背景:代谢性肌病(MM)是一组异质性的遗传疾病,会影响静息过程中与能量产生有关的代谢途径,运动和生理压力(发烧,禁食,...).糖酵解/糖原分解途径的损害,脂肪酸运输/氧化或线粒体呼吸链中主要存在运动不耐受,肌痛,弱点,抽筋,或者横纹肌溶解症.根据病因,可以通过新生儿筛查来诊断,症状前或在一组临床表现中,高度怀疑是重要的。
方法:临床回顾性描述性研究,生物化学,以及确诊为MM的患者的分子特征,随后是2009年至2022年里斯本中央大学中央医院遗传代谢疾病参考中心的多学科团队。
结果:包括23例MM患者:9例(39%)糖原贮积性疾病(7例McArdle和2例Pompe),7(30%)脂肪酸氧化障碍(3CPT2,3LCHAD和1MAD缺乏),6(26%)线粒体疾病,伴有明显的肌肉受累(2Pearson,1KearnsSayre,1个VARS2、1个SUCLA2和1个MT-TL1缺陷),和1肌腺苷酸脱氨酶缺乏症。年龄从15个月到35岁不等。18例(78%)患者通过临床症状确诊,3例通过新生儿筛查(LCHAD),2例无症状(1例Pompe和1例McArdle)。常见的症状是疾病或运动引发的横纹肌溶解12(52%),疲劳11(48%),运动不耐受10(43%),和肌痛9(43%)。8例(35%)患者(LCHAD和线粒体)有多系统受累。在20名(87%)患者中,通过生化和/或基因分析和肌肉活检3(McArdle)证实诊断.
结论:MM是一组异质性疾病,但仔细的病史可以指导生化途径和其他病因之间的鉴别诊断.如今,分子检测已成为诊断确认的有力工具,超越肌肉活检在大多数情况下。准确的诊断对于确定谁可能从特定的治疗选择中受益非常重要。如酶替代疗法,限制饮食,应急机制和辅因子。所有患者都受益于适当的生活方式改变,个性化运动处方,营养干预,和遗传咨询。
BACKGROUND: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important.
METHODS: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022.
RESULTS: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy.
CONCLUSIONS: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.