D'Amico Adele, Bertini Enrico
Molecular Medicine and Unit of Neuromuscular and Neurodegenerative Diseases, IRCCS-Children's Hospital Bambino Gesù, Rome, Italy.
Handb Clin Neurol. 2013;113:1437-55. doi: 10.1016/B978-0-444-59565-2.00013-7.
Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney.
先天性代谢缺陷可能会影响肌肉和周围神经。异常情况涉及线粒体以及其他亚细胞器，如与细胞区室周转和再循环相关的过氧化物酶体和溶酶体。可治疗的病因包括导致进行性神经病变的β氧化缺陷；丙酮酸脱氢酶缺乏症、卟啉症或维生素B12缺乏症，可引起复发性神经病变或类似吉兰 - 巴雷综合征的急性运动功能缺损。另一方面，溶酶体疾病（黏多糖贮积症、戈谢病和法布里病）、线粒体疾病（线粒体或核突变或线粒体DNA耗竭）、过氧化物酶体疾病（肾上腺脑白质营养不良、雷夫叙姆病、固醇载体蛋白2缺乏症、脑腱性黄瘤病、α - 甲基酰基辅酶A消旋酶缺乏症）是多系统疾病，还累及心脏、肝脏、大脑、视网膜和肾脏。大多数代谢性肌病的病理生理学与能量产生受损或活性氧（ROS）异常产生有关。主要症状为运动不耐受，伴有肌痛、痉挛和复发性肌红蛋白尿，或肢体无力伴血清肌酸激酶升高。肉碱棕榈酰转移酶缺乏症，其次是酸性麦芽糖酶缺乏症和脂素缺乏症，是孤立性横纹肌溶解最常见的原因。代谢性肌病常与神经肌肉外疾病相关，特别是累及心脏、肝脏、大脑、视网膜、皮肤和肾脏。
