Ryan M M, Ilkovski B, Strickland C D, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield L K, De Girolami U, Iannaccone S T, Laing N G, North K N, Beggs A H
Department of Neurology, Genetics Division, Children's Hospital, Boston, MA 02115, USA.
Neurology. 2003 Feb 25;60(4):665-73. doi: 10.1212/01.wnl.0000046585.81304.bc.
To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy.
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.
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.
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.
报告124例澳大利亚和北美原发性杆状体肌病患者的病理检查结果。
回顾了124例澳大利亚和北美原发性杆状体肌病患者的164份肌肉活检结果，其中包括19例因α-肌动蛋白（ACTA1）突变导致的杆状体肌病患者和3例因α-原肌球蛋白（慢型）（TPM3）突变导致的杆状体肌病患者的活检结果。记录每份活检标本中每根肌纤维的杆状体数量、有杆状体的肌纤维百分比、杆状体的纤维类型分布以及核内杆状体的有无。
所有骨骼肌均存在杆状体，各年龄段均可作出诊断。大多数活检标本中超过50%的肌纤维含有杆状体小体，不过只有10例患者在电子显微镜下才能看到杆状体。杆状体数量和定位与临床严重程度的相关性较差。常见表现包括肌核内移和肌纤维大小变异增加、I型纤维占优势和萎缩，以及纤维类型特异性蛋白表达改变。明显的肌节破坏、糖原沉积增加和核内杆状体与更严重的临床表型相关。连续活检显示，随着时间推移，肌纤维大小变异逐渐增加，杆状体数量增多。在有多个患病成员的家族中，病理检查结果差异很大。
在与骨骼肌α-肌动蛋白突变相关的杆状体肌病中，大量的杆状体小体、糖原积累和明显的肌节破坏很常见。因α-原肌球蛋白（慢型）突变导致的杆状体肌病的特征是I型纤维中优先形成杆状体并出现萎缩。杆状体肌病的光镜特征与病程的相关性较差。电子显微镜检查结果可能与疾病严重程度和基因型的相关性更好。
