The skeletal phenotype of intermediate GM1 gangliosidosis: Clinical, radiographic and densitometric features, and implications for clinical monitoring and intervention
The skeletal phenotype of intermediate GM1 gangliosidosis: Clinical, radiographic and densitometric features, and implications for clinical monitoring and intervention
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DOI：
10.1016/j.bone.2019.115142
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发表时间：
2020-02-01
期刊：
影响因子：
4.1
通讯作者：
Tifft, Cynthia J.
中科院分区：
文献类型：
--
作者：
Ferreira, Carlos R.;Regier, Debra S.;Tifft, Cynthia J.
GM1神经节苷脂沉积症是一种溶酶体储存障碍，由编码溶酶体乳糖苷酶的GLB1突变引起。这种疾病是一个连续的过程，从严重的婴儿型神经功能迅速下降到慢性成人型，没有生命限制。中间型或2型又可进一步分为婴儿期晚期和幼年型。晚期婴幼儿和青少年患者骨骼结局的频率和严重程度尚未确定。我们的目标是描述中度GM1神经节苷脂沉积症患者的放射学骨骼异常、骨密度(BMD)和骨折频率。作为正在进行的自然历史研究的一部分，我们评估了13名婴儿晚期患者和21名青少年患者。晚期婴儿和青少年患者从症状出现到诊断的平均时间分别为1.9年和6.3年。所有晚期婴幼儿患者均有齿状突发育不良和梨形椎体，其发生率与幼年型患者有显著差异(分别为无和14%)。青少年患者椎体终板不规则(15/21)，终板中心凹陷(10/21)，椎体呈方形扁平(10/21)；腰椎、股骨颈和全髋部骨密度显著降低(分别为2.1、2.2和1.8Z分)。腰椎骨密度在19岁达到峰值，前臂远端骨密度在30岁达到峰值。尽管骨密度低，但没有患者出现骨折。我们已经证明，所有晚期婴儿患者都有不同程度的齿状突发育不良，这表明有必要进行颈椎评估，特别是在麻醉前，而青少年患者有不同的骨骼受累，通常影响日常生活能力。2型神经节苷脂沉积症患者的骨骼异常既是诊断的早期指征，也需要监测和管理，以确保尽可能高的生活质量。
GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1 encoding a lysosomal lactosidase. This disease is a continuum from the severe infantile form with rapid neurological decline to the chronic adult form, which is not life-limiting. The intermediate or type 2 form can be further classified into late infantile and juvenile forms. The frequency and severity of skeletal outcomes in late infantile and juvenile patients have not been characterized. Our goals are to describe the radiological skeletal abnormalities, bone mineral density (BMD), and frequency of fractures in patients with intermediate GM1 gangliosidosis. We evaluated 13 late infantile and 21 juvenile patients as part of an ongoing natural history study. Average time from onset of symptoms to diagnosis was 1.9 and 6.3 years for late infantile and juvenile patients, respectively. All late infantile patients had odontoid hypoplasia and pear-shaped vertebral bodies, the frequency of which was significantly different than in patients with juvenile disease (none and 14%, respectively). Juvenile patients had irregular endplates of the vertebral bodies (15/21), central indentation of endplates (10/21), and squared and flat vertebral bodies (10/21); all allowed radiographic differentiation from late infantile patients. Lumbar spine, femoral neck, and total hip BMD were significantly decreased (2.1, 2.2, and 1.8 Z-scores respectively). Lumbar spine BMD peaked at 19 years, while distal forearm BMD peaked at 30 years. Despite low BMD, no patients exhibited fractures. We have demonstrated that all late infantile patients have some degree of odontoid hypoplasia suggesting the need for cervical spine evaluation particularly prior to anesthesia, whereas juvenile patients had variable skeletal involvement often affecting activities of daily living. Type 2 GM1 gangliosidosis patients have skeletal abnormalities that are both an early indication of their diagnosis, and require monitoring and management to ensure the highest possible quality of life.