Clinical course correlates poorly with muscle pathology in nemaline myopathy
Clinical course correlates poorly with muscle pathology in nemaline myopathy
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DOI：
10.1212/01.wnl.0000046585.81304.bc
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发表时间：
2003-02-25
期刊：
影响因子：
9.9
通讯作者：
Beggs, AH
中科院分区：
文献类型：
--
作者：
Ryan, MM;Ilkovski, B;Beggs, AH
目的：报告124例澳大利亚和北美原发性线状体肌病的病理学表现。研究方法：回顾了124例澳大利亚和北美原发性线状体肌病患者的164例肌肉活检结果，包括19例α-肌动蛋白（ACTA 1）突变所致线状体肌病患者和3例α-原肌球蛋白（SLOW）（TPM 3）突变所致线状体肌病患者的活检结果。对于每根纤维的每个活检杆数量，记录了带杆纤维的百分比、杆的纤维类型分布以及核内杆的存在或不存在。结果：所有骨骼肌中均存在杆状细胞，诊断在所有年龄段均可行。大多数活组织检查中，超过50%的纤维中含有线状体，尽管仅在10例患者的电子显微镜下观察到杆状体。棒数量和定位与临床严重程度相关性较差。常见的发现包括内部核和增加的纤维大小的变化，1型纤维优势和萎缩，和改变表达的纤维类型特异性蛋白。显著的肌节破坏、糖原沉积增加和核内杆与更严重的临床表型相关。连续活检显示纤维大小逐渐变化，随着时间的推移，杆的数量增加。病理结果在多个受累成员的家庭中差异很大。结论：在与骨骼α-肌动蛋白突变相关的线状体肌病中，非常多的线状体、糖原积累和显著的肌节破坏是常见的。由于α-原肌球蛋白（SLOW）突变引起的线状肌病的特征是1型纤维中优先形成杆和萎缩。线状体肌病的光镜特征与病程关系不大。电子显微镜检查可能与疾病的严重程度和基因型更好地相关。
Objective: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy. Methods: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to alpha-actin (ACTA1) mutations and three with mutations in alpha-tropomyosin(SLOW) (TPM3). For each biopsy rod number per fiber, percentage of fibers with rods, fiber-type distribution of rods, and presence or absence of intranuclear rods were documented. Results: Rods were present in all skeletal muscles and diagnosis was possible at all ages. Most biopsies contained nemaline bodies in more than 50% of fibers, although rods were seen only on electron microscopy in 10 patients. Rod numbers and localization correlated poorly with clinical severity. Frequent findings included internal nuclei and increased fiber size variation, type 1 fiber predominance and atrophy, and altered expression of fiber type specific proteins. Marked sarcomeric disruption, increased glycogen deposition, and intranuclear rods were associated with more severe clinical phenotypes. Serial biopsies showed progressive fiber size variation and increasing numbers of rods with time. Pathologic findings varied widely in families with multiple affected members. Conclusions: Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal alpha-actin. Nemaline myopathy due to mutations in alpha-tropomyosin(SLOW) was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype.