Mutations of the ELANE gene cause severe congenital neutropenia with periodontal disease: a case report / 华西口腔医学杂志

Severe congenital neutropenia is a rare disorder characterized by a consistently low absolute neutrophil count and periodontal disease. This report describes the case of an ELANE mutationin a patient with gingival bleeding and tooth mobility. Oral examination showed active periodontal infection of the primary dentition accompanied by alveolar bone loss in the posterior region. The patient was diagnosed with severe congenital neutropenia 1 year after multidisciplinary consultation. Treatment of the systemic disease and effective oral health education over a 3-year follow-up period relieved the periodontal infection and created favorable conditions for future repair.

Neutropenia congênita / Congenital neutropenia

Buscamos aqui revisar os mecanismos imunopatológicos relacionados à neutropenia congênita.O termo neutropenia congênita é utilizado para designar uma série de distúrbios neutropênicos,de caráter permanente, intermitente, grave (< 500 neutrófilos/mm3 de sangue), ou moderado(entre 500-1.500 neutrófilos/mm3 de sangue), que podem acometer pele e mucosa do tratorespiratório e gastrintestinal. Quando a neutropenia é diagnosticada, ela deve ser distinguidadas formas adquiridas, incluindo a neutropenia pós-viral e a autoimune, da forma congênita,que pode ser uma enfermidade isolada ou fazer parte de uma doença genética. Cinquenta porcento das formas congênitas de neutropenia apresentam manifestação extra-hematopoiéticacom resposta imune adaptativa normal e infecções recorrentes no início da vida. O tratamentodestes pacientes tem por objetivo o controle e a prevenção de infecções através do uso profiláticode antibióticos, e outra forma de tratamento consiste na utilização de fator estimuladorde colônia de granulócitos recombinante humano (rHUG-CSF), que aumenta o número degranulócitos, diminui o número infecções e melhora de forma significativa a sobrevida e qualidadede vida. A revisão foi realizada por levantamento bibliográfico de banco de dados obtidosatravés de pesquisa direta, LILACS, MEDLINE e capítulos de livros. A revisão literária demonstraa importância dos neutrófilos pela defesa do hospedeiro contra micro-organismos, e defeitosgenéticos que envolvem estas células acarretam maior susceptibilidade a infecções microbianasem locais como pele e mucosa do trato respiratório e gastrintestinal. Estes defeitos genéticosdos neutrófilos envolvem o seu número, função, ou ambos. Como estes defeitos envolvendofagócitos são de caráter congênito e hereditário, as crianças são os pacientes predominantes. Osneutrófilos apresentam um papel importante na imunidade inata, prevenindo o surgimento deinfecções de repetição. O tratamento com rHUG-CSF aumenta o número de granulócitos, diminuio número de novas infecções e melhora de forma significativa a sobrevida e qualidade de vida.O transplante de células-tronco hematopoiéticas é indicado em casos refratários ao tratamentocom rHUG-CSF que apresentam infecções recorrentes graves e resistência ao tratamento semdetecção de mielodisplasia/leucemia.

Here we aim to review pathogenic mechanisms related to congenital neutropenia. The termcongenital neutropenia has been used to designate a series of neutropenic disorders that canbe permanent, intermittent, severe (< 500 neutrophils/mm3) or moderate (500-1500 neutrophils/mm3), which could affect the skin and mucosa of the respiratory and gastrointestinal tracts. Whenneutropenia is diagnosed, it is necessary to distinguish between the acquired form, includingpost-viral and autoimmune neutropenia, and the congenital form, a disease that can occur eitheralone or as part of a genetic disease. Fifty percent of the congenital forms of neutropenia haveextra-hematopoietic manifestations, with normal adaptive immune response and recurrent infections in early life. Treatment of these patients focuses primarily on controlling and preventing infections through the use of prophylactic antibiotics; another treatment approach is the use of recombinant human granulocyte colony-stimulating factor (rHUG-CSF), which increases the number of granulocytes, reduces the number of infections, and significantly improves survival rates and quality of life in these patients. Papers were directly searched on the LILACS and MEDLINE database Book chapters were also reviewed. The literature reviewed underscores theimportance of neutrophils for host defense against microorganisms and the association betweengenetic defects involving these cells and an increased susceptibility to microbial infections inthe skin and mucosa of the respiratory and gastrointestinal tracts. Genetic defects may affectneutrophil number, function, or both. Because defects involving phagocytes have a congenitaland hereditary origin, children are the most common patients. Neutrophils have an importantrole in innate immunity, preventing the emergence of recurrent infections. Treatment withrHUG-CSF increases the number of granulocytes, decreases the number of new infections, andsignificantly improves survival rates and quality of life. Hematopoietic stem cell transplantationis indicated in patients refractory to rHUG-CSF treatment with severe and recurrent infectionsand resistance to treatment with no detection of myelodysplasia/leukemia.

New progress in genetic mechanisms of congenital neutropenia / 中华实用儿科临床杂志

Congenital neutropenia (CN) is a heterogeneous group of disorders in the inherited bone marrow failure syndromes (IBMFS),characterized by a severe decrease in the number of blood neutrophils,and a maturation arrest of bone marrow progenitor cells mainly at the promyelocyte/myeloid stage,and most of congenital neutropenia patients are susceptibility to bacterial infections in clinically.In recent years,the mutations in ELANE,GFI1,HAX1,G6PC3,WAS,CSF3R and so on are associated with the occurrence and development of CN,and with the further research,more new virulence gene will be found gradually.