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標題: | 新生兒聽損基因與聽力篩檢於感覺神經性聽損之研究 Audiologic and Molecular Genetic Newborn Screening in Sensorineural Hearing Loss |
作者: | Yu-Hsin Kao 高佑欣 |
指導教授: | 李建南(Chien-Nan Lee) |
關鍵字: | 聽力障礙,感覺神經性聽損,新生兒聽力篩檢,自動化聽性腦幹反應,新生兒聽損基因篩檢, Hearing Impairment,Sensorineural Hearing Loss,Audiologic Newborn Screening,AABR (Automated auditory brainstem response),Molecular Genetic Newborn Screening, |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 聽力障礙是人類最常見的感覺系統缺陷的其中一種。台灣嬰幼兒出生時就罹患輕、中度及重度先天性聽力障礙的發生率約為千分之三,還有個案出生時的聽損程度不嚴重,在成長的過程中,才出現愈來愈嚴重的聽力障礙。由於嬰幼兒時期的聽力下降會影響語文和口頭語言表達能力的發展,因此目前全球對於新生兒聽力障礙早期診斷、早期療育,已達一致的共識。「遺傳因素」佔所有先天性聽力障礙的一半以上,而現行的新生兒聽力篩檢,是使用自動化聽性腦幹反應AABR儀器檢查,對於遺傳因素造成漸進式聽力障礙的新生兒,卻可能無法由AABR篩檢測得。自2009年起,臺大醫院根據國人遺傳性聽損之基因資料庫,針對三個最常見的感覺神經性聽損相關的基因:GJB2 (或稱Cx26 )基因、SLC26A4 (或稱PDS )基因及粒線體 12S rRNA 基因,進行「新生兒聽損基因篩檢」。
本研究針對自2010年6月至2012年6月於臺大醫院出生之新生兒,將「新生兒聽損基因篩檢」與現行的「新生兒聽力篩檢」的結果進行資料收集和結果分析,並針對「新生兒聽損基因篩檢」異常的個案做病歷回溯。結果發現這段期間接受「新生兒聽力篩檢」人數為5980名新生兒,結果需要轉介的人數有122人,佔2.04%。這5980名新生兒中,同時接受「新生兒聽損基因篩檢」人數為2961人,篩檢結果正常Wild Type為2346人佔79.23%,帶因者為580人佔19.59%,其餘的35人為基因異常須轉介追蹤的個案,佔1.18%,包括GJB2 c.109G>A Homozygote 28人,GJB2 c.109G>A / c.235delC Compound Heterozygote 6人,及 Mitochondrial m.1555 A>G Homoplasmy 1人。帶有不同聽損基因型的35名新生兒,分析其出生時接受「新生兒聽力篩檢」AABR的結果發現:只有6人不通過須轉介。換句話說,有29名新生兒潛在聽力有問題,卻無法在現行的新生兒聽力篩檢被檢查出來,而兩項篩檢重複檢出的個案只有0.2%,因此可知兩項篩檢可以檢出不同的聽損族群,可以相輔相成,無法互相取代,且基因型為Mitochondrial m.1555 A>G的個案,不可使用氨基糖苷類的抗生素,提早確認篩檢結果,對其有效地預防早期聽損的發生及惡化幫助很大。針對「新生兒聽損基因篩檢」結果需要轉介的新生兒,進行病歷查閱發現回診共17人,回診率(指回診耳鼻喉科接受聽力檢查追蹤)為48.57%,其中出生時AABR通過11人中,有2人於一歲時聽力35db為輕度聽力障礙,另有2人OAE均為需refer持續追蹤,其餘7人目前聽力正常持續追蹤。其餘6名個案出生時AABR須轉介的,有1人一歲時確診為聽力障礙個案,目前已進行早療,有1人一歲時35db為輕度聽力障礙,有4人一歲的OAE(otoacoustic emission)均為需refer需持續追蹤。 依照「新生兒聽損基因篩檢」的結果,能確認病因、預防疾病惡化,且發生率比多數現行「先天性新生兒篩檢」的人口還多,因此期望未來能將此項篩檢,合併列入新生兒篩檢計畫內,讓父母能提早了解此項篩檢的重要性,另外針對家族內有母系遺傳性聽損的病患或所有尚未有語言發展的新生兒,在選擇氨基糖苷類的抗生素使用前,建議先進行基因檢測,排除帶有Mitochondrial m.1555 A>G,再行使用此類藥物。所有被檢出的個案,建議後續結合「新生兒聽力篩檢」作業系統,及衛生署國民健康局所提供的「新生兒健檢補助」,管理與追蹤需轉介的個案,發揮此篩檢的最大效益。 Hearing impairment is one of the most common sensory system disorders in humans. 3 in 1000 infants in Taiwan are born with mild, moderate or severe hearing impairment. Some of the cases did not have obvious hearing impairment but hearing functions were gradually deteriorated as they grow up. Hearing impairment during infancy will affect the development of language and communication skills. Thus, there is current consensus of early diagnosis and treatment for neonatal hearing impairment. Current neonatal hearing screening uses automated auditory brainstem response (AABR) on neonates born within one month. However, AABR is not capable of screening hearing impairment due to genetic factors, which accounts about more than half of congenital hearing loss. According to the national genetic database of genetic related hearing disorder, GJB2 (also known as Cx26) gene, SLC26A4 (also known as PDS) gene and the mitochondrial 12S rRNA gene are the three most common genes related to sensorineural hearing loss. Since 2009, National Taiwan University Hospital (NTUH) started using these 3 genes for 'newborn genetic screening for hearing loss.' This retrospective study analyzed and compared results of both AABR and newborn genetic screening for hearing loss. It included the newborn in NTUH from June 2010 to June 2012 who undergone AABR or newborn genetic screening for hearing loss. 5980 newborn had AABR done, with 122 (2.04%) newborn referring for follow up. In the 5980 patients, 2961 patients had newborn genetic screening for hearing loss. 79.23% had wild type, 580 were genetic carriers, and 35 (1.18%) patients were referred for follow up. The patients referred for follow up included 28 newborn with GJB2 c.109G> A Homozygote, 6 newborn with GJB2 c.109G>A/c.235delC Compound Heterozygote, 1 newborn with Mitochondrial m.1555 A>G Homoplasmy. Only 6 newborn who were referred for follow-up had abnormal AABR results. The other 29 had potential hearing impairment in the future but could not be identified during the AABR test. Since only 0.2% of the 2961 newborn had positive results of both tests, the two tests are complementary and cannot substitute each other. The case with mutation at the Mitochondrial m.1555 A>G gene could not use the aminoglycoside group antibiotics and would benefit from early detection and preventing worsening of hearing. Analysis of the medical records showed the follow-up rate (follow-up at the ENT clinic for hearing tests) of newborn with positive results of 'newborn genetic screening for hearing loss' was 48.57%. A total of 17 people were back to the clinic for follow-up. Among the 6 newborn with positive AABR results, one was diagnosed with hearing impairment and undergone early treatment, one was diagnosed with mild hearing impairment (35db) at 1-year old, four had OAE diagnosed at 1-year old, all of them required long-term follow-up. In the remaining 11 newborn, two had mild hearing impairment (35db) at 1-year old, two were required to refer for OAE follow-up, and the remaining seven currently have normal hearing and are still being followed up. The results of the 'newborn genetic screening of hearing loss' may give us more information of the etiology of hearing impairment and help us prevent disease progression. The incidence of hearing impairment is higher than the current population screened by the 'congenital newborn screening' project, so we plan to integrate the test into the newborn screening program to let the parents learn the importance of this screening test. In newborn with family history of maternal inherited hearing loss or those without language development, it is recommended to conduct genetic testing to rule out carriers of Mitochondrial m.1555 A> G before choosing to use aminoglycoside antibiotics. All cases with positive results are recommended to join the newborn hearing screening project, and with the support from 'newborn health check subsidy' provided by the Department of Health of the Bureau of Health Promotion, we can manage and track referrals required, making the maximum efficiency of the screening. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61814 |
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