Severe and recurrent infections identify severe congenital neutropenia and primary immunodeficiencies in pediatric isolated neutropenia
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Congenital Neutropenia
Acute lymphoblastic leukemia (ALL) presenting with neutropenia alone is very rare. We describe a newborn with an early life-threatening infection, severe neutropenia and bone marrow findings compatible with severe congenital neutropenia (SCN). She was treated with granulocyte colony-stimulating factor (G-CSF) with complete neutrophil recovery. Three months later she developed a pro-B ALL. We identified a rare loss of 5'-MLL present at the diagnosis of SCN and ALL by FISH analysis using two different MLL (11q23) probes. Molecular analyses for SCN causing mutations (ELA-2, HAX-1 and G6PC3) and for somatic mutations of the CSF3R gene were negative. The early presence of 5'-MLL loss in bone marrow samples may favor the diagnosis of de novo ALL. Nevertheless, the genetic background for SCN is heterogeneous and a non-described mutation for SCN followed by a secondary ALL cannot be excluded. Further genetic investigation may be useful to gain insight into this rare condition in children.
Congenital Neutropenia
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Introduction: Severe congenital neutropenia (SCN) includes a group of genetic disorders which cause to arrest of neutrophil maturation. SCN can be associated with heterogenous group of genetic defects in ELANE, GFI1, HAX1, G6PC3, JAGN1, VPS45 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene. Aim: Here we report a patient who has a HAX1 mutation presented with cyclic manner. Case Report: A 6 year old female patients was admitted with recurrent apthous stomatitis. We followed the patient as cyclic neutropenia according to complete blood count results 2 times for 6 weeks. After persistant neutropenia developed during a severe varicella infection, we analysed HAX1 mutation, the result was interesting and incompatible with reported cyclic neutropenia patients. Conclusion: We suggest that HAX1 deficiency should be thought in patients who have normal neutrophil counts in the between of infections.
Congenital Neutropenia
Cyclic neutropenia
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Neutropenia is common in the practice of both primary care physicians and physicians of sub-speciality. Congenital neutropenia are rare diseases; they can be both isolated independent diseases and accompany a number of other inborn errors of immunity. The clinical course of neutropenia can range from asymptomatic in patients with mild neutropenia to life-threatening infections in cases of severe neutropenia. Treatment of congenital neutropenia remains discutable to this day. The most common and accessible method of treatment of severe congenital neutropenia is granulocyte colony-stimulating factor, although it does not cure the disease and does not prevent the development of malignant transformation. On the other hand, the use of granulocyte colony-stimulating factor in the correct doses can improve the clinical course of the disease, the quality of life of patients, avoid severe septic complications. Hematopoietic stem cell transplant is an effective treatment for severe congenital neutropenia that does not respond to granulocyte colony-stimulating factor therapy. Modern methods of genetic therapy open new perspectives in the treatment of patients with severe congenital neutropenia. No conflict of interests was declared by the author. Key words: congenital neutropenia, treatment, Granulocyte colony-stimulating factor (G-CSF).
Congenital Neutropenia
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Abstract Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations. Pediatr Blood Cancer 2011; 57: 332–335. © 2011 Wiley‐Liss, Inc.
Congenital Neutropenia
Cyclic neutropenia
Promyelocyte
Blood cancer
Compound heterozygosity
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Neonatology
Congenital Neutropenia
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Abstract Congenital neutropenia comprises a variety of genetically heterogeneous phenotypic traits. Molecular elucidation of the underlying genetic defects has yielded important insights into the physiology of neutrophil differentiation and function. Non-syndromic variants of congenital neutropenia are caused by mutations in ELA2, HAX1, GFI1, or WAS. Syndromic variants of congenital neutropenia may be due to mutations in genes controlling glucose metabolism (SLC37A4, G6PC3) or lysosomal function (LYST, RAB27A, ROBLD3/p14, AP3B1, VPS13B). Furthermore, defects in genes encoding ribosomal proteins (SBDS, RMRP) and mitochondrial proteins (AK2, TAZ) are associated with congenital neutropenia syndromes. Despite remarkable progress in the field, many patients with congenital neutropenia cannot yet definitively be classified by genetic terms. This review addresses diagnostic and therapeutic aspects of congenital neutropenia and covers recent molecular and pathophysiological insights of selected congenital neutropenia syndromes.
Congenital Neutropenia
Cyclic neutropenia
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Congenital Neutropenia
Pathophysiology
Cyclic neutropenia
Genetic syndromes
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Purpose of review A decade after the availability of hematopoietic growth factors, the long-term outcome of severe congenital neutropenia has dramatically changed. The prolonged survival of neutropenic patients receiving hematopoietic growth factors has drawn attention to the heterogeneity of this disease and to the complications of treatment. The dose of granulocyte colony stimulating factor that is required to obtain normal levels of circulating neutrophils and to prevent fever and infections is quite variable among patients, but is higher in children with severe congenital neutropenia than in those with other conditions of neutropenia. Moreover, leukemic transformation during treatment is not observed in all patients, but is more typical of severe congenital neutropenia and Shwachman-Diamond patients. Recent findings In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia. Summary Although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia.
Congenital Neutropenia
Cyclic neutropenia
Hypogammaglobulinemia
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Congenital Neutropenia
Cyclic neutropenia
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The term congenital neutropenia embrace a family neutropenic disorders, that can be permanent or intermittent, severe or pleasant, which can cause repercussions in other organ systems. Neutropenia can range from mild pyogenic infections to life-threatening sepsis, and each successive infection can leave permanent sequelae. The risk of infection is approximately inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2G/l. About half of the forms of congenital neutropenia, without extrahematopoietic manifestations and normal adaptive immunity, are due to mutations in neutrophil elastase. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. The difficulty in suspected diagnosis congenital neutropenia and, consequently, the time to start treatment can lead to infectious complications and put the patients’ life at risk.
Congenital Neutropenia
Absolute neutrophil count
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