Department of Pediatrics, University of Amsterdam, Amsterdam, the Netherlands.
Pediatr Res. 2010 Mar;67(3):304-8. doi: 10.1203/PDR.0b013e3181cbd57b.
Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inborn error, biochemically characterized by increased plasma butyrylcarnitine (C4-C) concentration and increased ethylmalonic acid (EMA) excretion and caused by rare mutations and/or common gene variants in the SCAD encoding gene. Although its clinical relevance is not clear, SCADD is included in most US newborn screening programs. Riboflavin, the precursor of flavin adenine dinucleotide (FAD, cofactor), might be effective for treating SCADD. We assessed the FAD status and evaluated the effects of riboflavin treatment in a prospective open-label cohort study involving 16 patients with SCADD, subdivided into mutation/mutation (mut/mut), mutation/variant (mut/var), and variant/variant (var/var) genotype groups. Blood FAD levels were normal in all patients before therapy, but significantly lower in the mut/var and var/var groups compared with the mut/mut group. Riboflavin treatment resulted in a decrease in EMA excretion in the mut/var group and in a subjective clinical improvement in four patients from this group. However, this improvement persisted after stopping treatment. These results indicate that high-dose riboflavin treatment may improve the biochemical features of SCADD, at least in patients with a mut/var genotype and low FAD levels. As our study could not demonstrate a clinically relevant effect of riboflavin, general use of riboflavin cannot be recommended.
短链酰基辅酶 A 脱氢酶缺乏症（SCADD）是一种先天性缺陷，其生化特征为血浆丁酰肉碱（C4-C）浓度升高和乙基丙二酸（EMA）排泄增加，由 SCAD 编码基因中的罕见突变和/或常见基因变异引起。尽管其临床相关性尚不清楚，但 SCADD 已被纳入大多数美国新生儿筛查计划。核黄素，黄素腺嘌呤二核苷酸（FAD，辅因子）的前体，可能对治疗 SCADD 有效。我们评估了 FAD 状态，并在一项涉及 16 例 SCADD 患者的前瞻性开放标签队列研究中评估了核黄素治疗的效果，这些患者分为突变/突变（mut/mut）、突变/变异（mut/var）和变异/变异（var/var）基因型组。在治疗前，所有患者的血液 FAD 水平均正常，但 mut/var 和 var/var 组明显低于 mut/mut 组。核黄素治疗可降低 mut/var 组的 EMA 排泄量，并使该组的四名患者主观临床症状改善。然而，在停止治疗后，这种改善仍然存在。这些结果表明，高剂量核黄素治疗可能改善 SCADD 的生化特征，至少在 mut/var 基因型和低 FAD 水平的患者中如此。由于我们的研究未能证明核黄素具有临床相关的疗效，因此不能推荐普遍使用核黄素。
