European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)
European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)
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DOI：
10.1007/s00415-019-09539-y
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发表时间：
2020-01-01
影响因子：
6
通讯作者：
Carlier, Robert Y.
中科院分区：
文献类型：
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作者：
Barp, Andrea;Laforet, Pascal;Carlier, Robert Y.
背景：肢带型肌营养不良症R1/2A型(LGMDR1/LGMD2A型)是由于骨骼肌钙依赖性半胱氨酸蛋白酶calain 3缺乏而引起的进行性肌病，是世界上最常见的LGMD类型。在过去的几年里，肌肉磁共振成像(MRI)被提出作为一种工具来识别肌肉参与遗传疾病的模式，并作为肌肉疾病疾病进展的生物标记物。在这项研究中，来自欧洲队列的57名分子确诊的LGMDR1患者(年龄范围为7-78岁)接受了肌肉MRI和全球功能状态评估(Gardner-Medwin和Walton评分以及举臂能力)。结果我们证实了一种特殊的脂肪替代模式，主要累及髋内收肌和腿部肌腱。脊柱伸肌比脊柱旋转肌受到的影响更严重，这与LGMDR1中前凸的发生率高于脊柱侧弯的发生率一致。下肢MRI评分的分级聚类显示，大腿前肌受累可区分疾病进展的不同类别。肌肉脂肪替代的严重程度与CAPN3突变显著相关：尤其是，与两个空等位基因(即，预测缺少Calain-3蛋白)的患者相比，没有或一个“空”等位基因的患者表现出较轻的受累。不出所料，脂肪渗透评分与功能指标密切相关。“假胶原”征象(某些肌肉的中心节育区)与较长和更严重的病程有关。结论骨骼肌MRI对LGMDR1的诊断和临床治疗具有重要意义。
Background Limb girdle muscular dystrophy type R1/2A (LGMDR1/ LGMD2A) is a progressive myopathy caused by deficiency of calpain 3, a calcium-dependent cysteine protease of skeletal muscle, and it represents the most frequent type of LGMD worldwide. In the last few years, muscle magnetic resonance imaging (MRI) has been proposed as a tool for identifying patterns of muscular involvement in genetic disorders and as a biomarker of disease progression in muscle diseases. In this study, 57 molecularly confirmed LGMDR1 patients from a European cohort (age range 7-78 years) underwent muscle MRI and a global evaluation of functional status (Gardner-Medwin and Walton score and ability to raise the arms). Results We confirmed a specific pattern of fatty substitution involving predominantly the hip adductors and hamstrings in lower limbs. Spine extensors were more severely affected than spine rotators, in agreement with higher incidence of lordosis than scoliosis in LGMDR1. Hierarchical clustering of lower limb MRI scores showed that involvement of anterior thigh muscles discriminates between classes of disease progression. Severity of muscle fatty substitution was significantly correlated with CAPN3 mutations: in particular, patients with no or one "null" alleles showed a milder involvement, compared to patients with two null alleles (i.e., predicting absence of calpain- 3 protein). Expectedly, fat infiltration scores strongly correlated with functional measures. The "pseudocollagen" sign (central areas of sparing in some muscle) was associated with longer and more severe disease course. Conclusions We conclude that skeletal muscle MRI represents a useful tool in the diagnostic workup and clinical management of LGMDR1.