Department of Endocrinology and Diabetes, Royal Perth Hospital, Perth, Western Australia, Australia
School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.
BMJ Case Rep. 2023 May 22;16(5):e252668. doi: 10.1136/bcr-2022-252668.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism that results in impairment of mitochondrial β-oxidation of fatty acids. It is inherited in an autosomal recessive manner and impairs electron transfer in the electron transport chain. The clinical manifestations of MADD are highly variable and include exercise intolerance, myopathy, cardiomyopathy, encephalopathy, coma and death. Early-onset MADD is often associated with a high mortality with significant number of patients presenting with severe metabolic acidosis, non-ketotic hypoglycaemia and/or hyperammonaemic presentations. While late-onset MADD is suggested to have a lower mortality, the severe encephalopathic presentations may well be under-reported as a diagnosis of MADD may not be considered.MADD is treatable with riboflavin and appropriate nutrition with a focus on prevention and early management of metabolic decompensation. The neonatal phenotype differs significantly from late-onset MADD, where diagnosis may be delayed due to heterogeneity in clinical features, atypical presentation and confounding comorbidities, together with lower awareness among physicians.This report describes a woman in her 30s who presented with acute-onset ataxia, confusion and hyperammonaemic encephalopathy requiring intubation. Subsequent biochemical investigation revealed a diagnosis of MADD. At present, there are no national guidelines in Australia for the management of MADD. This case highlights the investigation and treatment of late-onset MADD.
多种酰基辅酶 A 脱氢酶缺乏症(MADD)是一种罕见的先天性代谢缺陷,导致脂肪酸的线粒体β氧化受损。它以常染色体隐性遗传方式遗传,并损害电子传递链中的电子转移。MADD 的临床表现高度可变,包括运动不耐受、肌病、心肌病、脑病、昏迷和死亡。早发性 MADD 常伴有高死亡率,许多患者表现出严重的代谢性酸中毒、非酮症低血糖和/或高氨血症。虽然晚发性 MADD 的死亡率较低,但严重的脑病表现可能被低估,因为 MADD 的诊断可能未被考虑。MADD 可通过核黄素和适当的营养治疗,重点是预防和早期管理代谢失代偿。新生儿表型与晚发性 MADD 有显著差异,由于临床特征的异质性、非典型表现和混杂的合并症,以及医生的认识水平较低,可能会导致诊断延迟。本报告描述了一位 30 多岁的女性,她出现急性发作的共济失调、意识混乱和高氨血症性脑病,需要插管。随后的生化检查提示 MADD 诊断。目前,澳大利亚没有关于 MADD 管理的国家指南。本病例强调了对晚发性 MADD 的调查和治疗。