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2017/12/10.
概述

囊性纤维化(cystic fibrosis, CF)是一种比较常见的遗传性疾病,它是由人类第7对常染色体突变所引起的。在人类的体细胞中(除外男性的精子细胞,女性的卵细胞、卵母细胞)都含有46条即23对染色体。其中一半遗传自母亲,另一半遗传自父亲。这些染色体上的基因通过表达而控制体内蛋白质的合成,从而决定生物体的表型。在正常情况下,囊性纤维跨膜蛋白(cystic fibrosis transmembrane regulator, CFTR)是由位于第7对染色体上的一个基因调控合成的,这种染色体的突变(在DNA平上的缺失)导致CFTR的合成缺失或缺陷,从而引起了CF。现已有1000多种CF的突变形式得到了确认,其中的一些形式是比较常见的。

由于CF是一种隐性遗传病,所以患病者必须是第7对染色体CFTR基因突变的纯合子,即从父母双方各遗传到一条不正常的染色体基因。而只有一条染色体上CFTR基因突变,另一条染色体正常的个体称为携带者。携带者既无临床症状亦不患病,但他们可以把致病基因遗传给下一代。因此,患病者的亲生父母双方都至少有一条致病基因,即他们必须是携带者或患病者。北欧的高加索人和德系犹太人有较高的CF患病率,大约每20-25人中有1人是携带者。

CF患者由于CFTR蛋白的合成及功能的缺陷,导致上皮细胞中水和电解质的跨膜转运障碍,从而产生浓厚粘稠的黏液,结果堵塞支气管继发肺部感染,亦可堵塞胰腺和肝脏导管,引起蛋白消化障碍。大多数男性患者还可表现为不育,原因是从睾丸向外运送精子的输精管发育不良或缺失。大多数患者早年出现呼吸道和胰腺的症状,即使患者之间的基因突变方式相同,其表现的临床症状严重程度也是因人而异的。

囊性纤维化病是美国最常见的一种隐性遗传疾病。据统计大概有3万美国人患有该病,每年新增病例约1000人。目前尚无明确的预防和治愈该疾病的方法,只能以对症治疗为主要手段。但针对此病治疗方法的研究近10年来取得了较大的进展,目前已可使一些患者延长生命,改善了生活质量。

 

骼和胸部的X线检查,上消化道和小肠的检查以及肺功能检查。

Related Pages


On This Site
Tests: CF Gene Mutation, Sweat Chloride, Immunoreactive Trypsinogen (IRT), Stool trypsin and chymotrypsin
Conditions: Lung diseases
Screening: Pregnancy & Prenatal Testing, Cystic Fibrosis
Articles: Universe of Genetic Testing

Elsewhere On The Web
Cystic Fibrosis Foundation
Your Genes, Your Health: Cystic Fibrosis
Boomer Esiason Foundation: Fighting Cystic Fibrosis
Howard Hughes Medical Institute: Discovering the Gene for Cystic Fibrosis
ACOG: Cystic Fibrosis Carrier Testing, The Decision is Yours

Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

(July 2008) National Heart, Lung and Blood Institute. Diseases and Conditions: What is Cystic Fibrosis? Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/cf/cf_what.html through http://www.nhlbi.nih.gov. Accessed January 2009.

Cystic Fibrosis Foundation. Treatments: Lung Transplantation. Available online at http://www.cff.org/treatments/LungTransplantation/ through http://www.cff.org. Accessed January 2009.

Liou TG, Adler FR, Cox DR, Cahill BC. Lung transplantation and survival in children with cystic fibrosis. N Engl J Med. 2007 Nov 22; 357(21):2 143-52. Available online through http://www.ncbi.nlm.nih.gov/pubmed. Accessed January 2009.

Cystic Fibrosis Foundation. About Cystic Fibrosis. Available online at http://www.cff.org/AboutCF/ through http://www.cff.org. Accessed January 2009.

American Lung Association. What is Cystic Fibrosis? Available online at http://www.lungusa.org/site/apps/nlnet/content3.aspx?c=dvLUK9O0E&b=4294229&ct=5290039 through http://www.lungusa.org. Accessed January 2009.

Denise I. Quigley, PhD, FACMG. Co-Director Cytogenetics/Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.

Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

NIDDK (July 1997). Cystic Fibrosis Research Directions. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [NIH Publication No. 97-4200]. Available online at http://www.niddk.nih.gov/health/endo/pubs/cystic/cystic.htm through http://www.niddk.nih.gov.

CFF. Sweat Testing Procedure and Commonly Asked Questions. Cystic Fibrosis Foundation [On-line information]. Available online at http://www.cff.org/publications01.htm through http://www.cff.org.

Tait, J., et. al. (26 March 2001). Cystic Fibrosis. GENEReviews [On-line information]. Available online at http://www.genetests.org/.

Mayo Clinic (2001, February 09). What is Cystic Fibrosis? Mayo Clinic [On-line information]. Available online at http://www.mayoclinic.com/invoke.cfm?objectid=2CEBF76F-D36A-4D15-B937BFF91AB51438 through http://www.mayoclinic.com.

MEDLINEplus (2002, January 2, Updated). Cystic Fibrosis. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000107.htm.

MEDLINEplus (2002, January 2, Updated). Sweat Electrolytes. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003630.htm.

MEDLINEplus (2002, January 2, Updated). Trypsin and chymotrypsin in stool. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003594.htm.

Mountain States Genetics (1999, September, Revised). Cystic Fibrosis (CF). Newborn Screening Practitioner’s Manual [On-line information]. Available online at http://www.mostgene.org/pract/prac26.htm through http://www.mostgene.org.

National Institutes of Health (1995, November). Facts About Cystic Fibrosis. National Heart, Lung, and Blood Institute NIH Publication No. 95-3650 [On-line information]. Available online at http://www.nhlbi.nih.gov/health/public/lung/other/cf.htm through http://www.nhlbi.nih.gov.

Quest Diagnostics NEWS (2002, Winter). What is the Best Test to Screen for Cystic Fibrosis? [On-line serial]. PDF available for download at http://www.questdiagnostics.com/hcp/files/02winter_newsletter.pdf through http://www.questdiagnostics.com.

MEDLINEplus (2002, January 2, Updated). Neonatal cystic fibrosis screening. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003409.htm.

Drkoop (2001). Cystic fibrosis. Medical Encyclopedia [On-line information]. Available online at http://www.drkoop.com/conditions/ency/article/000107.htm through http://www.drkoop.com/conditions/ency/article/000107.htm.

MEDLINEplus (2002, January 2, Updated). Trypsinogen. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003560.htm.

Biomedical Hypertext (1999 May 20, last update). Exocrine Secretions of the Pancreas. Colorado State University [On-line information]. Available online at http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html through http://arbl.cvmbs.colostate.edu.

UPCMD (1998 – 2002). Cystic Fibrosis. University Pathology Consortium, LLC [On-line information]. Available online at http://www.upcmd.com/dot/examples/00218/description.html through http://www.upcmd.com.

Sainato, D. (2002, March). Genetic Testing for CF Going Mainstream? Clinical Laboratory News [Journal], Vol 28.

Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.

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  • 症状和体征

    CF的体征症状包括:

    • 反复咳嗽、久咳咳痰
    • 反复或持续的胸部感染,如支气管炎、肺炎
    • 腹部疼痛或不适
    • 新生儿胎粪性肠梗阻
    • 慢性腹泻、恶臭粪便、脂肪便
    • 体重下降或营养不良
    • 生长发育停滞―患儿虽食欲旺盛,但生长发育仍迟缓
    • 血液中蛋白减少和水肿

    CF可导致体内水电解质失衡。大多数患者汗液中的盐分(氯化钠)可为正常人的5倍。钠和氯的大量丢失可引起心率失常,有时甚至可引起休克。

    CF患者肺中原本起润滑作用的黏液变得浓厚粘稠,为微生物的生长繁殖提供了良好的环境,导致频繁的呼吸道感染。这时必须通过静脉注射、口服和/或吸入抗生素进行治疗。大多CF患者都是因呼吸道感染和肺部并发症而首次发病的。

    胰腺导管被粘稠物堵塞,由于胰酶不能进入肠道消化蛋白质和脂肪,引起吸收障碍。这可导致维生素缺乏和营养不良。口服胰酶和服用脂溶性的维生素A、D、E、K,再搭配低脂高蛋白饮食可以缓解症状。如果胰腺受损严重,一些患者最终可以继发糖尿病

    其它与囊性纤维化病有关的症状包括:

    • 胆道结石
    • 胰腺炎
    • 生长发育迟缓和青春期性发育延迟
    • 杵状指(趾)
    • 慢性肝病胆汁性 肝硬化
    • 直肠脱垂
    • 男性不育(梗阻性精子缺乏)

     

  • 试验

    CF突变基因检测:美国医学遗传学会和美国妇产学会都推荐检测CF最常见的23种突变基因的组合,对一般或特定人群进行CF和CF携带情况的普查(一些实验室可检测30-96种突变基因)。此方法为打算怀孕的或妊娠早期的夫妻双方进行DNA检测,以此确定他们是否有导致CF的突变基因。如果夫妻双方都确定有该病的突变基因,那么遗传学顾问应该向夫妇说明育儿可能患CF的相对危险度。

    汗液氯化物检测:是检测通过特殊途径收集的汗液标本中氯化物的含量。CF的典型症状之一是汗液盐分含量极高。由于CFTR蛋白的改变或缺失,导致氯化物转运受限,因此CF患者的汗液盐分含量约是普通人的5倍。汗液氯化物检测阳性可为诊断该病提供依据,如果条件允许,一般和CF突变基因检测联合应用。一些病例只要根据汗液氯化物检测结果便可做出诊断,但有极少数病例的汗液氯化物含量可能正常。

    胰蛋白酶/胰凝乳蛋白酶检测:是检测粪便中蛋白水解酶的试验。胰腺产生无活性的胰蛋白酶,进入小肠被激活后参与食物蛋白质的消化。正常人该试验结果为阳性。这是一项筛查胰腺分泌功能是否正常的试验。

    免疫反应性胰蛋白酶原(Immunoreactive Trypsinogen, IRT)检测:新生儿胰蛋白酶原的筛查试验,胰蛋白酶原是由胰腺合成并进入肠道的,在肠道活化形成胰蛋白酶,CF患者可产生粘稠的黏液堵塞胰腺导管而阻碍胰蛋白酶原进入肠道。CF患儿血中IRT含量可升高,但该试验的假阳性率较高(由于CF以外的原因和/或一过性升高所影响),因此需要确认试验加以验证。

    鼻电位差(Nasal Potential Difference NPD)检测:离子转运活动,主要是钠离子和氯离子,它们通过呼吸道上皮细胞(覆盖在鼻腔内层的细胞),使鼻腔内产生一个可以测量的跨膜电位差。CF患者的钠和氯离子转运失常,以致产生了与正常人不同的电位差。鼻电压差检测可为诊断CF提供帮助。

    其它检查器官功能、生育能力、肺部感染的试验包括:

    其它非实验室检查还包括骨

  • 预防、早期发现和治疗

    目前,尚无根治CF的方法,只能做到缓解症状和改善患者的生存质量。治疗目标包括积极的去除肺内多余的黏液,防止肺部感染;防止胃肠道消化道堵塞;通过特殊饮食为患者提供充足的营养;一些治疗方法还将身体锻炼和物理疗法与抗生素、抗炎药、气管扩张药等联合使用。

    预防CF的方法目前尚不明确,只能对人群的致病基因携带情况进行筛查,以及加强对CF患病风险的遗传咨询服务。

    在胎儿出生之前,便可通过对羊水绒毛膜进行CF基因突变的检测,诊断胎儿是否患有该病。现在新生儿健康普查项目里已新加入了免疫反应性胰蛋白酶检测和CF基因突变检测。早期诊断可以使患儿的父母通过CF中心接受一定的关于该病的知识和特殊的帮助。早期诊断有助于早期治疗,使患儿的营养发育不良和肺部损伤降到最低的程度。

    一些患者可能需要接受肺移植,但该方法是否能使患者延长生命或提高生存质量,尚不十分明确。

    现针对此病治疗方法的有关研究正在进行,并且在近10年来取得了较大的进步,已经能做到在提高患者的生存质量的前提下延长患者的生命。

     

  • 要提出的问题

    以下是你需要向你的健康顾问提出的问题:

    1. 对我的情况来讲,DNA检测与其它CF筛查试验相比,它的优势是什么?

    2. 我们做CF筛查试验的最佳时间是什么时候?

    3. 我的孩子应该做CF相关的试验吗?

    4. 国家是强制要求还是建议做新生儿CF筛查试验?我需要申请吗?

    5. 我的种族对我患CF的风险有怎样的影响?是否有某种CF的基因突变类型在我的种族特别常见?是否有足够的关于我的种族和家族史与该疾病研究的信息?

    6. 对父母双方都进行该疾病的检查有何利弊?您建议在同一时间进行检查还是不同时间进行试验?

    7. 根据对CF的筛查和实验室检查的结果,我是否应该了解遗传学方面的知识,还是应该和遗传学顾问或医学遗传学家进行交流?

    8. 我家庭里还有哪些成员可能是该病的携带者?了解CF检查的结果对我们有什么好处吗?

来源

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

(July 2008) National Heart, Lung and Blood Institute. Diseases and Conditions: What is Cystic Fibrosis? Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/cf/cf_what.html through http://www.nhlbi.nih.gov. Accessed January 2009.

Cystic Fibrosis Foundation. Treatments: Lung Transplantation. Available online at http://www.cff.org/treatments/LungTransplantation/ through http://www.cff.org. Accessed January 2009.

Liou TG, Adler FR, Cox DR, Cahill BC. Lung transplantation and survival in children with cystic fibrosis. N Engl J Med. 2007 Nov 22; 357(21):2 143-52. Available online through http://www.ncbi.nlm.nih.gov/pubmed. Accessed January 2009.

Cystic Fibrosis Foundation. About Cystic Fibrosis. Available online at http://www.cff.org/AboutCF/ through http://www.cff.org. Accessed January 2009.

American Lung Association. What is Cystic Fibrosis? Available online at http://www.lungusa.org/site/apps/nlnet/content3.aspx?c=dvLUK9O0E&b=4294229&ct=5290039 through http://www.lungusa.org. Accessed January 2009.

Denise I. Quigley, PhD, FACMG. Co-Director Cytogenetics/Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.

Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

NIDDK (July 1997). Cystic Fibrosis Research Directions. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [NIH Publication No. 97-4200]. Available online at http://www.niddk.nih.gov/health/endo/pubs/cystic/cystic.htm through http://www.niddk.nih.gov.

CFF. Sweat Testing Procedure and Commonly Asked Questions. Cystic Fibrosis Foundation [On-line information]. Available online at http://www.cff.org/publications01.htm through http://www.cff.org.

Tait, J., et. al. (26 March 2001). Cystic Fibrosis. GENEReviews [On-line information]. Available online at http://www.genetests.org/.

Mayo Clinic (2001, February 09). What is Cystic Fibrosis? Mayo Clinic [On-line information]. Available online at http://www.mayoclinic.com/invoke.cfm?objectid=2CEBF76F-D36A-4D15-B937BFF91AB51438 through http://www.mayoclinic.com.

MEDLINEplus (2002, January 2, Updated). Cystic Fibrosis. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000107.htm.

MEDLINEplus (2002, January 2, Updated). Sweat Electrolytes. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003630.htm.

MEDLINEplus (2002, January 2, Updated). Trypsin and chymotrypsin in stool. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003594.htm.

Mountain States Genetics (1999, September, Revised). Cystic Fibrosis (CF). Newborn Screening Practitioner’s Manual [On-line information]. Available online at http://www.mostgene.org/pract/prac26.htm through http://www.mostgene.org.

National Institutes of Health (1995, November). Facts About Cystic Fibrosis. National Heart, Lung, and Blood Institute NIH Publication No. 95-3650 [On-line information]. Available online at http://www.nhlbi.nih.gov/health/public/lung/other/cf.htm through http://www.nhlbi.nih.gov.

Quest Diagnostics NEWS (2002, Winter). What is the Best Test to Screen for Cystic Fibrosis? [On-line serial]. PDF available for download at http://www.questdiagnostics.com/hcp/files/02winter_newsletter.pdf through http://www.questdiagnostics.com.

MEDLINEplus (2002, January 2, Updated). Neonatal cystic fibrosis screening. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003409.htm.

Drkoop (2001). Cystic fibrosis. Medical Encyclopedia [On-line information]. Available online at http://www.drkoop.com/conditions/ency/article/000107.htm through http://www.drkoop.com/conditions/ency/article/000107.htm.

MEDLINEplus (2002, January 2, Updated). Trypsinogen. MEDLINEplus Health Information [On-line Information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003560.htm.

Biomedical Hypertext (1999 May 20, last update). Exocrine Secretions of the Pancreas. Colorado State University [On-line information]. Available online at http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html through http://arbl.cvmbs.colostate.edu.

UPCMD (1998 – 2002). Cystic Fibrosis. University Pathology Consortium, LLC [On-line information]. Available online at http://www.upcmd.com/dot/examples/00218/description.html through http://www.upcmd.com.

Sainato, D. (2002, March). Genetic Testing for CF Going Mainstream? Clinical Laboratory News [Journal], Vol 28.

Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR.