The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment.
The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment.
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DOI：
10.1016/j.neulet.2021.136195
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发表时间：
2021-11-01
影响因子：
2.5
通讯作者：
Tifft CJ
中科院分区：
文献类型：
--
作者：
Toro C;Zainab M;Tifft CJ
GM 2神经节苷脂沉积症、泰-萨二氏病（TSD）、桑德霍夫病（SD）和GM 2激活剂缺乏症是罕见的、进行性的、神经退行性溶酶体贮积症（LSD），均具有致死性且无有效治疗。严重的婴儿型TSD，最初称为家族性黑蒙性白痴，于1899年由英国眼科医生Waren Tay和纽约神经学家Bernard Sachs在德系犹太血统的婴儿中首次独立描述[1]。由于受累患者神经元中的特征性樱桃红斑和多层胞质体，TSD是由溶酶体水解酶或转运蛋白缺陷引起的70多种LSD的原型[2]。从1950年开始，布鲁克林犹太慢性病医院的医生们仔细记录了这种疾病的临床特征和病程。同年，家庭走到一起，互相支持，交流他们在照顾受影响的孩子方面学到的东西，并成立了全国泰-萨克斯和相关疾病协会（NTSAD），这是美国最古老的罕见遗传病患者倡导组织。尽管在临床和病理学上进行了仔细的描述，但TSD的生化病因学尚不清楚，直到奥布莱恩等人描述了β-氨基己糖苷酶A同工酶（各种称为Hex A或β-N-乙酰氨基己糖苷酶αβ）缺乏。[3]的文件。这种酶负责GM 2神经节苷脂的降解，GM 2神经节苷脂是一种复杂的鞘糖脂，在神经系统的细胞膜中特别丰富。β-氨基己糖苷酶A酶缺乏症的发现不仅为受影响婴儿的诊断确认铺平了道路，而且通过Michael Kaback博士的英勇努力，这也导致了从20世纪70年代初开始在全国各地的犹太教堂和社区中心的德系犹太人社区进行携带者筛查。结果，德系犹太人中婴儿TSD的发病率在短短10年内下降了90%以上，TSD成为高危人群中携带者筛查的模式[4]。为了确保载体筛选的质量和准确性，1973年至2006年在卡巴克实验室进行了学术和商业实验室的能力验证，并在NTSAD的监督和支持下在马里兰州大学实验室继续进行。
The GM2 gangliosidoses, Tay-Sachs (TSD), Sandhoff disease (SD) and GM2 activator deficiency are rare, progressive, neurodegenerative lysosomal storage disorders (LSDs) that are uniformly fatal and without effective therapy. The severe infantile form of TSD, originally termed familial amaurotic idiocy, was first described independently in 1899 by British ophthalmologist Waren Tay and New York neurologist Bernard Sachs in infants of Ashkenazi Jewish descent [1]. With the characteristic cherry red macula and multilamellar cytoplasmic bodies in neurons of affected patients, TSD is the prototype for the greater than 70 LSDs resulting from deficiencies in lysosomal hydrolases or transport proteins [2]. The clinical features and course of the disease were carefully chronicled by physicians at the Jewish Chronic Care Hospital in Brooklyn beginning in 1950. That same year families came together to support one another and exchange what they had learned in caring for their affected children and founded the National Tay-Sachs and Allied Diseases Association (NTSAD), the oldest patient advocacy group in the United States for rare genetic diseases. Although carefully described clinically and pathologically, the biochemical etiology of TSD was unknown until a deficiency of the enzyme β-hexosaminidase A isoenzyme (variously known as Hex A or β-N-acetylhexosaminidase αβ) was described by O’Brien et al.[3]. This enzyme is responsible for the degradation of the GM2 ganglioside, a complex glycosphingolipid particularly abundant in cell membranes in the nervous system.The discovery of a deficiency in β-hexosaminidase A enzyme paved the way not only for diagnostic confirmation of affected infants, but through the heroic efforts of Dr. Michael Kaback, also led to carrier screening in the Ashkenazi Jewish community at synagogues and community centers across the country beginning in the early 1970s. As a result, the incidence of infantile TSD among the Ashkenazim decreased by over 90% in just 10 years and TSD became a model for carrier screening among high-risk populations [4]. To assure the quality and accuracy of carrier screening, proficiency testing for academic and commercial laboratories was performed in the Kaback laboratory from 1973 to 2006 and continues at the University of Maryland laboratories with oversight and support from NTSAD.
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影响因子：
5.3
作者：
Chung CG;Park SS;Park JH;Lee SB
通讯作者：
Lee SB
影响因子：
4.5
作者：
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影响因子：
2.5
作者：
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通讯作者：
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影响因子：
5
作者：
Cox, Timothy M.
通讯作者：
Cox, Timothy M.