Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment
Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment
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DOI：
10.1007/s10545-010-9242-z
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发表时间：
2011-02-01
影响因子：
4.2
通讯作者：
Waterham, Hans R.
中科院分区：
文献类型：
--
作者：
Bosch, Annet M.;Abeling, Nico G. G. M.;Waterham, Hans R.
我们报告了三个病人（两个兄弟姐妹和一个无关）在婴儿期出现进行性肌无力和膈肌麻痹。代谢研究显示，血浆酰基肉毒碱和尿有机酸谱提示轻度形式的多酰基辅酶A脱氢缺陷（MADD，乙基丙二酸/己二酸综合征）。随后，一个深刻的黄素缺乏症，尽管正常的饮食核黄素摄入量，建立在所有三个孩子的血浆中，表明核黄素转运蛋白缺陷。对这些患者的遗传分析表明，C20 orf 54基因发生突变，该基因编码大鼠核黄素转运蛋白的人类同源物。该基因最近与Brown-Vialetto-货车Laere综合征有关，这是一种罕见的神经系统疾病，可能在婴儿期出现神经功能恶化伴张力减退、呼吸功能不全和早死，或在以后的生活中出现耳聋和进行性脑桥延髓麻痹。补充核黄素迅速改善了我们患者的临床症状以及生化异常，表明高剂量核黄素是Brown-Vialetto-货车Laere综合征以及Fazio Londe综合征的潜在治疗方法，Fazio Londe综合征被认为是没有耳聋的相同疾病实体。
We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafness.