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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李妮鍾(Ni-Chung Lee) | |
| dc.contributor.author | Tsung-Chien Chen | en |
| dc.contributor.author | 陳宗謙 | zh_TW |
| dc.date.accessioned | 2021-06-16T04:18:49Z | - |
| dc.date.available | 2014-10-09 | |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-19 | |
| dc.identifier.citation | 1. Liang, W.C. and I. Nishino, Lipid storage myopathy. Curr Neurol Neurosci Rep, 2011. 11(1): p. 97-103.
2. Wen, B., et al., Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. J Neurol Neurosurg Psychiatry, 2010. 81(2): p. 231-6. 3. Lan, M.Y., et al., High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-onset lipid storage myopathy. Clin Genet, 2010. 78(6): p. 565-9. 4. Schiff, M., et al., Electron transfer flavoprotein deficiency: functional and molecular aspects. Mol Genet Metab, 2006. 88(2): p. 153-8. 5. Er, T.K., et al., High resolution melting analysis facilitates mutation screening of ETFDH gene: applications in riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Clin Chim Acta, 2010. 411(9-10): p. 690-9. 6. Er, T.K., et al., Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif. BMC structural biology, 2011. 11: p. 43. 7. Wang, Z.Q., et al., Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A. J Mol Med (Berl), 2011. 89(6): p. 569-76. 8. Yotsumoto, Y., et al., Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2. Mol Genet Metab, 2008. 94(1): p. 61-7. 9. Rinaldo, P., T.M. Cowan, and D. Matern, Acylcarnitine profile analysis. Genet Med, 2008. 10(2): p. 151-6. 10. Gregersen, N., Riboflavin-responsive defects of beta-oxidation. J Inherit Metab Dis, 1985. 8 Suppl 1: p. 65-9. 11. Gregersen, N., et al., Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency. Assessment of 3 years of riboflavin treatment. Acta Paediatr Scand, 1986. 75(4): p. 676-81. 12. Prasad, M. and S. Hussain, Glutaric Aciduria Type II Presenting as Myopathy and Rhabdomyolysis in a Teenager. J Child Neurol, 2014. 13. Angle, B. and B.K. Burton, Risk of sudden death and acute life-threatening events in patients with glutaric acidemia type II. Mol Genet Metab, 2008. 93(1): p. 36-9. 14. Gordon, N., Glutaric aciduria types I and II. Brain Dev, 2006. 28(3): p. 136-40. 15. Liang, W.C., et al., ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Neuromuscul Disord, 2009. 19(3): p. 212-6. 16. Xi, J., et al., Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis, 2014. 37(3): p. 399-404. 17. Law, L.K., et al., Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Clin Chim Acta, 2009. 404(2): p. 95-9. 18. Wasant, P., et al., Glutaric aciduria type 2, late onset type in Thai siblings with myopathy. Pediatr Neurol, 2010. 43(4): p. 279-82. 19. Olsen, R.K., et al., ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain, 2007. 130(Pt 8): p. 2045-54. 20. Kaminsky, P., et al., Subacute myopathy in a mature patient due to multiple acyl-coenzyme A dehydrogenase deficiency. Muscle Nerve, 2011. 43(3): p. 444-6. 21. Sahai, I., et al., Newborn Screening for Glutaric Aciduria-II: The New England Experience. JIMD Rep, 2013. 22. Boles, R.G., et al., Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr, 1998. 132(6): p. 924-33. 23. Rashed, M.S., et al., Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile. Clin Chem, 1995. 41(8 Pt 1): p. 1109-14. 24. Chien, Y.H., et al., Fatty Acid oxidation disorders in a chinese population in taiwan. JIMD Rep, 2013. 11: p. 165-72. 25. Vockley, J., Glutaric aciduria type 2 and newborn screening: commentary. Mol Genet Metab, 2008. 93(1): p. 5-6. 26. Sahai, I., et al., Newborn Screening for Glutaric Aciduria-II: The New England Experience. JIMD Rep, 2014. 13: p. 1-14. 27. Hall, P.L., et al., Postanalytical tools improve performance of newborn screening by tandem mass spectrometry. Genetics in medicine : official journal of the American College of Medical Genetics, 2014. 28. Woodward, J., Bi-allelic SNP genotyping using the TaqMan(R) assay. Methods Mol Biol, 2014. 1145: p. 67-74. 29. Catarzi, S., et al., Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico predictions, and molecular studies. ScientificWorldJournal, 2013. 2013: p. 625824. 30. Wood, J.C., et al., Diagnosis of very long chain acyl-dehydrogenase deficiency from an infant's newborn screening card. Pediatrics, 2001. 108(1): p. E19. 31. McHugh, D., et al., Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet Med, 2011. 13(3): p. 230-54. 32. Poplawski, N.K., et al., Multiple acyl-coenzyme A dehydrogenase deficiency: diagnosis by acyl-carnitine analysis of a 12-year-old newborn screening card. The Journal of pediatrics, 1999. 134(6): p. 764-6. 33. Browning, M.F., et al., Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects. Journal of inherited metabolic disease, 2005. 28(4): p. 545-50. 34. Chiong, M.A., et al., Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Molecular genetics and metabolism, 2007. 92(1-2): p. 109-14. 35. Knoppers, B.M., et al., Whole-genome sequencing in newborn screening programs. Sci Transl Med, 2014. 6(229): p. 229cm2. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55710 | - |
| dc.description.abstract | 背景
現行新生兒篩檢可以利用串聯質譜儀分析，對於戊二酸血症第二型（Glutaric aciduia type II; GA II）又稱為多發性醯基輔酶A去氫酶缺乏症(multiple acyl-coenzyme A dehydrogenase deficiency；MADD)的患者提供早期診斷的機會，但目前選用串聯質譜儀分析血片中的數種乙醯肉鹼(acylcarnitines)濃度是否異常的準確度仍有待改進。 方法 我們回顧性的分析了296,929件新生兒篩檢血片串聯質譜議分析的結果，利用檢驗後分析工具Tool runner – GA-II分析，大於35分者依分數高低分為高度懷疑或是可能為GA II (細分為高風險及低風險組)，再採用Taqman single nucleotide polymorphisms (SNP) Genotyping Assays分析這些樣本中是否帶有台灣地區GA II的基因突變熱點（A84T與R99G)，並以定序方式加以確認。 結果 共有1,103件(0.4%)樣本的分數符合為高度懷疑或是可能為GA II。在高度懷疑個案中，三個為其他脂肪酸代謝異常患者，另外有2名個案確認為GA II患者。在高風險及低風險組中的1,091個個案中共發現14個有A84T的突變(13名雜合子及1名同合子)，A84T在此研究中的帶因率為1.35%，與先前文獻的帶因率相似。A84T同合子的乙醯肉鹼數值並無明顯異常的指標。 結論 以Tool runner – GA-II可以有效篩選脂肪酸代謝異常包括GA II的患者，但是無法檢出帶有A84T的新生兒。如何增進此類患者的偵測率仍有待進一步研究。 | zh_TW |
| dc.description.abstract | Background
Glutaric acidemia type II (GA II), also known as multiple acyl-coenzyme A dehydrogenase deficiency (MADD), is an autosomal recessive disease caused by electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) defects. Currently, the diagnosis of GA II in newborn screening dependent on tandem mass spectrometry analysis but the sensitivity is unknown. Method We retrospectively analyzed 296,929 acylcarnitines data of newborn screening results using Tool Runner-GA-II. Score higher than 35 were defined as likely or probably (high risk and low risk) to be GA II. We then analyzed if they have A84T and R99G of ETFDH gene by Taqman single nucleotide polymorphisms (SNP) Genotyping Assays. All positive cases were confirmed by direct sequencing. Result Totally 1,103 cases (0.4%) were selected as likely or probably GA II. Six cases were in the likely group included three cases of other fatty acid oxidation defects, and 2 cases of GA II. Fourteen of the 1,091 analyzed cases in the probably groups had A84T mutation (13 heterozygous, 1 homozygous). A84T allele frequency in this study is 1.35%, similar to other studies. The one with A84T homozygous mutation showed normal acylcarnitines at first screening. Conclusion Tool Runner – GA-II can identifies fatty acid oxidation defects including some GA II patients. However, it can’t be a solely tool to detect Taiwan newborns with A84T mutation. Further study is necessary to improve the detection rate. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T04:18:49Z (GMT). No. of bitstreams: 1 ntu-103-P01448003-1.pdf: 3071290 bytes, checksum: 4702a9745787a5ef2f357085e3127db9 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 中文摘要 i
英文摘要 ii 圖目錄 v 表目錄 vi 附錄 vii 第一章 研究背景與動機 1 1.1 脂質儲積型肌肉病變 1 1.2 戊二酸血症第二型 1 1.3 戊二酸血症第二型在台灣 2 1.4 新生兒篩檢對於戊二酸血症第二型的重要性 3 1.5 戊二酸血症第二型新生兒篩檢現行方法的盲點 3 1.6 研究動機 4 第二章 材料與方法 5 2.1 研究大綱 5 2.2 檢體 5 2.3 分析方法 5 2.4 分析原理 5 2.4.1 Tool runner - GA-II 5 2.4.2 即時聚合酶鏈反應 6 2.4.3 聚合酶鏈反應 6 2.4.4 凝膠純化 7 2.5 實驗品質與管制 7 2.5.1檢體保存品質 7 2.52對照實驗與盲樣試驗 7 2.6 統計分析 7 第三章 結果 8 3.1 檢體分布 8 3.2 突變熱點分析 8 3.3 突變確認 9 3.4 檢體acylcarnitine數據分析 10 第四章 討論 12 第五章 結論 15 第六章 參考文獻 40 | |
| dc.language.iso | zh-TW | |
| dc.subject | 戍二酸血症第二型 | zh_TW |
| dc.subject | 多發性醯基輔?A去氫?缺乏症 | zh_TW |
| dc.subject | 新生兒篩檢 | zh_TW |
| dc.subject | 脂質儲積型肌肉病變 | zh_TW |
| dc.subject | Glutaric adiduria type II (GA II) | en |
| dc.subject | newborn screening | en |
| dc.subject | Lipid myopathy | en |
| dc.subject | multiple acyl-CoA dehydrogenase deficiency(MADD) | en |
| dc.title | 新生兒篩檢在診斷核黃素反應型多發性醯基輔酶A去氫酶缺乏症（MADD）之可行性研究 | zh_TW |
| dc.title | Diagnosis of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) by newborn screening: a feasibility study | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 簡穎秀(Yin-Hsiu Chien),胡務亮(Wuh-Liang Hwu) | |
| dc.subject.keyword | 多發性醯基輔?A去氫?缺乏症,戍二酸血症第二型,新生兒篩檢,脂質儲積型肌肉病變, | zh_TW |
| dc.subject.keyword | multiple acyl-CoA dehydrogenase deficiency(MADD),Glutaric adiduria type II (GA II),newborn screening,Lipid myopathy, | en |
| dc.relation.page | 42 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-20 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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