marrow cultures were all negative. Bone marrow examination revealed hemophagocytosis caused by macrophages (Figure 1). It also showed an increase in the number of histiocytic cells, which was not typical of Gaucher disease. However, dried blood spot testing showed a drastic reduction of 8.45 pmol/ spot (normal range: 200-2000 pmol/spot in 20 h) in the betaglucosidase enzyme activity and confirmed the diagnosis of Gaucher disease. Since 6 of the 8 criteria of hemophagocytic lymphohistiocytosis (HLH) syndrome were observed in the patient, she was subjected to treatment with the HLH 2004 Protocol [2], broad-spectrum antibiotics, and anticonvulsant drugs while supportive measures were also taken. Despite the aforementioned efforts, the patient’s clinical condition gradually worsened and she died 10 days after the beginning of the treatment. It was not possible to study the mutations associated with primary HLH or to measure the level of sIL2R and the activity of NK cells. Informed consent was obtained.