Riboflavin‐responsive multiple acyl‐CoA dehydrogenase deficiency: A frequent condition in the southern Chinese population

Abstract

AbstractMultiple acyl‐CoA dehydrogenase deficiency (MADD) is caused by the recessive mutations in any of ETFA, ETFB and ETFDH, respectively, encoding electron transfer flavoprotein (ETF)‐α, ETF‐β and ETF‐ubiquinone oxidoreductase (ETF‐QO), resulting in defects in the transfer of high‐energy electrons from acyl‐CoA dehydrogenases in mitochondria and leading to dysfunction of all ETF‐dependent acyl‐CoA dehydrogenases. MADD seems to be very rare, at least in the Japanese population, but not among the southern Chinese population because of the presence of the common c.250G>A (p.Ala84Thr) mutation in ETFDH, with an estimated carrier frequency of approximately 1%. This mutation was originally identified in MADD patients in Taiwan; but later, several reports of the same mutation, including those from southern China, ensued this. So far, this mutation has not been identified in any other population, except for only a few patients in northern China, probably as a result of migration. High‐dose riboflavin supplementation therapy has been shown to be efficacious in MADD patients with certain ETFDH mutations, including p.Ala84Thr, suggesting that MADD in most southern Chinese patients might be treatable. Therefore, the possibility of MADD should be highly suspected in southern Chinese patients with relevant clinical manifestations.