Rodrigues Andresa De Santi, Kiyomoto Beatriz H, Oliveira Acary S B, Gabbai Alberto A, Schmidt Beny, Tengan Celia H
Department of Neurology and Neurosurgery, Clinical Neurology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
J Neurol Sci. 2008 Jan 15;264(1-2):182-6. doi: 10.1016/j.jns.2007.08.002. Epub 2007 Sep 12.
Biochemical defects in the respiratory chain are mostly associated with deficiencies in Complexes I, III and IV, caused by nuclear or mitochondrial DNA mutations. Combined defects including Complex II have been reported very rarely and have muscular symptoms as the main manifestation, including muscle weakness, exercise intolerance and myoglobinuria. We report a patient with a fatal progressive myopathy and muscle biopsy showing diffuse reduction in succinate dehydrogenase activity, ragged red fibers and intense lipid accumulation. Cytochrome c oxidase (COX) histochemistry demonstrated 30% of fibers with increased subsarcolemmal staining while 27% were COX negative. Western blotting analysis showed reduction in the expression of the 39 kDa subunit of Complex I, subunit II of Complex IV and the 70 kDa subunit of Complex II. Our findings suggest that the patient had a complex pattern of mitochondrial dysfunction affecting multiple respiratory chain complexes (I, II and IV) and fatty acid metabolism. This report adds a new histological pattern associated to combined deficiencies of respiratory chain with involvement of Complex II and shows that this disease may be fatal with a rapid progression.
呼吸链中的生化缺陷大多与由核或线粒体DNA突变引起的复合体I、III和IV的缺陷有关。包括复合体II在内的联合缺陷报道非常罕见，主要表现为肌肉症状，包括肌肉无力、运动不耐受和肌红蛋白尿。我们报告了一名患有致命性进行性肌病的患者，肌肉活检显示琥珀酸脱氢酶活性弥漫性降低、破碎红纤维和大量脂质蓄积。细胞色素c氧化酶（COX）组织化学显示30%的纤维肌膜下染色增加，而27%的纤维COX阴性。蛋白质免疫印迹分析显示复合体I的39 kDa亚基、复合体IV的亚基II和复合体II的70 kDa亚基表达减少。我们的研究结果表明，该患者存在影响多个呼吸链复合体（I、II和IV）和脂肪酸代谢的复杂线粒体功能障碍模式。本报告增加了一种与呼吸链联合缺陷伴复合体II受累相关的新组织学模式，并表明这种疾病可能进展迅速且致命。
