Department of Neurology, Peking University People's Hospital, Beijing 100044, China.
Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
Chin Med J (Engl). 2019 Feb 5;132(3):275-284. doi: 10.1097/CM9.0000000000000032.
Late-onset multiple acyl-coA dehydrogenase deficiency (MADD) is an autosomal recessive inherited metabolic disorder. It is still unclear about the muscle magnetic resonance image (MRI) pattern of the distal lower limb pre- and post-treatment in patients with late-onset MADD. This study described the clinical and genetic findings in a cohort of patients with late-onset MADD, and aimed to characterize the MRI pattern of the lower limbs.
Clinical data were retrospectively collected from clinic centers of Peking University People's Hospital between February 2014 and February 2018. Muscle biopsy, blood acylcarnitines, and urine organic acids profiles, and genetic analysis were conducted to establish the diagnosis of MADD in 25 patients. Muscle MRI of the thigh and leg were performed in all patients before treatment. Eight patients received MRI re-examinations after treatment.
All patients presented with muscle weakness or exercise intolerance associated with variants in the electron transfer flavoprotein dehydrogenase gene. Muscle MRI showed a sign of both edema-like change and fat infiltration selectively involving in the soleus (SO) but sparing of the gastrocnemius (GA) in the leg. Similar sign of selective involvement of the biceps femoris longus (BFL) but sparing of the semitendinosus (ST) was observed in the thigh. The sensitivity and specificity of the combination of either "SO+/GA-" sign or "BFL+/ST-" sign for the diagnosis of late-onset MADD were 80.0% and 83.5%, respectively. Logistic regression model supported the findings. The edema-like change in the SO and BFL muscles were quickly recovered at 1 month after treatment, and the clinical symptom was also relieved.
This study expands the clinical and genetic spectrums of late-onset MADD. Muscle MRI shows a distinct pattern in the lower limb of patients with late-onset MADD. The dynamic change of edema-like change in the affected muscles might be a potential biomarker of treatment response.
迟发性多种酰基辅酶 A 脱氢酶缺乏症（MADD）是一种常染色体隐性遗传性代谢紊乱。目前尚不清楚迟发性 MADD 患者治疗前后下肢远端肌肉磁共振成像（MRI）的表现。本研究描述了一组迟发性 MADD 患者的临床和遗传发现，并旨在描述下肢 MRI 表现。
回顾性收集 2014 年 2 月至 2018 年 2 月期间北京大学人民医院临床中心的临床资料。对 25 例患者进行肌肉活检、血酰基肉碱和尿有机酸谱及基因分析，以确立 MADD 的诊断。所有患者均在治疗前进行大腿和小腿肌肉 MRI 检查。8 例患者在治疗后接受 MRI 复查。
所有患者均表现为肌无力或运动不耐受，伴有电子转移黄素蛋白脱氢酶基因变异。肌肉 MRI 显示，腿部的比目鱼肌（SO）出现水肿样改变和脂肪浸润，而腓肠肌（GA）不受累；大腿的股二头肌长头（BFL）也出现类似选择性受累而半腱肌（ST）不受累的征象。“SO+/GA-”或“BFL+/ST-”征象联合诊断迟发性 MADD 的敏感性和特异性分别为 80.0%和 83.5%。Logistic 回归模型支持这些发现。治疗后 1 个月，SO 和 BFL 肌肉的水肿样改变迅速恢复，临床症状也得到缓解。
本研究扩大了迟发性 MADD 的临床和遗传谱。迟发性 MADD 患者下肢肌肉 MRI 显示出独特的表现。受累肌肉水肿样改变的动态变化可能是治疗反应的潜在生物标志物。
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