Congenital neutropenia: diagnosis, molecular bases and patient management.
Congenital neutropenia: diagnosis, molecular bases and patient management.
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DOI：
10.1186/1750-1172-6-26
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发表时间：
2011-05-19
影响因子：
3.7
通讯作者：
Chantelot CB
中科院分区：
文献类型：
--
作者：
Donadieu J;Fenneteau O;Beaupain B;Mahlaoui N;Chantelot CB
术语先天性中性粒细胞减少症包括一个家族的永久性和间歇性、重度（<0.5 G/l）或轻度（0.5-1.5 G/l）的中性粒细胞减少症疾病，其也可能影响其他器官系统，如胰腺、中枢神经系统、心脏、肌肉和皮肤。中性粒细胞增多症可导致危及生命的化脓性感染、急性龈口炎和慢性牙周炎，每次连续感染都可能留下永久性后遗症。感染的风险与循环多形核白细胞计数大致成反比，计数低于0.2 G/l时尤其高。当检测到中性粒细胞减少症时，应尝试确定病因，区分获得性形式（最常见的，包括病毒感染后中性粒细胞减少症和自身免疫性中性粒细胞减少症）和先天性形式（可能是孤立的或复杂遗传疾病的一部分）。除了种族中性粒细胞减少症是一种常见但轻微的先天性形式，可能具有多基因遗传，所有其他形式的先天性中性粒细胞减少症都非常罕见，具有单基因遗传，可能是X连锁或常染色体，隐性或显性。大约一半的先天性中性粒细胞减少症的形式，没有额外的造血表现和正常的适应性免疫是由于中性粒细胞弹性蛋白酶（ELANE）突变。一些患者在生命早期具有严重的永久性中性粒细胞减少症和频繁的感染，而另一些患者具有轻度间歇性中性粒细胞减少症。先天性中性粒细胞减少症也可能与广泛的器官功能障碍相关，例如在Shwachman-Diamond综合征（与胰腺功能不全相关）和糖原累积病Ib型（与糖原累积综合征相关）中。到目前为止，已经确定了12种血小板减少症的分子基础。严重慢性中性粒细胞减少症的治疗应侧重于预防感染。它包括抗菌预防，通常使用甲氧苄啶-磺胺甲恶唑，也包括粒细胞集落刺激因子（G-CSF）。G-CSF大大改善了这些患者的前景。它通常耐受性良好，但潜在的不良反应包括血小板减少症、肾小球肾炎、血管炎和骨质疏松症。在先天性中性粒细胞减少症患者中，长期使用G-CSF治疗，特别是高剂量治疗，可增加自发性白血病的风险。
The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.
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影响因子：
3.2
作者：
Beaupain, Blandine;Leblanc, Thierry;Donadieu, Jean
通讯作者：
Donadieu, Jean
DOI：
10.3324/haematol.2009.009001
发表时间：
2009-10-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
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影响因子：
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作者：
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通讯作者：
Fischer, Alain
DOI：
10.3324/haematol.2009.018481
发表时间：
2010-09-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
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作者：
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Lamy, Thierry