Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations
ABSTRACT The aim of this study was to elucidate the pathologic sequence changes and associated clinical phenotypes in 9 new patients showing homozygosity for perforin gene among a total of 37 (24%) Turkish FHL families studied by linkage analysis. These 9 unrelated patients (5M/4F) were coming from consanguineous families and their presentation ages of systemic symptoms were ranged from birth to 15 years. Direct sequencing of coding exons of the perforin gene led to the identification of five different homozygous alterations. The nonsense W374X mutation was identified in three patients while four different missense mutations namely G149S, V50M, A91V and novel A523D were detected in the rest six patients.
- SourceAvailable from: Ulker Kocak[Show abstract] [Hide abstract]
ABSTRACT: Familial hemophagocytic lymphohistiocytosis (FHL) is a fatal disease of early infancy caused by defective natural killer cell activity and is characterized by fever, organomegaly, pancytopenia, and coagulopathy. Disease-causing mutations have been found in perforin, Munc 13-4 and syntaxin-11 genes. We herein describe a case of late-onset FHL with syntaxin-11 mutation in a six-year-old boy in whom only partial response was obtained by immunochemotherapy (HLH-94 protocol) and who died with persistent Epstein-Barr virus (EBV) infection. The role of EBV infection in the prognosis of FHL is discussed.The Turkish journal of pediatrics 51(4):371-4. · 0.56 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This report mainly presents the clinical and laboratory findings in a group of 15 primary hemophagocytic lymphohistiocytosis patients with central nervous system involvement (group 1) and compares some of the findings with those of 13 hemophagocytic lymphohistiocytosis patients without central nervous system involvement (group 2). Statistical analysis showed that age and sodium level at diagnosis were significantly higher while alanine aminotransferase and bilirubin levels were significantly lower in group 1 than group 2 (P < .05). There were no statistically significant differences between the 2 groups in the other clinical, laboratory, and overall survival parameters. Three patients in group 1 initially had central nervous system involvement in the absence of systemic findings, which led to the initial misdiagnosis of these patients as central nervous system disorders other than hemophagocytic lymphohistiocytosis.Journal of child neurology 12/2008; 23(11):1293-9. DOI:10.1177/0883073808319073 · 1.67 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: 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.Journal of Pediatric Hematology/Oncology 01/2009; 30(12):871-6. DOI:10.1097/MPH.0b013e31818a9577 · 0.96 Impact Factor