Connolly A M, Pestronk A, Planer G J, Yue J, Mehta S, Choksi R
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neurology. 1996 Mar;46(3):810-14. doi: 10.1212/wnl.46.3.810.
Congenital muscular dystrophy syndromes are characterized by congenital weakness, contractures, and dystrophic features on muscle biopsy. However, these syndromes are often difficult to diagnose precisely because their clinical and pathologic characteristics are not specific and resemble changes in other myopathies. We examined muscle biopsies from 20 children with a congenital muscular dystrophy syndrome. Disease controls with dystrophies or other myopathies (n=19) and normal individuals (n=15) were studied for comparison. In each biopsy we determined (1) numbers of muscle fibers with alkaline phosphatase (AlkP) staining, (2) numbers of acid phosphatase-(AcP) positive cells, (3) dystrophin levels by immunocytochemistry, and (4) the distribution of merosin and laminin-A staining. A ratio of AcP:AlkP staining was calculated for each biopsy. In nine patients with congenital muscular dystrophy (younger than 4 years of age) with normal dystrophin, the AcP:AlkP ratio was low (0.09 +/- 0.03). In contrast, in Duchenne muscular dystrophy, the AcP:AlkP ratio was 15 times higher (1.6 +/- 0.04, p=0.001). The three children with congetial muscular dystrophy syndromes and reduced dystrophin and one child with facioscapulohumeral dystrophy had AcP:AlkP ratios in the range of Duchenne muscular dystrophy patients (2.4 +/- 1.4). Low Ac:AlkP ratios were related to relative absence of AcP-positive cells. Merosin staining was absent in 5 of the 17 congenital muscular dystrophy biopsies tested. None of the 5 children with merosin-negative but all 12 with merosin-positive stains walked (p=0.0002). We conclude that a pattern of few AcP-positive cells in the setting of numerous AlkP staining muscle fibers has specificity for congenital muscular dystrophy syndromes and provides histopathologic support for the diagnosis. Reduced merosin in muscle predicts more severe weakness and long-term disability.
先天性肌营养不良综合征的特征为先天性肌无力、挛缩以及肌肉活检显示的营养不良特征。然而，这些综合征往往难以精确诊断，因为其临床和病理特征并不特异，与其他肌病的变化相似。我们检查了20例患有先天性肌营养不良综合征儿童的肌肉活检样本。为作比较，研究了患有营养不良或其他肌病的疾病对照者（n = 19）以及正常个体（n = 15）。在每份活检样本中，我们测定了：（1）碱性磷酸酶（AlkP）染色的肌纤维数量；（2）酸性磷酸酶（AcP）阳性细胞的数量；（3）通过免疫细胞化学测定的抗肌萎缩蛋白水平；（4）merosin和层粘连蛋白A染色的分布情况。计算每份活检样本的AcP:AlkP染色比率。在9例年龄小于4岁、抗肌萎缩蛋白正常的先天性肌营养不良患者中，AcP:AlkP比率较低（0.09±0.03）。相比之下，在杜兴氏肌营养不良中，AcP:AlkP比率高出15倍（1.6±0.04，p = 0.001）。3例患有先天性肌营养不良综合征且抗肌萎缩蛋白减少的儿童以及1例面肩肱型肌营养不良患儿的AcP:AlkP比率处于杜兴氏肌营养不良患者的范围（2.4±1.4）。低Ac:AlkP比率与AcP阳性细胞相对缺乏有关。在检测的17份先天性肌营养不良活检样本中，有5份未检测到merosin染色。5例merosin阴性的儿童均不能行走，而12例merosin阳性的儿童均可行走（p = 0.0002）。我们得出结论，在大量AlkP染色的肌纤维背景下，AcP阳性细胞数量少的模式对先天性肌营养不良综合征具有特异性，并为诊断提供了组织病理学支持。肌肉中merosin减少预示着更严重的肌无力和长期残疾。
