14 research outputs found

    Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation

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    We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN

    CKD-MBD after kidney transplantation

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    Successful kidney transplantation corrects many of the metabolic abnormalities associated with chronic kidney disease (CKD); however, skeletal and cardiovascular morbidity remain prevalent in pediatric kidney transplant recipients and current recommendations from the Kidney Disease Improving Global Outcomes (KDIGO) working group suggest that bone disease—including turnover, mineralization, volume, linear growth, and strength—as well as cardiovascular disease be evaluated in all patients with CKD. Although few studies have examined bone histology after renal transplantation, current data suggest that bone turnover and mineralization are altered in the majority of patients and that biochemical parameters are poor predictors of bone histology in this population. Dual energy X-ray absorptiometry (DXA) scanning, although widely performed, has significant limitations in the pediatric transplant population and values have not been shown to correlate with fracture risk; thus, DXA is not recommended as a tool for the assessment of bone density. Newer imaging techniques, including computed tomography (quantitative CT (QCT), peripheral QCT (pQCT), high resolution pQCT (HR-pQCT) and magnetic resonance imaging (MRI)), which provide volumetric assessments of bone density and are able to discriminate bone microarchitecture, show promise in the assessment of bone strength; however, future studies are needed to define the value of these techniques in the diagnosis and treatment of renal osteodystrophy in pediatric renal transplant recipients

    Cooperating, congenital neutropenia–associated Csf3r and Runx1 mutations activate pro-inflammatory signaling and inhibit myeloid differentiation of mouse HSPCs

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    Patients with the pre-leukemia bone marrow failure syndrome called severe congenital neutropenia (CN) have an approximately 15% risk of developing acute myeloid leukemia (AML; called here CN/AML). Most CN/AML patients co-acquire CSF3R and RUNX1 mutations, which play cooperative roles in the development of AML. To establish an in vitro model of leukemogenesis, we utilized bone marrow li

    Relato de um caso de neutropenia congĂȘnita grave em um lactente jovem A case report of severe congenital neutropenia in a young infant

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    OBJETIVO: Relatar um caso de neutropenia congĂȘnita grave e alertar os pediatras sobre tal diagnĂłstico em pacientes jovens, com infecçÔes recorrentes. DESCRIÇÃO DO CASO: Lactente jovem com 45 dias de vida, com histĂłria de febre alta, letargia, recusa alimentar e hemogramas repetidos com leucopenia importante Ă  custa de polimorfonucleares. A hipĂłtese diagnĂłstica foi confirmada pelo aspirado de medula Ăłssea, que mostrou hipoplasia de sĂ©rie granulocĂ­tica e completa ausĂȘncia de neutrĂłfilos maduros. Foi introduzida antibioticoterapia de largo espectro e estimulador da formação de colĂŽnias de granulĂłcitos. O paciente evoluiu para Ăłbito em decorrĂȘncia de complicaçÔes infecciosas apĂłs 21 dias de internação. COMENTÁRIOS: Trata-se de um lactente jovem, portador de uma rara desordem congĂȘnita que leva Ă  intensa neutropenia, deixando-o vulnerĂĄvel a infecçÔes graves e potencialmente fatais. À internação, o paciente apresentava sinais e sintomas sugestivos de sepse, sendo introduzido antibioticoterapia de amplo espectro, necessĂĄria por se tratar de lactente jovem, neutropĂȘnico e febril. A hipĂłtese diagnĂłstica se baseou na histĂłria clĂ­nica e nos leucogramas alterados, sendo posteriormente confirmada pelo aspirado de medula Ăłssea. Foi introduzido o estimulador da formação de colĂŽnias de granulĂłcitos, que geralmente Ă© efetivo, porĂ©m, nesse caso, nĂŁo houve sucesso e o paciente evoluiu para Ăłbito devido Ă  grave infecção.<br>OBJECTIVE: To report a case of severe congenital neutropenia and alert pediatricians about its diagnosis in young patients with recurrent infectious diseases. CASE DESCRIPTION: Young infant with 45 days of life, with a history of high fever, lethargy, poor feeding and repeated blood counts showing significant leucopenia due to a significant decrease of polymorphonuclear cells. The diagnosis was confirmed by bone marrow aspirate showing hypoplasia of the granulocytic series and complete absence of mature neutrophils. Treatment was started with broad-spectrum antibiotic therapy and granulocyte colony-stimulating factor, but the patient died due to infectious complications 21 days after hospital admission. COMMENTS: This is a young infant with a rare congenital disorder that leads to severe neutropenia and, therefore, susceptible to potentially fatal infections. In the hospital the infant showed signs and symptoms of sepsis. The diagnosis was based on the clinical history and the presence of repeated altered white cell counts and it was confirmed by bone marrow aspirate. Granulocyte colony-stimulating factor is generally effective, but, in this case, the patient died with a severe infection
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