The Clinical and Molecular Spectrum of GM1 Gangliosidosis
The Clinical and Molecular Spectrum of GM1 Gangliosidosis
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DOI：
10.1016/j.jpeds.2019.08.016
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发表时间：
2019-12-01
影响因子：
5.1
通讯作者：
Hennermann, Julia B.
中科院分区：
文献类型：
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作者：
Arash-Kaps, Laila;Komlosi, Katalin;Hennermann, Julia B.
目的评价GM 1神经节苷脂沉积症患者的临床表现，并确定是否有特异性的临床或生化体征可以导致及时诊断。研究设计我们回顾性分析了来自德国和奥地利5个代谢中心的22例GM 1神经节苷脂沉积症患者的临床、生化和遗传学资料。三是少年型。婴儿期的诊断延迟为6 +/- 2.6个月，晚期婴儿期为2.6 +/- 3.79年，青少年型为14 +/- 3.48年。粗糙的面部特征，樱桃红色斑点，内脏肿大只发生在婴儿型患者。晚期婴儿型和青少年型患者表现出不同的神经系统症状。17名患者出现肌张力障碍，14名患者出现吞咽困难。实验室分析显示ASAT浓度（13/20）、壳三糖苷酶活性（12/15）和病理性尿寡糖（10/19）增加。基因型分析显示19例患者中有23个致病或可能致病的突变，其中7个是新的变异。在大多数情况下，一个明确的基因型-表型相关性被发现。结论GM 1神经节苷脂沉积症的诊断往往是延迟的，特别是在病情较轻的患者。即使没有内脏症状或樱桃红点，进行性神经变性和痉挛性肌张力障碍性运动障碍患者也应考虑GM 1神经节苷脂沉积症。ASAT血清浓度和壳三糖苷酶活性可能对筛查GM 1神经节苷脂沉积症有价值。
Objective To evaluate the clinical presentation of patients with GM1 gangliosidosis and to determine whether specific clinical or biochemical signs could lead to a prompt diagnosis.Study design We retrospectively analyzed clinical, biochemical, and genetic data of 22 patients with GM1 gangliosidosis from 5 metabolic centers in Germany and Austria.Results Eight patients were classified as infantile, 11 as late-infantile, and 3 as juvenile form. Delay of diagnosis was 6 +/- 2.6 months in the infantile, 2.6 +/- 3.79 years in the late-infantile, and 14 +/- 3.48 years in the juvenile form. Coarse facial features, cherry red spots, and visceromegaly occurred only in patients with the infantile form. Patients with the late-infantile and juvenile forms presented with variable neurologic symptoms. Seventeen patients presented with dystonia and 14 with dysphagia. Laboratory analysis revealed an increased ASAT concentration (13/20), chitotriosidase activity (12/15), and pathologic urinary oligosaccharides (10/19). Genotype analyses revealed 23 causative or likely causative mutations in 19 patients, 7 of them being novel variants. In the majority, a clear genotype-phenotype correlation was found.Conclusions Diagnosis of GM1 gangliosidosis often is delayed, especially in patients with milder forms of the disease. GM1 gangliosidosis should be considered in patients with progressive neurodegeneration and spastic-dystonic movement disorders, even in the absence of visceral symptoms or cherry red spots. ASAT serum concentrations and chitotriosidase activity may be of value in screening for GM1 gangliosidosis.