Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Genet Med. 2020 May;22(5):908-916. doi: 10.1038/s41436-019-0739-z. Epub 2020 Jan 6.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a life-threatening, ultrarare inborn error of metabolism. Case reports described successful D,L-3-hydroxybutyrate (D,L-3-HB) treatment in severely affected MADD patients, but systematic data on efficacy and safety is lacking.
A systematic literature review and an international, retrospective cohort study on clinical presentation, D,L-3-HB treatment method, and outcome in MADD(-like) patients.
Our study summarizes 23 MADD(-like) patients, including 14 new cases. Median age at clinical onset was two months (interquartile range [IQR]: 8 months). Median age at starting D,L-3-HB was seven months (IQR: 4.5 years). D,L-3-HB doses ranged between 100 and 2600 mg/kg/day. Clinical improvement was reported in 16 patients (70%) for cardiomyopathy, leukodystrophy, liver symptoms, muscle symptoms, and/or respiratory failure. D,L-3-HB appeared not effective for neuropathy. Survival appeared longer upon D,L-3-HB compared with historical controls. Median time until first clinical improvement was one month, and ranged up to six months. Reported side effects included abdominal pain, constipation, dehydration, diarrhea, and vomiting/nausea. Median D,L-3-HB treatment duration was two years (IQR: 6 years). D,L-3-HB treatment was discontinued in 12 patients (52%).
The strength of the current study is the international pooling of data demonstrating that D,L-3-HB treatment can be effective and safe in MADD(-like) patients.
多种酰基辅酶 A 脱氢酶缺乏症（MADD）是一种危及生命的、极罕见的先天性代谢缺陷。病例报告描述了严重 MADD 患者接受 D,L-3-羟基丁酸（D,L-3-HB）治疗的成功案例，但缺乏关于疗效和安全性的系统数据。
系统文献回顾和一项国际回顾性队列研究，评估了 MADD（类似）患者的临床表现、D,L-3-HB 治疗方法和结局。
我们的研究总结了 23 例 MADD（类似）患者，包括 14 例新病例。临床发病的中位年龄为两个月（四分位距 [IQR]：8 个月）。开始 D,L-3-HB 治疗的中位年龄为七个月（IQR：4.5 岁）。D,L-3-HB 剂量范围为 100 至 2600mg/kg/天。16 例（70%）患者的心肌病、白质营养不良、肝脏症状、肌肉症状和/或呼吸衰竭得到改善。D,L-3-HB 对神经病无效。与历史对照相比，D,L-3-HB 治疗后患者的生存率似乎更长。首次临床改善的中位时间为一个月，范围可达六个月。报告的副作用包括腹痛、便秘、脱水、腹泻和呕吐/恶心。D,L-3-HB 治疗的中位持续时间为两年（IQR：6 年）。12 例患者（52%）停止了 D,L-3-HB 治疗。
本研究的优势在于国际数据的汇集，表明 D,L-3-HB 治疗对 MADD（类似）患者是有效且安全的。
