Glycogen storage disease IV (GSD IV), caused by a defect in GBE1, is a clinically heterogeneous disorder. A classical hepatic form and a neuromuscular form have been described. The severe neuromuscular form presents as a fetal akinesia deformation sequence or a congenital subtype. We ascertained three unrelated families with fetuses/neonates who presented with fetal akinesia deformation sequence to our clinic for genetic counseling. We performed a detailed clinical evaluation, exome sequencing, and histopathology examination of two fetuses and two neonates from three unrelated families presenting with these perinatally lethal neuromuscular forms of GSD IV. Exome sequencing in the affected fetuses/neonates identified four novel pathogenic variants (c.1459G>T, c.144-1G>A, c.1680C>G, and c.1843G>C) in GBE1 (NM_000158). Histopathology examination of tissues from the affected fetuses/neonate was consistent with the diagnosis. Here, we add three more families with the severe perinatally lethal neuromuscular forms of GSD IV to the GBE1 mutation spectrum.

中文翻译：

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GBE1中的新型致病变体导致胎儿运动障碍变形序列和糖原贮积病IV型的严重神经肌肉形式。

由GBE1缺陷引起的糖原贮积病IV（GSD IV）是一种临床异质性疾病。已经描述了经典的肝形式和神经肌肉形式。严重的神经肌肉形式表现为胎儿运动障碍变形序列或先天性亚型。我们确定了三个不相关的胎儿/新生儿家族，他们向我们的诊所提出了胎儿运动障碍变形序列，以进行遗传咨询。我们进行了详细的临床评估，外显子组测序和来自三个无关家庭的两个胎儿和两个新生儿的病理学检查，这些三个家族涉及这些围生期致死性神经肌肉形式的GSD IV。在受影响的胎儿/新生儿中的外显子组测序确定了GBE1（NM_000158）中的四个新的致病变异（c.1459G> T，c.144-1G> A，c.1680C> G和c.1843G> C）。受影响的胎儿/新生儿的组织的组织病理学检查与诊断一致。在这里，我们将另外三个具有严重围产期致死性神经肌肉形式GSD IV的家庭添加到GBE1突变谱中。