Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy.
Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy.
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I 型糖原累积病和 G6Pase-β 缺乏症：病因学和治疗。
DOI：
10.1038/nrendo.2010.189
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发表时间：
2010-12
期刊：
影响因子：
--
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中科院分区：
文献类型：
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糖原储存病I型（GSD-I）由两种亚型组成：GSD-Ia，葡萄糖-6-磷酸酶-α (G6Pase-α)缺乏和GSD-Ib，其特征是葡萄糖-6-磷酸（G6P）转运体（G6PT）缺乏。第三种疾病，G6Pase-β缺乏症，与这组疾病有相似之处。G6Pase-α和G6Pase-β是内质网膜上的G6P水解酶，它们依赖G6PT将G6P从细胞质转运到管腔。G6PT和G6Pase-α的功能复合物维持餐间葡萄糖稳态，而G6PT和G6Pase-β共同作用维持中性粒细胞功能和稳态。GSD-Ia和GSD-Ib患者表现出葡萄糖稳态紊乱的共同代谢表型，这在G6Pase-β缺乏症患者中并不明显。G6PT缺乏和G6Pase-β缺乏的患者表现出共同的髓系表型，而GSD-Ia患者不具有这种表型。先前的研究表明，中性粒细胞表达G6PT和G6Pase-β复合物以产生内源性葡萄糖。G6PT或G6Pase-β失活都会增加中性粒细胞凋亡，这至少在一定程度上是GSD-Ib和G6Pase-β缺乏症中中性粒细胞损失（中性粒细胞减少）和功能障碍的基础。饮食和/或粒细胞集落刺激因子治疗是可用的；然而，人们对这些疾病的许多方面仍然知之甚少。本文将讨论GSD-Ia， GSD-Ib和G6Pase-β缺乏症的病因，并重点介绍诊断和新的治疗方法，包括基因治疗。
Glycogen storage disease type I (GSD-I) consists of two subtypes: GSD-Ia, a deficiency in glucose-6- phosphatase-α (G6Pase-α) and GSD-Ib, which is characterized by an absence of a glucose-6-phosphate (G6P) transporter (G6PT). A third disorder, G6Pase-β deficiency, shares similarities with this group of diseases. G6Pase-α and G6Pase-β are G6P hydrolases in the membrane of the endoplasmic reticulum, which depend on G6PT to transport G6P from the cytoplasm into the lumen. A functional complex of G6PT and G6Pase-α maintains interprandial glucose homeostasis, whereas G6PT and G6Pase-β act in conjunction to maintain neutrophil function and homeostasis. Patients with GSD-Ia and those with GSD-Ib exhibit a common metabolic phenotype of disturbed glucose homeostasis that is not evident in patients with G6Pase-β deficiency. Patients with a deficiency in G6PT and those lacking G6Pase-β display a common myeloid phenotype that is not shared by patients with GSD-Ia. Previous studies have shown that neutrophils express the complex of G6PT and G6Pase-β to produce endogenous glucose. Inactivation of either G6PT or G6Pase-β increases neutrophil apoptosis, which underlies, at least in part, neutrophil loss (neutropenia) and dysfunction in GSD-Ib and G6Pase-β deficiency. Dietary and/or granulocyte colony-stimulating factor therapies are available; however, many aspects of the diseases are still poorly understood. This Review will address the etiology of GSD-Ia, GSD-Ib and G6Pase-β deficiency and highlight advances in diagnosis and new treatment approaches, including gene therapy.
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