Sewry C A, Taylor J, Anderson L V, Ozawa E, Pogue R, Piccolo F, Bushby K, Dubowitz V, Muntoni F
Department of paediatrics and Neonatal Medicine, MRC Clinical Sciences Centre, Royal postgraduate Medical School, London, UK.
Neuromuscul Disord. 1996 Dec;6(6):467-74. doi: 10.1016/s0960-8966(96)00389-6.
We have identified 12 cases from a group of 45 patients with early onset limb-girdle muscular dystrophy (LGMD), who have a deficiency of the 50 kDa dystrophin-associated glycoprotein, alpha-sarcoglycan. An additional male sibling of one case was also studied clinically. All 12 patients showed a concomitant, but variable, deficiency of alpha-, beta- and gamma-sarcoglycan. None of our patients had a defect in only one component of the sarcoglycan complex. Molecular analysis confirmed that a total absence of one sarcoglycan, associated with reduced expression of the other two, indicates a primary defect. Immunocytochemistry is thus useful for directing molecular studies. Morphological features not usually observed in Xp21 dystrophies were peripheral accumulations of mitochondria, discrete core-like areas, and nemaline rods in one case. Clinical severity and progression was variable between and within families but early loss of ambulation, at or before the age of 12 years, was associated with a total absence of gamma-sarcoglycan. Common clinical features were calf hypertrophy, contractures of the tendo achilles, lumbar lordosis, winging of the scapulae, weak hamstrings and weak neck muscles. All cases had grossly elevated serum creatine kinase. In contrast to patients with Duchenne muscular dystrophy (DMD), our patients with sarcoglycan deficiencies had normal early motor milestones, normal intellect, and good respiratory and cardiac function. Our data confirm that the sarcoglycan complex acts as a unit and that morphological and clinical features can distinguish patients with defects in the sarcoglycans from those with Xp21 dystrophy. In our group of patients prognosis is better than in DMD, but clinical variability makes this difficult to predict in isolated cases.
我们从45例早发型肢带型肌营养不良（LGMD）患者中识别出12例，这些患者缺乏50 kDa抗肌萎缩蛋白相关糖蛋白α - 肌聚糖。还对其中1例患者的1名男性同胞进行了临床研究。所有12例患者均伴有α - 、β - 和γ - 肌聚糖缺乏，但程度各异。我们的患者中没有仅一种肌聚糖复合物成分存在缺陷的情况。分子分析证实，一种肌聚糖完全缺失并伴有另外两种肌聚糖表达降低，表明存在原发性缺陷。因此，免疫细胞化学有助于指导分子研究。在Xp21型肌营养不良中通常未观察到的形态学特征包括线粒体的外周聚集、离散的核心样区域以及1例中的杆状小体。临床严重程度和进展在不同家庭之间以及家庭内部存在差异，但在12岁及之前早期丧失行走能力与γ - 肌聚糖完全缺失有关。常见的临床特征包括小腿肥大、跟腱挛缩、腰椎前凸、肩胛骨翼状畸形、腘绳肌无力和颈部肌肉无力。所有病例的血清肌酸激酶均显著升高。与杜氏肌营养不良（DMD）患者不同，我们的肌聚糖缺乏患者早期运动发育里程碑正常、智力正常，呼吸和心脏功能良好。我们的数据证实肌聚糖复合物作为一个整体发挥作用，并且形态学和临床特征可以将肌聚糖缺陷患者与Xp21型肌营养不良患者区分开来。在我们的患者群体中，预后比DMD患者好，但临床变异性使得在个别病例中难以预测。
