Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.
Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.
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DOI：
10.1007/s10545-010-9246-8
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Gibson, K. Michael
中科院分区：
文献类型：
--
作者：
Wolfe, Lynne A.;He, Miao;Vockley, Jerry;Payne, Nicole;Rhead, William;Hoppel, Charles;Spector, Elaine;Gernert, Kim;Gibson, K. Michael
我们描述一个22岁的男性，在4个月大的急性疾病期间出现严重的低血糖和嗜睡，随后生长和发育正常。4岁时出现反复呕吐，伴有轻度高氨血症和脱水，需要频繁住院治疗。根据生化结果，怀疑为II型戊二酸尿症，并使用玉米淀粉、肉碱和核黄素补充剂进行治疗。他在4-12岁期间没有经历代谢危机。他经历了反复呕吐，轻度高氨血症，以及与急性疾病和生长激增相关的全身虚弱。18岁时，他出现了运动耐受性和近端肌肉无力，导致在骨骼肌和肝脏中发现了多种酰辅酶脱氢酶和复杂的II/III缺陷。随后对ETFDH基因的分子鉴定发现了新的杂合突变，p.G274X：C.820G>；T(外显子7)和p.P534L：c.1601 C>；T(外显子12)，后者位于铁硫簇内，预计会影响ETFDH的泛醌还原酶活性和ETF与ETFDH的对接。我们的案例支持ETFDH与其他酶伙伴之间结构相互作用的概念，并表明ETF与ETFDH结合后的构象变化可能在ETFDH与II/III超复合体的形成中发挥关键作用。
We describe a 22-year-old male who developed severe hypoglycemia and lethargy during an acute illness at 4 months of age and subsequently grew and developed normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II was suspected based upon biochemical findings and managed with cornstarch, carnitine and riboflavin supplements. He did not experience metabolic crises between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia, and generalized weakness associated with acute illnesses and growth spurts. At age 18 years, he developed exercise intolerance and proximal muscle weakness leading to the identification of multiple acyl-CoAdehydrogenase and complex II/III deficiencies in both skeletal muscle and liver. Subsequent molecular characterization of the ETFDH gene revealed novel heterozygous mutations, p.G274X:c.820 G>T (exon 7) and p.P534L: c.1601 C>T (exon 12), the latter within the iron sulfur-cluster and predicted to affect ubiquinone reductase activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept of a structural interaction between ETFDH and other enzyme partners, and suggests that the conformational change upon ETF binding to ETFDH may play a key role in linking ETFDH to II/III super-complex formation.
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影响因子：
6.6
作者：
Klein, Ophir D.;Kostiner, Dana R.;Weisiger, Kara;Moffatt, Ellen;Lindeman, Neal;Goodman, Stephen;Tuchman, Mendel;Packman, Seymour
通讯作者：
Packman, Seymour
影响因子：
4.8
作者：
Henriques, Barbara J.;Rodrigues, Joao V.;Gomes, Claudio M.
通讯作者：
Gomes, Claudio M.
影响因子：
4.2
作者：
Bonham, JR;Guthrie, P;Fairbanks, LD
通讯作者：
Fairbanks, LD
影响因子：
3.8
作者：
Schiff, M;Froissart, R;Vianey-Saban, C
通讯作者：
Vianey-Saban, C
影响因子：
14.5
作者：
Olsen, Rikke K. J.;Olpin, Simon E.;Morris, Andrew A. M.
通讯作者：
Morris, Andrew A. M.