Jakovljević Gordana, Kardum-Skelin Ika, Rogosić Srdan, Culić Srdana, Stepan Jasminka, Gagro Alenka, Skarić Ivancica, Mikecin Lili, Bonevski Aleksandra, Barisić Ingeborg, Nakić Melita
Department of Hematology and Oncology, Pediatric Clinic, Zagreb Children's Hospital, Zagreb, Croatia.
Coll Antropol. 2010 Jun;34(2):631-4.
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.
家族性噬血细胞性淋巴组织细胞增生症（FLH）是一种常染色体隐性遗传的多系统疾病。这种细胞毒性缺陷是一种危及生命的病症，其特征为发热、皮疹、脾肿大、血细胞减少和神经学表现。PRF1、UNC13D和STX11基因缺陷是约40%-50%原发性病例的病因。化疗免疫疗法联合造血干细胞移植改善了疾病预后。我们报告一例6周龄男婴，其表现为发热、弥漫性皮疹、弥散性血管内凝血、纤维蛋白原血症、高甘油三酯血症、肝脾肿大、白细胞增多伴90%淋巴细胞、粒细胞减少、贫血、血小板减少、高铁蛋白血症以及脑脊液病理检查异常。该患者外周血自然杀伤（NK）细胞频率降低且NK细胞活性低下。骨髓穿刺分析显示组织细胞有退行性改变，吞噬细胞（淋巴细胞性和红细胞性吞噬细胞）保存完好，符合噬血细胞综合征。鉴于已知PRF1和UNC13D基因突变的分子诊断显示UNC13D存在突变，故确诊为3型家族性噬血细胞性淋巴组织细胞增生症。采用HLH-2004化疗方案，实现了部分缓解，但仍残留中枢神经系统疾病。采用一名HLA匹配的无关供者成功进行了造血干细胞移植。家族性噬血细胞性淋巴组织细胞增生症通常是一种进行性致命疾病。通过分子遗传学分析进行早期诊断，继以化疗免疫疗法和造血干细胞移植是最佳治疗方法。
