ABETALIPOPROTEINEMIA
A
3-in-1
Medical
Reference
A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers TO INTERNET REFERENCES
ABETALIPOPROTEINEMIA A BIBLIOGRAPHY AND DICTIONARY FOR PHYSICIANS, PATIENTS, AND GENOME RESEARCHERS
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Copyright ©2007 by ICON Group International, Inc. Copyright ©2007 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Abetalipoproteinemia: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers/ James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11316-3 1. Abetalipoproteinemia-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on abetalipoproteinemia. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Chaired Professor of Management Science at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Fax: 858-635-9414 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ABETALIPOPROTEINEMIA ......................................................................... 3 Overview........................................................................................................................................ 3 Genetics Home Reference ............................................................................................................... 3 What Is Abetalipoproteinemia?...................................................................................................... 3 How Common Is Abetalipoproteinemia? ....................................................................................... 4 What Genes Are Related to Abetalipoproteinemia?....................................................................... 4 How Do People Inherit Abetalipoproteinemia? ............................................................................. 4 Where Can I Find Additional Information about Abetalipoproteinemia? ..................................... 4 References....................................................................................................................................... 6 What Is the Official Name of the MTTP Gene?............................................................................. 6 What Is the Normal Function of the MTTP Gene? ....................................................................... 7 What Conditions Are Related to the MTTP Gene? ....................................................................... 7 Where Is the MTTP Gene Located? ............................................................................................... 7 References....................................................................................................................................... 8 Federally Funded Research on Abetalipoproteinemia .................................................................... 9 The National Library of Medicine: PubMed ................................................................................ 11 CHAPTER 2. ALTERNATIVE MEDICINE AND ABETALIPOPROTEINEMIA ......................................... 30 Overview...................................................................................................................................... 30 National Center for Complementary and Alternative Medicine.................................................. 30 Additional Web Resources ........................................................................................................... 31 General References ....................................................................................................................... 32 APPENDIX A. HELP ME UNDERSTAND GENETICS ......................................................................... 34 Overview...................................................................................................................................... 34 The Basics: Genes and How They Work....................................................................................... 34 Genetic Mutations and Health..................................................................................................... 45 Inheriting Genetic Conditions ..................................................................................................... 51 Genetic Consultation ................................................................................................................... 59 Genetic Testing ............................................................................................................................ 61 Gene Therapy ............................................................................................................................... 67 The Human Genome Project and Genomic Research................................................................... 70 APPENDIX B. PHYSICIAN RESOURCES ............................................................................................. 73 Overview...................................................................................................................................... 73 NIH Guidelines............................................................................................................................ 73 NIH Databases............................................................................................................................. 74 Other Commercial Databases....................................................................................................... 77 APPENDIX C. PATIENT RESOURCES ................................................................................................ 78 Overview...................................................................................................................................... 78 Patient Guideline Sources............................................................................................................ 78 Finding Associations.................................................................................................................... 80 Resources for Patients and Families............................................................................................. 81 ONLINE GLOSSARIES.................................................................................................................. 82 Online Dictionary Directories ..................................................................................................... 84 ABETALIPOPROTEINEMIA DICTIONARY ............................................................................ 85 INDEX .............................................................................................................................................. 113
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FORWARD In March 2001, the National Institutes of Health issued the following warning: “The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.”1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with abetalipoproteinemia is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about abetalipoproteinemia, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to abetalipoproteinemia, from the essentials to the most advanced areas of research. Special attention has been paid to present the genetic basis and pattern of inheritance of abetalipoproteinemia. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on abetalipoproteinemia. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to abetalipoproteinemia, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. We hope these resources will prove useful to the widest possible audience seeking information on abetalipoproteinemia. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/.
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CHAPTER 1. STUDIES ON ABETALIPOPROTEINEMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on abetalipoproteinemia. For those interested in basic information about abetalipoproteinemia, we begin with a condition summary published by the National Library of Medicine.
Genetics Home Reference Genetics Home Reference (GHR) is the National Library of Medicine’s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on abetalipoproteinemia that describes the major features of the condition, provides information about the condition’s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to abetalipoproteinemia is provided. 2 The Genetics Home Reference has recently published the following summary for abetalipoproteinemia:
What Is Abetalipoproteinemia?3 Abetalipoproteinemia is an inherited disorder that affects the absorption of dietary fats, cholesterol, and certain vitamins. People affected by this disorder are not able to make certain lipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides. These lipoproteins, referred to as beta-lipoproteins, include low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), and chylomicrons. A lack of beta-lipoproteins prevents absorption through the digestive tract of dietary fats and fat-soluble vitamins such as vitamins E, A, and sometimes K. Sufficient
2 3
This section has been adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/.
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/condition=abetalipoproteinemia.
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Abetalipoproteinemia
levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues, particularly nerve cells and tissues in the eye. The signs and symptoms of abetalipoproteinemia appear in the first few months of life. They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal star-shaped red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea). Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia), and progressive degeneration of the lightsensitive layer (retina) at the back of the eye that can progress to near-blindness. Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which can lead to the nerve problems associated with this disorder.
How Common Is Abetalipoproteinemia? Abetalipoproteinemia is a rare disorder with approximately 100 cases described worldwide.
What Genes Are Related to Abetalipoproteinemia? Mutations in the abetalipoproteinemia.
MTTP
(http://ghr.nlm.nih.gov/gene=mttp)
gene
cause
The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein, which is essential for creating beta-lipoproteins. These lipoproteins are necessary for the absorption of fats, cholesterol, and fat-soluble vitamins from the diet and the efficient transport of these substances in the bloodstream. Most of the mutations in this gene lead to the production of an abnormally short microsomal triglyceride transfer protein, which prevents the normal creation of beta-lipoproteins in the body.
How Do People Inherit Abetalipoproteinemia? This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
Where Can I Find Additional Information about Abetalipoproteinemia? You may find the following resources about abetalipoproteinemia helpful. These materials are written for the general public.
Studies
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NIH Publications - National Institutes of Health •
National Heart, Lung, and Blood Institute: Abetalipoproteinemia, patient recruitment for lipid disorders: http://patientrecruitment.nhlbi.nih.gov/LipidDisorders.aspx
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Office of Dietary Supplements: http://ods.od.nih.gov/Health_Information/Information_About_Individual_Dietary_Su pplements.aspx MedlinePlus - Health Information
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Encyclopedia: Bassen-Kornzweig syndrome: http://www.nlm.nih.gov/medlineplus/ency/article/001666.htm
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Encyclopedia: Malabsorption: http://www.nlm.nih.gov/medlineplus/ency/article/000299.htm
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Encyclopedia: Stools - floating: http://www.nlm.nih.gov/medlineplus/ency/article/003128.htm
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Health Topic: Blood and Blood Disorders: http://www.nlm.nih.gov/medlineplus/bloodandblooddisorders.html
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Health Topic: Neurologic Diseases: http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Educational Resources - Information Pages
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Lipoproteins Transport Cholesterol and Triacylglycerols Throughout the Organism (Biochemistry, Fifth Edition 2002): http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.3628#3634
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Madisons Foundation: http://www.madisonsfoundation.org/content/3/1/display.asp?did=605
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Orphanet: http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=14
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The Merck Manual of Medical Information, Second Home Edition, Online Version: http://www.merck.com/mmhe/sec12/ch157/ch157c.html
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The University of Kansas Hospital: Vitamin A: http://www.kumed.com/xmlindex.cfm?chunkiid=14043
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The University of Kansas Hospital: Vitamin E: http://www.kumed.com/xmlindex.cfm?chunkiid=14070
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The University of Kansas Hospital: Vitamin K: http://www.kumed.com/xmlindex.cfm?chunkiid=21883 Patient Support - for Patients and Families
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http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Abetalipoprotei nemia
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Abetalipoproteinemia
Professional Resources You may also be interested in these resources, which are designed for healthcare professionals and researchers. •
ClinicalTrials.gov - Linking patients to medical research: http://clinicaltrials.gov/search/condition=%22abetalipoproteinemia%22+OR+%22Hyp olipoproteinemia%22?recruiting=false
•
PubMed - Recent literature: http://ghr.nlm.nih.gov/condition=abetalipoproteinemia/show/PubMed;jsessionid=179 6EC438EE487F9B9CFA8C592A550CE
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Online Books - Medical and science texts: http://books.mcgrawhill.com/getommbid.php?isbn=0071459960&template=ommbid&c=115
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OMIM - Genetic disorder catalog: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=200100
References These sources were used to develop the Genetics Home Reference condition summary on abetalipoproteinemia. •
Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, Wetterau JR. The role of the microsomal triglygeride transfer protein in abetalipoproteinemia. Annu Rev Nutr. 2000;20:663-97. Review. PubMed citation
•
Hooper AJ, van Bockxmeer FM, Burnett JR. Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism. Crit Rev Clin Lab Sci. 2005;42(5-6):515-45. PubMed citation
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Hussain MM, Iqbal J, Anwar K, Rava P, Dai K. Microsomal triglyceride transfer protein: a multifunctional protein. Front Biosci. 2003 May 1;8:s500-6. Review. PubMed citation
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Hussain MM. A proposed model for the assembly of chylomicrons. Atherosclerosis. 2000 Jan;148(1):1-15. Review. PubMed citation
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Shelness GS, Ledford AS. Evolution and mechanism of apolipoprotein B-containing lipoprotein assembly. Curr Opin Lipidol. 2005 Jun;16(3):325-32. Review. PubMed citation
A summary of the gene related to abetalipoproteinemia is provided below:
What Is the Official Name of the MTTP Gene?4 The official name of this gene is “microsomal triglyceride transfer protein.”
4
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=mttp;jsessionid=1796EC438EE487F9B9CFA8C592A550CE.
Studies
7
MTTP is the gene's official symbol. The MTTP gene is also known by other names, listed below.
What Is the Normal Function of the MTTP Gene? The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein. The microsomal triglyceride transfer protein helps produce betalipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides. These beta-lipoproteins contain apolipoprotein B and are critical for the creation of molecules called chylomicrons, which are formed when dietary fats and cholesterol are absorbed through the intestines. The absorption of dietary fat via chylomicrons is also necessary for the absorption of certain fat-soluble vitamins, especially vitamins E, A, and sometimes K. Other beta-lipoproteins containing apolipoprotein B, particularly low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), are created by microsomal triglyceride transfer protein in the liver. The lipoproteins transport fats, cholesterol, and fat-soluble vitamins throughout the body by way of the bloodstream. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues, particularly nerve cells and tissues in the eye.
What Conditions Are Related to the MTTP Gene? Abetalipoproteinemia - Caused by Mutations in the MTTP Gene More than 15 mutations that cause abetalipoproteinemia have been identified in the MTTP gene. Almost all of these mutations result in the production of an abnormally short microsomal triglyceride transfer protein. This shortened protein is unable to produce betalipoproteins, resulting in a severe deficiency of chylomicrons, low-density lipoproteins, and very low-density lipoproteins. The absence of these lipoproteins prevents dietary fats and fat-soluble vitamins from being absorbed and carried to the rest of the body, leading to the signs and symptoms of abetalipoproteinemia.
Where Is the MTTP Gene Located? Cytogenetic Location: 4q24 Molecular Location on chromosome 4: base pairs 100,715,003 to 100,763,648
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Abetalipoproteinemia
The MTTP gene is located on the long (q) arm of chromosome 4 at position 24. More precisely, the MTTP gene is located from base pair 100,715,003 to base pair 100,763,648 on chromosome 4.
References These sources were used to develop the Genetics Home Reference gene summary on the MTTP gene. •
Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, Wetterau JR. The role of the microsomal triglygeride transfer protein in abetalipoproteinemia. Annu Rev Nutr. 2000;20:663-97. Review. PubMed citation
•
Entrez Gene
•
Hooper AJ, van Bockxmeer FM, Burnett JR. Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism. Crit Rev Clin Lab Sci. 2005;42(5-6):515-45. PubMed citation
•
Hussain MM, Iqbal J, Anwar K, Rava P, Dai K. Microsomal triglyceride transfer protein: a multifunctional protein. Front Biosci. 2003 May 1;8:s500-6. Review. PubMed citation
•
OMIM
•
Shelness GS, Ledford AS. Evolution and mechanism of apolipoprotein B-containing lipoprotein assembly. Curr Opin Lipidol. 2005 Jun;16(3):325-32. Review. PubMed citation
•
Swift LL, Kakkad B, Boone C, Jovanovska A, Jerome WG, Mohler PJ, Ong DE. Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett. 2005 Jun 6;579(14):3183-9. PubMed citation
•
Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M, Schmitz J, Gay G, Rader DJ, Gregg RE. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. 1992 Nov 6;258(5084):999-1001. PubMed citation
•
Wetterau JR, Aggerbeck LP, Laplaud PM, McLean LR. Structural properties of the microsomal triglyceride-transfer protein complex. Biochemistry. 1991 May 7;30(18):440612. PubMed citation
Studies
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Federally Funded Research on Abetalipoproteinemia The U.S. Government supports a variety of research studies relating to abetalipoproteinemia. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.5 CRISP (Computerized Retrieval of Information on Scientific Projects) CRISP is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to abetalipoproteinemia. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore abetalipoproteinemia. The following is typical of the type of information found when searching the CRISP database for abetalipoproteinemia: •
Project Title: APOB AND APOA-I KINETICS IN THE APOB-67 MUTATION Principal Investigator & Institution: Welty, Francine K.; Beth Israel Deaconess Medical Center 330 Brookline Avenue, Br 264 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 15-AUG-1997; Project End 30-JUN-2007 Summary: (provided by applicant): Hypobetalipoproteinemia (HBLP) is characterized by low levels of apoB (
