Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations

Okur, Hamza; Balta, Günay; Akarsu, Nurten; Öner, Ahmet Faik; Patıroğlu, Türkan; Bay, Ali; Şaylı, Tülin Revide; Ünal, Şule; Gürgey, Aytemiz

doi:10.1016/j.leukres.2007.11.033

Cited by 27 publications

(26 citation statements)

References 23 publications

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“…Both primary and secondary HLH are more common in our country than elsewhere [11][12][13][14]. As the disease shows autosomal recessive inheritance, it is probable that the present case, with parental consanguinity, might have had a primary HLH.…”

Section: Discussionmentioning

confidence: 85%

Niemann - Pick disease associated with hemophagocytic syndrome

Karaman¹,

Urgancı²,

Kutluk³

et al. 2010

Turk J Hematol

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Hemophagocytic lymphohistiocytosis (HLH) is a disease characterized by phagocytosis of blood cells by macrophages within the lymphoreticular tissue. It can develop secondary to some diseases or be familial as a result of genetic mutations. Niemann-Pick disease (NPD) is a very rare lipid storage disease. A three-month-old girl presented with high fever (39°C), abdominal distension and paleness. The parents were consanguineous. The liver and spleen were palpable 10 cm and 11 cm below the costal margins, respectively. Bicytopenia (Hb: 5.5 g/dl, platelet: 77000/mm 3 ), hypertriglyceridemia (351 mg/ dl), hyperferritinemia (>1500 ng/dl) and hypofibrinogenemia (120 mg/dl) were detected. Bone marrow aspiration demonstrated foam cells and hemophagocytosis by macrophages and Niemann-Pick cells. Lysosomal sphingomyelinase activity was 0.24 nmol/h/mg/protein (normal: 0.86-2.8). Due to the parents' refusal of further evaluation, the nature of HLH as primary or secondary could not be determined. To the best of our knowledge, this is the first case of NPD associated with HLH and the first demonstration of hemophagocytosis by Niemann-Pick cells. (Turk J Hematol 2010; 27: 303-7) Key words: Niemann-Pick disease, hemophagocytic syndrome, hemophagocytosis by NiemannPick cell, hemophagocytosis, hemophagocytic lymphohistiocytosis, HLH

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Section: Discussionmentioning

confidence: 85%

Niemann - Pick disease associated with hemophagocytic syndrome

Karaman¹,

Urgancı²,

Kutluk³

et al. 2010

Turk J Hematol

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“…Due to the very high rate of consanguineous marriages (21%) in Turkey, the expected incidence of HLH should be high as well. Many reports on FHLH in Turkish patients justify this conclusion [11][12][13]. Although there are no nationwide epidemiologic data, in one study, the frequency of the HLH among hospitalized patients was found to be 7.5/10000, and the rate of consanguineous marriage was reported as 68% in HLH patients [14].…”

Section: Discussionmentioning

confidence: 96%

Clinical and laboratory data of primary hemophagocytic lymphohistiocytosis: A retrospective review of the Turkish Histiocyte Study Group

Fışgın¹,

Patıroğlu²,

Ozdemir³

et al. 2010

Turk J Hematol

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Objective: This study analyzes the clinical and laboratory findings of children with primary hemophagocytic lymphohistiocytosis (HLH) followed in various referral centers of Turkey. Materials and Methods: A simple three-page questionnaire prepared by the Turkish Histiocyte Study Group was used for documentation of patient data. Results: Age at diagnosis varied from 0.6 to 78 months (median±SD, 16.5±26.1). Sex distribution was almost equal (F/M=10/12). The frequencies of parental consanguinity and sibling death in the family history were 100% and 81.1%, respectively. The most common clinical findings were hepatomegaly (100%) and fever (95%). The most common laboratory findings were anemia (100%), hyperferritinemia (100%) and thrombocytopenia (90.9%). Triglyceride and total bilirubin levels in the deceased versus surviving group appear to be high (triglyceride: 394±183 mg/dl, 289±7 mg/dl; total bilirubin: 2.7±6.9 mg/dl, 0.5±1.2 mg/ dl, respectively).

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“…Molecular genetic analysis was performed as previously described in all patients except one. 16,17 In case 4, only sequential analyses for perforin gene was performed.…”

Section: Methodsmentioning

confidence: 99%

“…[9][10][11][12][13][14] While the literature data on HLH have expanded recently, the neonatal HLH cases have usually been reported together with other age groups of patients. 3,[15][16][17][18] We thus decided to present separately the clinical and laboratory characteristics of 8 patients with primary HLH who presented in our center during the neonatal period.…”

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confidence: 99%

Neonatal Primary Hemophagocytic Lymphohistiocytosis in Turkish Children

Gürgey¹,

Ünal²,

Okur³

et al. 2008

Journal of Pediatric Hematology/Oncology

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Although the data on hemophagocytic lymphohistiocytosis (HLH) has gradually increased, the neonatal-onset HLH patients have usually been reported as case reports or together with other age groups of patients. The aim of this study was to draw attention to the clinical and laboratory characteristics of neonatal HLH cases. Herein, the data of 8 primary, neonatal-onset HLH patients are reported. Mutational analyses were performed in 7 of the patients and mutations in UNC13D gene were detected in 3 of the patients, whereas 2 patients were found to have perforin gene mutation. Four of the patients were symptomatic within the initial 10 days of life. One patient with perforin mutation (1122 G>A) had a very severe clinical course and died on the seventh day of life before receiving any specific treatment. Another patient with UNC13D 2783 G>C, who became symptomatic on the sixth day of life, underwent early hematopoietic stem cell transplantation and is currently alive at 8 years of age. Two of these 4 patients had extensively high serum ferritin levels mimicking neonatal hemochromatosis. Of the 4 patients who became symptomatic after 20th day of newborn period, 1 was found to have perforin gene mutation (445 G>A) and 2 siblings were detected to have a missense mutation in UNC13D (640 C>T) gene. The latter patients with UNC13D mutations could survive 3 and 4 months, although their parents ceased therapy. The patient with perforin mutation survived 11 months.

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Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations

Cited by 27 publications

References 23 publications

Niemann - Pick disease associated with hemophagocytic syndrome

Niemann - Pick disease associated with hemophagocytic syndrome

Clinical and laboratory data of primary hemophagocytic lymphohistiocytosis: A retrospective review of the Turkish Histiocyte Study Group

Neonatal Primary Hemophagocytic Lymphohistiocytosis in Turkish Children

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