Zhao Yunhua, Li Zhichao, Cui Lili, Chen Jun, Zhong Wangtao
Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Front Pediatr. 2025 Jul 2;13:1513288. doi: 10.3389/fped.2025.1513288. eCollection 2025.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder characterized by dysfunctional acyl-CoA dehydrogenases, leading to lipid accumulation in various tissues, including skeletal muscles, liver, and cardiac muscles, etc. Late-onset MADD presents with progressive muscular symptoms (muscle weakness, atrophy, and myalgia) and even multisystem disorders (metabolic encephalopathy, dilated cardiomyopathy, liver failure, acute kidney injury, respiratory failure, and cardiac arrest). Over the past decade, only one case of childhood late-onset MADD with severe multi-organ failure has been reported.
We report a 15-year-old girl with worsening muscle weakness, atrophy, myalgia, hepatic insufficiency, respiratory failure and even cardiac arrest. Laboratory tests showed significantly elevated levels of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). A weakly positive serum small ubiquitin-like modifier 1 activating enzyme (SAE1) antibody suggested antibody-negative polymyositis (PM), but serum acylcarnitine analysis indicated increased concentrations of various acylcarnitines, while urine organic acids was normal. Muscle biopsy revealed significant lipid deposition within muscle fibers pointing to the diagnosis of lipid storage myopathy (LSM). Genetic testing identified a homozygous c.250G>A (p.Ala84Thr) mutation in electron transfer flavoprotein dehydrogenase (ETFDH), inherited from her parents. Although this pathogenic mutation is known in MADD, it has not been associated with adolescent late-onset MADD with severe multi-organ failure. After riboflavin supplementation, the patient regained mobility without ventilator support, with no recurrence of myopathic symptoms upon follow-up.
MADD is a rare but treatable disease and its diagnosis is challenging due to its high clinical heterogeneity. Therefore, based on clinical, biochemical and pathological findings, gene analysis is critical for accurate diagnosis and clinical intervention, as riboflavin supplementation has shown lifesaving therapeutic benefit even in adolescent late-onset MADD with severe multi-organ failure.
多种酰基辅酶A脱氢酶缺乏症（MADD）是一种罕见的常染色体隐性疾病，其特征为酰基辅酶A脱氢酶功能异常，导致脂质在包括骨骼肌、肝脏和心肌等多种组织中蓄积。迟发型MADD表现为进行性肌肉症状（肌无力、萎缩和肌痛），甚至多系统疾病（代谢性脑病、扩张型心肌病、肝功能衰竭、急性肾损伤、呼吸衰竭和心脏骤停）。在过去十年中，仅报道过一例患有严重多器官功能衰竭的儿童迟发型MADD病例。
我们报告一名15岁女孩，出现肌无力、萎缩、肌痛加重，伴有肝功能不全、呼吸衰竭甚至心脏骤停。实验室检查显示肌酸激酶MB同工酶（CK-MB）和乳酸脱氢酶（LDH）水平显著升高。血清小泛素样修饰物1激活酶（SAE1）抗体弱阳性提示抗体阴性多发性肌炎（PM），但血清酰基肉碱分析表明多种酰基肉碱浓度增加，而尿有机酸正常。肌肉活检显示肌纤维内有大量脂质沉积，提示诊断为脂质贮积性肌病（LSM）。基因检测在电子传递黄素蛋白脱氢酶（ETFDH）中鉴定出一个纯合的c.250G>A（p.Ala84Thr）突变，该突变遗传自她的父母。虽然此致病突变在MADD中已知，但它与伴有严重多器官功能衰竭的青少年迟发型MADD无关。补充核黄素后，患者在无需呼吸机支持的情况下恢复了活动能力，随访时肌病症状未复发。
MADD是一种罕见但可治疗的疾病，由于其高度的临床异质性，其诊断具有挑战性。因此，基于临床、生化和病理结果，基因分析对于准确诊断和临床干预至关重要，因为补充核黄素即使在伴有严重多器官功能衰竭的青少年迟发型MADD中也显示出挽救生命的治疗益处。
