University of Applied Sciences Muenster, Department of Food, Nutrition, and Facilities, Muenster, Germany; University Hospital Muenster, Department of Pediatrics, Muenster, Germany.
University Hospital Muenster, Department of Pediatrics, Muenster, Germany.
Nutrition. 2019 Apr;60:122-128. doi: 10.1016/j.nut.2018.10.014. Epub 2018 Oct 22.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is the most severe disorder of mitochondrial fatty acid β-oxidation. Treatment of this disorder is difficult because the functional loss of the electron transfer flavoprotein makes energy supply from fatty acids impossible. Acetyl-CoA, provided by exogenous ketone bodies such as NaßHB, is the only treatment option in severe cases. Short-term therapy attempts have shown positive results. To our knowledge, no reports exist concerning long-term application of ketone body salts in patients with severe MADD.
This case report is a detailed retrospective metabolic analysis of a boy with severe MADD. Treatment with sodium β-hydroxybutyrate (NaβHB) started 8 d after birth using gradually increasing doses. In the initial phase, metabolic and acid-base parameters were checked multiple times a day. After 8 y of standardized therapy with 16 g NaβHB, substitution with calcium β-hydroxybutyrate (CaβHB) was attempted. In addition to the β-hydroxybutyrate (βHB) supplementation, continuous adjustments were made to the child's nutrition to provide necessary nutrients.
Treatment with βHB salts leads to adverse effects like gastrointestinal discomfort and alkalosis. Measured concentrations of βHB were predominantly at 0.1 mmol/L or below detectable concentration. Nutritional therapy based on amino acid and acylcarnitine profiles is a necessary part of the therapy in MADD.
Therapy with NaβHB is lifesaving in cases of severe MADD but can have significant adverse effects. Supplementation with CaβHB led to gastrointestinal discomfort and had no additional positive clinical effect. The determined tolerable dose of βHB salt for long-term therapy was not high enough for a notable increase of βHB concentrations in blood.
多种酰基辅酶 A 脱氢酶缺乏症（MADD）是线粒体脂肪酸β氧化中最严重的障碍。由于电子传递黄素蛋白的功能丧失，使脂肪酸无法提供能量，因此这种疾病的治疗非常困难。在严重的情况下，乙酰辅酶 A 是唯一的治疗选择，它由外源性酮体如 NaßHB 提供。短期治疗尝试已经显示出积极的结果。据我们所知，尚无关于严重 MADD 患者长期应用酮体盐的报道。
本病例报告详细回顾性分析了一名患有严重 MADD 的男孩。患儿于出生后 8 天开始接受 NaßHB 治疗，剂量逐渐增加。在初始阶段，每天多次检查代谢和酸碱参数。在使用 16 g NaßHB 进行标准化治疗 8 年后，尝试用钙β-羟基丁酸（CaßHB）替代。除了补充β-羟基丁酸（βHB）外，还对患儿的营养进行持续调整，以提供必要的营养。
βHB 盐治疗会导致胃肠道不适和碱中毒等不良反应。测量的βHB 浓度主要为 0.1 mmol/L 或以下，无法检测到浓度。基于氨基酸和酰基肉碱谱的营养治疗是 MADD 治疗的必要组成部分。
在严重 MADD 病例中，NaßHB 治疗是救生的，但会有显著的不良反应。补充 CaßHB 会导致胃肠道不适，且没有额外的临床积极效果。确定的可耐受剂量的βHB 盐用于长期治疗时，其血βHB 浓度的增加并不显著。
