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Office of Rare Diseases

Second Workshop on Trimethylaminuria
March 15 – 16, 2002 • Bethesda, Maryland


Agenda  Participants  Proceedings from journal

Agenda

 
Workshop Co-Chairs: John Cashman, Ph.D. and Eileen Treacy, M.D., FRCPC, FCCMG.
Friday, March 15
 
  Day 1 Workshop's Scientific Sessions
8:00 a.m. Welcome! and Introductions
Henrietta Hyatt-Knorr, M.A.
Acting Director, Office of Rare Diseases (ORD), NIH
8:10 a.m. Workshop Overview/Opening Remarks
Workshop Co-Chairs - Dr. John Cashman and Dr. Eileen Treacy
8:30 a.m. Trimethylaminuria -
Diagnosis, Biochemical and Molecular Aspects
  Overview of The Condition of Trimethylaminuria
Dr. Steve Mitchell (London, UK)
9:05 a.m. The British Experience of Trimethylaminuria:
1984 - 2000

Dr. Robert Smith (London, UK)
9:35 a.m. Patients with Trimethylaminuria: Genotype and Phenotype
Dr. George Preti and Dr. Steven Fakharzadeh (Philadelphia, USA)
10:35 a.m. Laboratory Detection of Trimethylaminuria (TMAU):
Progress & Problems

Susan S. Tjoa and Dr. Paul V. Fennessey (Colorado, USA)
11:05 a.m. Trimethylaminuria and Variation of the FM03 Gene, Genotype - Phenotype Correlations
Dr. Eileen Treacy (Dublin, Ireland)
  Stable Isotope Dilution Measurement of Urinary Trimethylamine and Trimethylamine N-Oxide by Fast Atom Bombardment Mass Spectrometry
Dr. Orval A. Mamer (Montreal, Canada)
11:50 a.m. Discussions and Questions from the Audience
Panel of all speakers from the morning sessions
  Potential Role of Human Brain FMOs in Neurodegeneration
Dr. Jun Zhang (San Diego, USA)
2:45 p.m. Molecular Mechanisms Regulating Tissue-Selective and Developmental-Specific Human Hepatic FMO1 and FMO3 Expression
Dr. Ronald Hines (Wisconsin, USA)
3:15 p.m. Polymorphic Expression Among Ethnic Groups of Pulmonary Flavin-Containing Monooxygenase Isoform 2
Dr. David E. Williams (Oregon, USA)
4:00 p.m. Modulation of Flavin Monooxygenases in Fish Species by Osmotic Pressure and the Potential Relationship to Hypertension
Dr. Daniel Schlenk (California, USA)
4:30 p.m. Discussions and Questions from the Audience
Panel of all speakers from the afternoon sessions
5:00 p.m. ORD and the Rare Diseases Community
(Office of Rare Diseases-NIH)

Henrietta Hyatt-Knorr M.A. (Maryland, USA)

Question and Answers
Saturday, March 16
 
  Day 2 Patient-Oriented Sessions, Panels and Discussions
8:00 a.m. Trimethylaminuria: Patient Perspectives
8:00 a.m. The Right to Earn A Living Free of Harassment and Discrimination
Patti DeWid (California, USA)
8:10 a.m. International Patient Panel
  Patients on this inclusive and diversified panel will briefly tell their stories and/or speak out on issues.
Moderator: Patti DeWid
Panelists: Thelma McNeil (Virginia, USA)
David Ellis (New York, USA)
Kay Wade (Texas, USA)
Lauren Fouhy (New Zealand)
Gisele (The Netherlands)
Brief Report on 2001 Questionnaire on Trimethylaminuria
  Question and Answer session
8:40 a.m. Trimethylaminuria in South Africa; a Student's Experience and Perspective
Schaun Korff
  Question and Answer Session
8:55 a.m. Psychosocial Aspects of the Trimethylaminuria Experience
Dr. Rick Rader (Tennessee, USA)
  Question and Answer Session
9:40 a.m. What are the Treatment Approaches to a Rare Genetic Disorder such as Trimethylaminuria?
Dr. Eileen Treacy (Dublin, Ireland)
10:00 a.m. TMAU: How do I get tested, what do the Results Mean, and where do I go from here if I have it?
Debby Lambert (Montreal, Canada)
Question and Answer Session
11:00 a.m. Nutrition Support for Individuals with Trimethylaminuria: A Practical and Theoretical Approach
Dr. Steven Yannicelli (Ohio, USA)
11:45 a.m. Trimethylaminuria: Good Nutrition Despite Restriction
Kathryn Camp (Washington, USA)
12:15 p.m. Question and Answer Session
12:30 p.m. A Stable Isotope Dilution Assay for Plasma Choline by Direct Infusion Electrospray Mass Spectrometry
Dr. Orval A. Mamer (Montreal, Canada)
  Question and Answer Session
1:15 p.m. Special Program Designed for People with Trimethylaminuria and/or their Families
1:15 p.m Perspectives on: How to Get Medical Treatment from your Doctor
Debby Lambert (Montreal, Canada)
1:30 p.m. Life with a Rare Disease and Resources Available to Help now
Patricia Foote (Virginia, USA)
Author: How Are You? Manage Your Own Medical Journey
Debby Lambert (Montreal, Canada)
  Question and Answer Session
2:00 p.m. Food flavoring and Trimethylamine
Dr. Tim Adams (Washington, USA)
2:20 p.m. Approaches to Treatment: A Panel Discussion
Dr. George Preti (Philadelphia, USA)
Panelists: Dr. Eileen Treacy, Dr. Steve Mitchell, Dr. Robert Smith and Dr. John Cashman.
2:55 p.m. Discussion of Alternative Therapies
Question and Answer Session
3:30 p.m. Prospects for Research: A Panel Discussion
Moderator: Dr. John Cashman (San Diego, USA)
6 Panelists
4:05 p.m. General Question and Answer Session

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Speakers

Timothy B. Adams, Ph.D.
Scientific Consultant
Flavor and Extract Manufacturer's Association

Kathryn Camp, M.S., R.D., C.S.P.
Assistant Professor of Pediatrics/Pediatric Nutritionist
Unformed Services University of the Health Sciences
Walter Reed Army Medical Center

John Cashman, Ph.D.
Director, Human BioMolecular Research Institute; San Diego, CA.

Steven Fakharzadeh, M.D., Ph.D.
Assistant Professor, Dermatology, University of Pennsylvania

Paul Fennessey, Ph.D.
Professor, Department of Pediatrics & Pharmacology;
University of Colorado Health Sciences Center

Patricia Foote, M.A.
Speaker and Author

Ronald N. Hines, Ph.D.
Professor and Co-Director, Birth Defects Research Center
Department of Pediatrics; Medical College of Wisconsin and Children's Hospital of Wisconsin

Henrietta Hyatt-Knorr, M.A.
Acting Director, Office of Rare Diseases(ORD)
Office of the Director(OD), National Institutes of Health (NIH)

Debby Lambert, M.Sc., C.G.C.
Genetics Counselor
McGill University Health Center, Montreal Children's Hospital
Biochemical Genetics Unit

Orval A. Mamer, Ph.D.
Director, The Mass Spectrometry Unit, and
Professor of Medicine, McGill University

Steve Mitchell, Ph.D., D.Sc.
Molecular Toxicology, Division of Biomedical Sciences
Imperial College School of Medicine
London, England

George Preti, Ph.D.
Member, Monell Chemical Senses Center
Adjunct Professor, Department of Dermatology - School of Medicine,
University of Pennsylvania

Rick Rader, M.D.
Director, Morton J. Kent Habilitation Center and
Editor-In-Chief, Exceptional Parent Magazine

Daniel Schlenk, Ph.D.
Professor, Aquatic Ecotoxicology
Department of Environmental Sciences; University of California, Riverside

Robert L. Smith, D.Sc., Ph.D.
Retired, Professor and Senior Research Fellow
Molecular Toxicology, Division of Biomedical Sciences
Imperial College School of Medicine
London

Susan (Sioe San) Tjoa, M.Sc.
Research Associate, University of Colorado Health Sciences Center
Department of Pediatrics and Clinical Mass Spectometry

Eileen Treacy, M.D., FRCPC, FCCMG.
Consultant Metabolic Pediatrician/Clinical Geneticist
The National Centre for Inherited Metabolic Diseases, The Children’s Hospital.
Director of Adult Metabolic Services and Co-Director of the Unit.
Dublin, Ireland

David E. Williams, Ph.D.
Professor of Environmental and Molecular Toxicology
Linus Pauling Institute, Oregon State University

Steven Yannicelli, Ph.D., R.D., L.D.
Research Scientist/Metabolic Diseases
Ross Products Division/Abbott Laboratories

Jun Zhang, Ph.D.
Staff Scientist
Human BioMolecular Research Institute, San Diego

Featuring special panels and sessions including

Patient Perspectives Panel: Patti DeWid, Thelma McNeil, David Ellis, and Kay Wade - USA; Lauren Fouhy - New Zealand

Special session with Schaun Korff, South Africa.

The Workshop Planning Committee

Dr. J.R. Cashman; California, USA (Chair)
Dr. Eileen Treacy; Dublin, Ireland (Chair)
Mary Demory; Maryland, USA. (Coordinator)
Sandy Gordon; New York, USA. (Coordinator)
Henrietta Hyatt-Knorr; Maryland, USA
Debby Lambert; Montreal, Canada

Trimethylaminuria Support Group meeting coordinators, panelists and volunteers:  Helen Butler, Felicia Cox, Patti DeWid, David Ellis, Sandy Gordon, Thelma McNeil, Laurie Montes, Yvonne Southerland.

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Summary

The second Workshop on Trimethylaminuria (TMAU) was held on March 15 and 16, 2002 at the National Institutes of Health Campus in Bethesda, Maryland.

The goals of the workshop included: providing quality information, a review of scientific and general data, and a networking forum for individuals with Trimethylaminuria, physicians, research scientists, genetic counselors and other professionals who currently work in and/or support the TMAU community. We accomplished our goals and were able to:

  • Build on the achievements of the first Workshop on Trimethylaminuria (March 1999).

  • Provide access to all individuals with TMAU coming together for the first time to meet each other, knowledgeable participants, and supporters; and increase general knowledge of the trimethylaminuria condition.

  • Provide a forum for participants to facilitate the sharing of their latest findings with peers and colleagues, networking, development of new collaborative initiatives, and consensus building.

  • Discuss strategies to stimulate research: build support for ongoing research efforts; increase general media awareness of TMAU, especially in the medical and scientific community; and develop funding to further ongoing investigations and start new research projects leading to (at least) enhanced treatment solutions that will improve the quality of life and emotional health of individuals with TMAU and their families, and eventually a medical cure.

The presentations by 18 speakers, 4 guest speakers, and 5 panelists covered the following topics:

  1. Definition of trimethylaminuria and review of the general history of the disorder

  2. Synopsis of the remarkable progress in the biochemical, genetic, and clinical basis for understanding the trimethylaminuria disorder

  3. Classification of the disorder into six groups
    • primary genetic form
    • acquired form
    • childhood forms
    • transient form associated with menstruation
    • precursor overload
    • disease states

  4. The flavin-containing monooxygenase (FMO) system, primarily form 3 (responsible for detoxification and deodorization of trimethylamine)

  5. The possible contribution of FMO3 variants in hypertension and other diseases

  6. The disabling and limiting characteristics of TMAU

  7. Biochemical aspects of TMAU

  8. Outline of recent analytical approaches to quantify urinary trimethylamine, trimethylamine N-oxide, and plasma choline

  9. Description of investigators' findings based on data collected at testing centers from individuals testing for TMAU

  10. (Demographic, symptomatic, historical) data collected in 2001 from questionnaires completed by self-reporting individuals with TMAU in support groups

  11. Treatment strategies, including data on nutritional support, dietary sources of trimethylamine, vitamin supplementation, probiotics and drug treatment

  12. Psychosocial considerations and understanding its impact on the lives of individuals with TMAU and their families

  13. The Trimethylaminuria experience in South Africa

  14. Patient Panel highlighting personal experiences and challenges faced by individuals with trimethylaminuria and their families as a direct result of widespread ignorance regarding the condition, strong negative public reactions to incomprehensible and pronounced body odors, inadequate access to medical care support, and health care disparities

  15. Practical and helpful systems that are useful to enhancing patient self-care including knowledge of

    • the purpose and uses of genetic counseling
    • practical symptomatic solutions such as the oral hygiene cleansing practices
    • a comprehensive approach to efficiently managing one's own medical care journey
    • developing and/or maintaining a positive attitude and self image
    • good advice regarding finding credible sources of information on the internet

  16. Increasing targeted awareness of TMAU and bringing this life-disrupting condition to the attention of the media, medical community, investigators pursing parallel areas of research, and more investigators at academic institutions, etc.

Trimethylaminuria: Good Nutrition Despite Restriction
Kathryn Camp
Walter Reed Army Medical Center; Washington, DC, USA

Molecular Basis of Human Trimethylaminuria
John R. Cashman and Jun Zhang
Human BioMolecular Research Institute; San Diego, California, USA

Laboratory Detection of Trimethylaminuria (TMAU)
Progress & Problems

Susan S. Tjoa and Paul V. Fennessey
University of Colorado Health Sciences Center; Denver, Colorado, USA

Stable Isotope Dilution Measurement of Urinary Trimethylamine and Trimethylamine N-Oxide by Fast Atom Bombardment Mass Spectrometry
A Stable Isotope Dilution Assay for Plasma Choline by Direct Infusion Electrospray Mass Spectrometry

Orval A. Mamer, McGill University
McGill University; Montreal, Quebec, Canada

Overview of The Condition of Trimethylaminuria
Steve Mitchell
Biological Chemistry, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, England.

Individuals with Trimethylaminuria: Phenotype and Genotype
George Preti, Ph.D.1,2. and Steven Fakharzadeh, M.D, Ph.D.1,2
1Monell Chemical Senses Center, Phila., PA 19104 and 2Dept. of Dermatology,
School of Medicine, University of Pennsylvania, USA

Psychosocial Aspects of The Trimethylaminuria Experience
Rick Rader, MD
Morton J. Kent Habilitation Center; Chattanooga, Tennessee, USA
and Exceptional Parent Magazine

Modulation of Flavin Monooxygenases in Fish Species by Osmotic Pressure and the Potential Relationship to Hypertension.
Daniel Schlenk
University of California; Riverside, California, USA

Factors Underlying the Causation of Trimethylaminuria
Robert L. Smith
Biological Chemistry, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, England.

Trimethylaminuria and Variation of the FMO3 Gene, Genotype-Phenotype Correlations
E.P. Treacy
The National Centre for Inherited Metabolic Diseases, The Children's Hospital; Dublin, Ireland

Polymorphic Expression Among Ethnic Groups of Pulmonary Flavin-Containing Monooxygenase Isoform 2
David E. Williams
Linus Pauling Institute, Oregon State University; Corvalis, Oregon, USA

Nutrition Support for Individuals with Trimethylaminuria: A Practical and Theoretical Approach
Steven Yannicelli
Pharmavite Corporation; Northridge, California, USA

Potential Role of Human Brain FMOs in Neurodegeneration
Jun Zhang; Quyen Tran, John R. Cashman
Human BioMolecular Research Institute, San Diego, California, U.S.A

The Right to Earn A Living Free of Harassment and Discrimination
A Patient’s Perspective (and an account of a current, ongoing litigation)

Patti DeWid
Costa Mesa, California, USA

Life with a Rare Disease
Patricia Foote
Medical Journeys; Alexandria, Virginia, USA

Trimethylaminuria in South Africa
Schaun Korff
University of Potchefstroom; North West, South Africa

TMAU: How do I get tested, what do the results mean, and where do I go from here if I have it?
Perspectives on “How to get medical treatment from your doctor”

Deborah M. Lambert
McGill University Health Center, Montreal Children's Hospital; Montreal, Quebec, CANADA

Internet Web Sites - the Good, the Bad & (yes) the Ugly
By Carolyn Willard, AMLS AHIP
Reference Librarian, The National Library of Medicine, The National Institutes of Health

Achievements

1. Media Publications. Following are publications directly resulting from the workshop.

Biochemical and Clinical Aspects of the Human Flavin-Containing Monooxygenase, Form 3 (FMO3) Related to Trimethylaminuria, a collaborative review work (by 13 of the speakers from the meeting) accepted for publication in Drug Metabolism Reviews. Anticipated publication date is First Quarter 2003.

Living With Trimethylaminuria, a collaborative article by Eileen Treacy, M.D., a patient family, and the Trimethylaminuria Foundation has been accepted for publication in Exceptional Parent Magazine. Publication date is March 2003.

We anticipate additional publications from other individual participants as well and, as they unfold, will feature links to those websites. These will stimulate a new wave of collaborative efforts in the TMAU community.

Research into the nature of malodors had received considerable attention in the media (during the first quarter of 2002). An article focusing on malodor research at the Monell Chemical Senses Center in Philadelphia was published in Chemical and Engineering News in January of 2002; the Trimethylaminuria disorder was highlighted in one section in which researcher, George Preti, Ph.D., was interviewed. That article created a buzz about body odors for much of 2002. A reporter from Popular Science magazine attended the March workshop as a result of that media exposure.

2. The Diet Guide for Individuals with Trimethylaminuria - a Choline Restricted Diet booklet compiled by Dr. Steven Yannicelli and Ms. Kathryn Camp for this meeting. A low-choline diet has been shown to reduce the malodor symptoms and bring varying levels of relief to individuals with TMAU. This informative food guide helps to reduce both the stress of managing the disorder and the malodor symptoms, and is a very useful tool.

3. A recipe book has been prepared as an additional resource guide for eating a healthy, balanced, low-choline diet, compiled by Marilyn Hutchison (November 2002).

4. Support Connections
A major achievement of the Second Workshop on Trimethylaminuria has been the positive emotional impact on individual attendees and an increased level of awareness for all participants.

Small steps have had a large impact and many individuals with TMAU have reported realizing many personal accomplishments resulting from participation in the workshop, including:

  • a better understanding of the mechanisms and genetics of TMAU, which aids in the medical doctor/patient decision-making process;
  • better understanding of the need for testing and diagnosis, and the testing process; and access to available testing and treatment options;
  • formulation of a comprehensive approach to managing TMAU;
  • choosing to generally increase the level of our individual participation in the TMAU community, and build on peer support and positive modeling to effect personal care changes;
  • a plan to collectively identify and discuss our future needs in the community.

Trimethylaminuria is indeed a disease with no cure and much more meaning work needs to be done to build on current achievements. Areas which are lacking include: further research; human and financial resources; stronger cooperation amongst investigators, and cooperation between investigators and medical care providers; widespread medical awareness of the condition; respect and tolerance for individuals with trimethylaminuria; effective and reasonable accommodation programs in the workplace and schools; and a genuine understanding of the devastating impact of TMAU (emotional, physical and financial) on the lives of individuals suffering with TMAU and their families.

Roadmap of Action Items for the Future

We must encourage the ongoing national debate regarding the need to value all humans and, purposely, those with disabilities, handicaps and rare disorders such as TMAU, and not discard the needs of the few because of the wants of the majority. Encourage corporate involvement through participation in funding research and (employee) support initiatives. Individuals with TMAU and the TMAU community must actively participate in and contribute to such public discussions. Every productive citizen increases the wealth and well being of the city, state, nation and world.

The ongoing development of the TMAU community infrastructure is essential to ensuring that there is a source of quality information, a support base for individuals with TMAU, and a resource channel for our partners. We endeavor to gather and increase the resources required to achieve the scientific research objectives and implement support programs. Current development solutions include:

  1. Website designed to provide: general information on Trimethylaminuria and malodor related issues; and listservs and email communications connections to allow participants to get connected to current issues and events.

  2. Networking and Resource Development -- Employ the goals of the Trimethylaminuria Foundation's Medical and Scientific Advisory Board and work together to: increase targeted general, medical and scientific awareness of TMAU; provide practical and additional resources to individuals with TMAU; and secure research funding for research priorities.

    • Define current consensus positions and identify and clarify issues requiring further discussion, examination and definition.

    • Development of research funding for studies with the primary goal focused on patient care, including:
      • Investigate and examine current methodologies used to test for TMAU; and expand range of testing to include analysis for dimethylglycinuria in the differential diagnosis of metabolic body odor.
      • Develop wider research focus on Trimethylaminuria to advance research initiatives that may provide good scientific and clinical information that will be used to provide new data and insights, and establish enhanced treatment strategies.
      • Find improved drug treatment(s) with the potential to satisfy the unmet medical needs of those individuals with severe and untreated symptoms and those who are now without therapeutic alternatives (especially children with TMAU).
      • Further investigate the psychosocial impact resulting from societal response to individuals with TMAU and the associated stigma.

    • Stimulate greater collaborations among research scientists through expanded opportunities to participate in parallel research projects, disease task forces, etc., and share resources of national research centers such as common research tools, databases, and research sharing programs.

    • Attract new investigators to this area of research. Develop chair endowments at academic institutions, fellowships, and other programs. Connect with and participate in related studies at national research centers.

    • Develop more patient/research scientist-teams for media exposure in Awareness Campaign.

    • Information dissemination -- Get information and the words trimethylaminuria, body odor, malodor, FOS, etc. into medical texts, general reference books, hospital databases, etc.

  3. Expand current report on recommended dietary restrictions (Yannicelli and Camp's report, March 2002); annually update and publish a comprehensive CHOLINE FOOD LISTING summary. Utilize new info from the FDA and other available research databases; collaborate on project with other nutritionists and dieticians (including current TMAU care providers); include new sections on nutritional needs for Children with TMAU and Other Special Needs.

  4. Publishing of new TMAU-related works, including new patient-centered educational Information Resource documents; a Physician's Guide brochure; etc.

  5. Encourage and instigate various studies including those required to gather more information from wider population of individuals with TMAU; test and examine findings, track progress of participants over long-term period; collect, examine and analyze new range of phenotype and genotype specimen and data to develop information database, and follow with prospective study to develop further evidence for better treatment options.

Workshop co-chairs, advisors, co-coordinators:
John Cashman, Sandy Gordon, Deborah Lambert, George Preti, Eileen Treacy, Mary Demory, Henrietta Hyatt-Knorr

You may address Correspondence to:

Trimethylaminuria Foundation
P O Box 3361
Grand Central Station
New York NY 10163-3361
Tel: 212-678-2506
Email: Trimeth411@aol.com

Office of Rare Diseases (ORD);
Office of the Director, National Institutes of Health
Email: ord@od.nih.gov
www.rarediseases.info.nih.gov/index.html

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Last Reviewed: September 16, 2003
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