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Abstract：
Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is classically caused by a congenital defect in electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). Flavin adenine dinucleotide synthase (FADS) deficiency caused by mutations in FLAD1 was recently reported as a novel riboflavin metabolism disorder resembling MADD. Here, we describe a Japanese boy with FADS deficiency due to a novel mutation (p.R249*) in FLAD1. In the asymptomatic male infant born at full term, newborn screening showed positive results with elevated C5 and C14:1 acylcarnitine levels and an increased C14:1/C2 ratio. Biochemical studies were unremarkable except for lactic acidosis (pH 7.197, lactate 61 mg/dL). A diagnosis of MADD was suspected because of mild abnormalities of the acylcarnitine profile and apparent abnormalities of urinary organic acids, although mutations in the ETFA, ETFB, ETFDH, and riboflavin transporter genes (SLC52A1, SLC52A2, and SLC52A3) were not detected. Administration of riboflavin and L-carnitine was initiated at one month of age based on the diagnosis of \"biochemical MADD\" despite a lack of symptoms. Nevertheless, the acylcarnitine profile was not normalized. Symptoms resembling bulbar palsy, such as vocal cord paralysis and dyspnea with stridor, were present from 3 months of age. At 4 months of age, he became bedridden because of hypoxic-ischemic encephalopathy due to fulminant respiratory failure with aspiration pneumonia. At 2 years and 5 months of age, a homozygous c.745C > T (p.R249*) mutation in the FLAD1 gene was identified, confirming the diagnosis of FADS deficiency. His severe clinical course may be caused by this nonsense mutation associated with poor responsiveness to riboflavin. Persistent lactic acidosis and neuropathy, such as bulbar palsy, may be important for diagnosing FADS deficiency. Although the biochemical findings in FADS deficiency are similar to those in MADD, their clinical symptoms and severity may not be identical.
摘要：
多重酰基辅酶A脱氢酶缺乏症（MADD），也被称为戊二酸血症II型，通常是由电子转移黄素蛋白（ETF）或ETF脱氢酶（ETFDH）的先天性缺陷引起的。最近报道了由FLAD1突变引起的黄素腺嘌呤二核苷酸合酶（FADS）缺陷是一种类似MADD的新型核黄素代谢障碍。这里,我们描述了一个由于新突变而患有FADS缺乏症的日本男孩（p。R249*）在FLAD1中。在足月出生的无症状男婴中，新生儿筛查结果呈阳性,C5和C14:1酰基肉碱水平升高,C14:1/C2比值升高.除乳酸性酸中毒（pH7.197，乳酸61mg/dL）外，生化研究无明显变化。由于酰基肉碱的轻度异常和尿有机酸的明显异常，怀疑诊断为MADD。尽管在ETFA中发生了突变,ETFB,EFDH,未检测到核黄素转运蛋白基因（SLC52A1，SLC52A2和SLC52A3）。尽管没有症状，但根据“生化MADD”的诊断，在一个月大时开始服用核黄素和L-肉碱。然而，酰基肉碱谱未正常化.类似延髓麻痹的症状，如声带麻痹和喘鸣呼吸困难，从3个月大就出现了。在4个月大的时候，他因暴发性呼吸衰竭伴吸入性肺炎导致缺氧缺血性脑病而卧床不起。在2岁零5个月大的时候，纯合c.745C>T（p。确定了FLAD1基因中的R249*）突变，确认FADS缺乏症的诊断。他的严重临床过程可能是由于这种无义突变与对核黄素的反应性差相关。持续性乳酸性酸中毒和神经病,比如球麻痹，可能对诊断FADS缺乏症很重要。尽管FADS缺乏症的生化发现与MADD相似，他们的临床症状和严重程度可能不相同。
