Gramer Gwendolyn, Hoffmann Georg F, Hennermann Julia B
University Hospital Heidelberg, Center for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Metabolic Medicine, Heidelberg, Germany.
University Medical Center Mainz, Villa Metabolica, Department of Pediatric and Adolescent Medicine, Mainz, Germany.
Mol Genet Metab Rep. 2021 Mar 6;27:100738. doi: 10.1016/j.ymgmr.2021.100738. eCollection 2021 Jun.
In infancy multiple acyl-CoA dehydrogenase deficiency (MADD) is commonly a severe inherited metabolic disease caused by genetic defects in electron transfer flavoprotein (ETF) or ETF ubiquinone oxidoreductase. Both enzymes require flavin adenine dinucleotide (FAD) as a cofactor. Riboflavin (vitamin B) is a precursor in the synthesis of FAD. MADD can be detected by newborn screening (NBS) based on elevation of multiple acylcarnitines.
We present the results of two children whose NBS results and subsequent confirmatory testing resulted in a suspected diagnosis of MADD. In parallel in both children vitamin B deficiency was detected.
Biochemical profiles normalized rapidly in both children under supplementation with riboflavin. After extensive work-up of both cases including molecular genetic studies there was no indication of MADD. Vitamin B deficiency in both children was caused by maternal vitamin B deficiency and was rapidly corrected by oral supplementation with vitamin B or (partial) formula feeding. As both vitamin B and riboflavin have similar food sources we postulate that in these cases positive NBS for MADD was caused by combined maternal vitamin B deficiencies.
The differential diagnosis of maternally caused vitamin B deficiencies should be considered in children with abnormal NBS results for MADD, especially in the presence of normal molecular genetic analysis or in case of associated findings of other maternal vitamin B deficiencies like vitamin B or folic acid deficiency.
在婴儿期，多种酰基辅酶A脱氢酶缺乏症（MADD）通常是一种严重的遗传性代谢疾病，由电子传递黄素蛋白（ETF）或ETF泛醌氧化还原酶的基因缺陷引起。这两种酶都需要黄素腺嘌呤二核苷酸（FAD）作为辅助因子。核黄素（维生素B）是FAD合成的前体。基于多种酰基肉碱水平升高，MADD可通过新生儿筛查（NBS）检测出来。
我们展示了两名儿童的结果，他们的NBS结果及随后的确诊检测导致疑似MADD诊断。同时，在这两名儿童中均检测到维生素B缺乏。
在补充核黄素后，两名儿童的生化指标均迅速恢复正常。在对这两个病例进行包括分子遗传学研究在内的广泛检查后，没有发现MADD的迹象。两名儿童的维生素B缺乏均由母亲维生素B缺乏引起，通过口服补充维生素B或（部分）配方奶喂养可迅速纠正。由于维生素B和核黄素具有相似的食物来源，我们推测在这些病例中，MADD的NBS阳性是由母亲维生素B联合缺乏导致的。
对于MADD的NBS结果异常的儿童，尤其是在分子遗传学分析正常或存在其他母亲维生素B缺乏（如维生素B或叶酸缺乏）相关表现的情况下，应考虑母亲所致维生素B缺乏的鉴别诊断。
