Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Pediatrics. 2011 Nov;128(5):e1233-41. doi: 10.1542/peds.2011-0078. Epub 2011 Oct 24.
G(M2) gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile G(M2) gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature.
Patients with infantile G(M2) gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature.
Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival.
We studied the timing of regression in 97 cases of infantile G(M2) gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions.
G（M2）神经节苷脂贮积症是由于溶酶体β-己糖胺酶的遗传性缺乏引起的，导致脑内神经节苷脂堆积。婴儿期发病导致快速神经退行性变，在 4 岁前死亡。我们旨在根据患者调查和对现有文献的全面回顾，量化婴儿型 G（M2）神经节苷脂贮积症的功能下降速度。
通过国家泰萨克斯氏症及相关疾病协会（NTSAD）的问卷调查，对 237 例婴儿型 G（M2）神经节苷脂贮积症患者进行调查。这些数据由 NTSAD 数据库中的生存数据和文献调查补充。详细的回顾性调查来自 97 名患者。5 名接受过造血干细胞移植的患者单独进行评估。其余 92 名患者的死亡率与 NTSAD 数据库中的 103 名患者和文献中报道的 121 名患者的死亡率相当。
发病时常见的症状是发育停滞（83%）、惊跳（65%）和低张力（60%）。所有 55 名无需支撑就能独坐的患者在 1 年内都丧失了这种能力。个体功能测量彼此相关，但与生存无关。胃管放置与延长生存时间相关。泰萨克斯和桑德霍夫变异型之间没有差异。造血干细胞移植与延长生存时间无关。
我们研究了 97 例婴儿型 G（M2）神经节苷脂贮积症的退行时间，得出结论，临床疾病进展与生存无关，这可能是由于随着时间的推移，支持性治疗的改善产生了影响。然而，功能测量是可量化的，可以为未来干预措施的效力计算和研究设计提供信息。
