糖原贮积病IV型(GSDIV),也叫安徒生病,或者支链淀粉病,是一种由糖原分支酶(GBE,1,4-α-葡聚糖分支酶)缺乏症,继发于GBE1基因的致病变体。发病率评估为活产的1:600000至1:800000。GBE缺乏导致结构异常的过度沉积,受影响组织中的支链淀粉样糖原(肝脏,骨骼肌,心,神经系统,等。).诊断通常以组织学发现为指导,并通过GBE活性缺乏和分子研究证实。严重的GSDIV神经肌肉形式非常罕见,预后不良。这些形式的鉴定和表征对于进一步怀孕的遗传咨询很重要。在这里我们描述临床,组织学,酶,和来自8个家庭的10个病例的分子发现,迄今为止报道的最大病例系列,严重的神经肌肉形式的GSDIV以及文献综述。产前主要特征是:胎儿运动障碍变形序列或关节挛缩/关节挛缩常伴有肌肉萎缩,胎动减少,囊性水瘤,和/或胎儿水肿。如果怀孕持续到足月,出生时观察到的主要临床特征是严重的低张力和/或肌肉萎缩,需要机械通风,心肌病,逆行,和关节病。我们所有的患者在1个月内死产或死亡。此外,我们确定了五个新的GBE1变体。
Glycogen storage disease type IV (GSD IV), also called Andersen disease, or amylopectinosis, is a highly heterogeneous autosomal recessive disorder caused by a glycogen branching enzyme (GBE, 1,4-alpha-glucan branching enzyme) deficiency secondary to pathogenic variants on GBE1 gene. The incidence is evaluated to 1:600 000 to 1:800 000 of live births. GBE deficiency leads to an excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues (liver, skeletal muscle, heart, nervous system, etc.). Diagnosis is often guided by histological findings and confirmed by GBE activity deficiency and molecular studies. Severe neuromuscular forms of GSD IV are very rare and of disastrous prognosis. Identification and characterization of these forms are important for genetic counseling for further pregnancies. Here we describe clinical, histological, enzymatic, and molecular findings of 10 cases from 8 families, the largest
case series reported so far, of severe neuromuscular forms of GSD IV along with a literature review. Main antenatal features are: fetal akinesia deformation sequence or
arthrogryposis/joint contractures often associated with muscle atrophy, decreased fetal movement, cystic hygroma, and/or hydrops fetalis. If pregnancy is carried to term, the main clinical features observed at birth are severe hypotonia and/or muscle atrophy, with the need for mechanical ventilation, cardiomyopathy, retrognathism, and
arthrogryposis. All our patients were stillborn or died within 1 month of life. In addition, we identified five novel GBE1 variants.