F ANCONI ANEMIA : A Handbook for Families and Their Physicians

FANCONI
ANEMIA
A Handbook for Families
and Their Physicians
Third Edition, 2000
Lynn and Dave Frohnmayer

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FANCONI ANEMIA: A Handbook for Families
and Their Physicians
by Lynn and Dave Frohnmayer
Editing, design, layout, and cover design: Joyce Owen
copyright© 2000
First Printing: April 1993
Second Edition: March 1995
Third Edition: March 2000
ISBN: 0-615-11292-7
Material from this book may be reprinted with the
permission of the authors or publisher. Additional
copies are available from the publisher:
Fanconi Anemia Research Fund, Inc.
1801 Willamette Street, Suite 200
Eugene, Oregon 97401
phone:
541-687-4658 or 800-828-4891 (US only)
fax:
541-687-0548
e-mail:
info@fanconi.org
website: http://fanconi.org
Special thanks to Joyce Owen for devoting countless
personal hours to the editing, design and layout of three
editions of this Handbook. Thanks to Mary Ellen Eiler
for expert assistance with proofreading.

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iii
Acknowledgments
The authors are fully responsible for the contents of this
Handbook, but we are deeply grateful to the following
experts who reviewed all or portions of the manuscript
for the First Edition.
Blanche P. Alter, MD
Formerly, Children’s Hospital,
University of Texas Medical Branch
Galveston, Texas
Arleen D. Auerbach, PhD
The Rockefeller University
New York, New York
Grover C. Bagby, Jr., MD
Oregon Health Sciences University
Portland, Oregon
John Hansen, MD
University of Washington and
Fred Hutchinson Cancer Research Center
Seattle, Washington
Joyce L. Owen, PhD
Director Emeritus
Fanconi Anemia Research Fund, Inc.
Eugene, Oregon
Nasrollah T. Shahidi, MD
University of Wisconsin Medical School
Madison, Wisconsin

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The Fanconi Anemia Research Fund, Inc. was founded in 1989 to
provide support to FA families and to raise money for scientific
research. The Fund publishes a newsletter twice a year, sponsors an
annual family meeting, and provides telephone, e-mail, and letter
support to FA families. To aid research into FA, the Fund gives
grants to scientists and sponsors an annual scientific symposium.
Staff
Joachim Schulz, Executive Director
Leslie Roy, Family Support Coordinator
Esther A. Lombardi, Family Services Assistant
Board of Directors
Mary Ellen Eiler, President
David Frohnmayer, JD, Vice President
Barry Rubenstein, JD, Secretary
Vicki Anton-Athens, DPM
Ruby Brockett
Deane Marchbein, MD
Peter von Hippel, PhD
Mike Vangel
Joyce Owen, PhD, Director Emeritus
Advisor to the Board
Lynn Frohnmayer, MSW
Scientific Advisory Board
Grover Bagby, Jr., MD, Chair
Manuel Buchwald, PhD, OC
Richard Gelinas, PhD
Eva Guinan, MD
Hans Joenje, PhD
Christopher Mathew, PhD
Stephen Meyn, PhD
Maria Pallavicini, PhD
Leona Samson, PhD
Kevin Shannon, MD

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Table of Contents
Introduction ............................................................. 1
Chapter One: Definition, Characteristics and
Diagnosis of Fanconi Anemia ............................ 3
What is FA? .................................................................. 3
Is FA the Same as Fanconi Syndrome? ........................ 4
How is FA Related to Other Types of Aplastic Anemia? ..... 4
How is FA Diagnosed? ................................................. 5
1. Chromosome breakage and other tests ............... 5
2. Existence of birth defects ................................... 7
3. Later problems that may affect FA patients ....... 9
4. Appearance of aplastic anemia ........................ 10
5. Myelodysplasia or leukemia ............................ 10
6. Diagnosis of an affected sibling ....................... 10
How is Aplastic Anemia Discovered in FA? .............. 10
Bone Marrow Failure.................................................. 11
What Do We Learn from an FA Patient's Blood Counts? ... 14
When Does Aplastic Anemia Occur in FA? ............... 16
What Other Medical Tests Should the FA Patient
Undergo? What Reports Should We Collect? .......... 16
Abnormal Clones ........................................................ 17
What is the Prognosis for an FA Patient? ................... 18
Could an FA Patient Ever Become Pregnant
or Father a Child? ................................................. 18
Chapter Two: Treatments for Fanconi Anemia .....20
Bone marrow transplantation for FA patients ............. 20
1. Matched sibling donors .................................... 22
2. Umbilical cord transplants ............................... 23
3. Alternate donor transplants .............................. 23

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vi
Fanconi Anemia: A Handbook for Families
Drug therapy for FA patients ...................................... 25
Hematopoietic growth factors and FA ........................ 26
FA Genes and the Potential for Gene Therapy ........... 28
How are genes related to chromosomes
and the human cell? .............................................. 28
Do we know why FA genes are defective? ........... 28
What is the status of gene therapy for FA? ........... 29
A Special Note on Solid Tumor Cancers .................... 30
Chapter Three: Continuing Scientific Study of
Fanconi Anemia ................................................ 31
How Can I Help Hasten Long-term Scientific
Understanding of FA? ........................................... 31
International Fanconi Anemia Registry (IFAR) ......... 32
FA Sample Repository at Dana-Farber Cancer Institute
and Children's Hospital, Boston ........................... 32
FA Cell Repository at Oregon Health
Sciences University ................................................ 33
International Collaborative Study on FA .................... 33
Chapter Four: Coping With Fanconi Anemia ........35
What are Common Reactions to the
Diagnosis of FA? .................................................. 35
What Should the FA Child be Told About
the FA Condition and Treatment? ......................... 36
What About the Reactions of Siblings or
Other Family Members? ....................................... 37
What Should the Extended Family be Told? .............. 37
Where Else Can I Go for Emotional
or Other Support? ................................................. 38
What Else Can Help in Coping With
This Diagnosis? .................................................... 38

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Table of Contents
vii
Appendices
A: Medical Review Checklist for FA Families
Ellis Neufeld MD, PhD ........................................ 40
B: Reactions of Families on the Receiving End
Lynn and Dave Frohnmayer ................................. 45
C: The Physician's Role: A Mother's Perspective
Lynn Frohnmayer, MSW ...................................... 49
D: Toxic Chemicals to Avoid
Joyce L. Owen, PhD ............................................. 55
E: Cells, Chromosomes, and Genes
.............................................................................. 57
F: Autosomal Recessive Inheritance
Sandra Grilliot, MS .............................................. 59
G: Prenatal Diagnosis of FA
Susan Olson, PhD ................................................. 63
H: Mutation Analysis of Cloned FA Genes
Arleen Auerbach, PhD ......................................... 68
I:
Tissue Typing and Donor Selection:
The HLA System
John A. Hansen, MD ............................................ 74
J: Matched Sibling Donor Transplant
Richard Harris, MD .............................................. 84
K: Alternate Donor Transplant
Margaret MacMillan, MD and John Wagner, MD ... 95
L: Gene Therapy: Risks and Potential
Chris Walsh, MD, PhD ....................................... 114
M: Mosaicism in FA
Hans Joenje, PhD ................................................ 120
N: The Gastrointestinal Tract and FA
Sarah Jane Schwarzenberg, MD ......................... 123
O: Dental Care for FA Patients
Elise Bolski, DDS ............................................... 128

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viii
Fanconi Anemia: A Handbook for Families
P: Controlling Bleeding with Amicar®
Wayne Rackoff, MD, Richard Harris, MD,
Jeff Lipton, MD, and Blanche Alter, MD ........... 130
Q: Gynecology and Pregnancy
Blanche P. Alter, MD .......................................... 131
R: Malignancies in FA Patients
Blanche P. Alter, MD .......................................... 133
S: Squamous Cell Cancers of the Head and Neck
Frank Ondrey, MD .............................................. 136
T: FA Cell Repository
at Oregon Health Sciences University
Markus Grompe, MD ......................................... 140
U: New FA Center in Boston
Alan D'Andrea, MD ............................................ 145
V: Lead FA Families and Organizations
Throughout the World
............................................................................ 150
W: Support Resources for FA Families
............................................................................ 154
X: Additional Reading
Johnson M. Liu, MD .......................................... 162
Y: Glossary
............................................................................ 187
About the Authors
............................................................................ 197

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1
Introduction
This Handbook gives basic information, in plain
language, about understanding and coping with a
serious disorder known as Fanconi anemia, or FA.
The initial FA diagnosis is always a shock. Once it has
been absorbed, families of FA patients and their
friends—and even physicians—may search for months
for trustworthy information. Families also react
emotionally to the grim prognosis. They feel
understandable anger, denial, grief, unfounded guilt
or withdrawal. As parents of FA children, we personally
know each of these reactions.
This Handbook answers common questions in simple
terms. We include more technical information in a
number of appendices. We are deeply grateful for the
experience of researchers, treating physicians and
other families in our worldwide support group.
Many medical words—especially those with Latin and
Greek origins—confuse families. Complicated words
may be a real barrier to your understanding of FA and
your discussions with your doctors. Our text defines
many confusing terms. We also include a glossary of
medical and scientific terms you may see or hear (Appen-
dix Y). Words in bold type are defined in this glossary.
This Handbook is the result of many hours of research
and consultation, and years of experience. It is written
for lay people by lay people. We are not doctors, but we
follow progress in FA-related science on a daily basis.
All medical information included here should always be
reviewed with your own treating physician. If you have

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Fanconi Anemia: A Handbook for Families
questions relating to treatment or prognosis, please raise
these issues with your doctor or with an appropriate
specialist. The Fanconi Anemia Research Fund recently
published Fanconi Anemia: Standards for Clinical
Care, a handbook for treating physicians. Copies are
available from the FARF office.
Do not be surprised if world-famous experts disagree.
You may read or hear conflicting medical advice. That
problem is common even with well-known illnesses.
But FA is a rare orphan disease. The biological
processes that threaten FA patients are poorly
understood. Doctors should welcome your questions.
Many might encourage you to get a second opinion.
We know how serious this disorder is. FA has claimed
too many lives. We make no exaggerated promises, and
we create no false hopes of instant cure. But progress in
medical science relating to FA has been very rapid and
encouraging in the last decade. Even as we write, new
developments in genetic research and improved
therapies may make our information out of date.
We welcome that progress in every way.
This Handbook is dedicated to the memory of special
children and young adults—claimed by FA so unfairly
before reaching their full potential. We also dedicate this
manual to the physicians and researchers who are work-
ing to understand, treat, and cure this hateful affliction.
We hope that this Handbook helps you in your own
family struggle. Join us, if you can, in active efforts to
seek effective treatments, to obtain funding for medical
research, and to find a cure.
Dave and Lynn Frohnmayer
March, 2000

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Document Outline

• Front Matter
• Table of Contents
• Introduction
• Chapter 1: Definition of FA
  • What is FA?
  • Is FA the Same as Fanconi Syndrome?
  • How is FA Related to Other Types of Aplastic Anemia?
  • How is FA Diagnosed?
    • 1. Chromosome breakage
    • 2. Birth defects
    • 3. Later problems
    • 4. Aplastic anemia
    • 5. Myelodysplasia or leukemia
    • 6. Affected sibling
  • How is Aplastic Anemia Discovered?
  • Bone Marrow Failure
  • Blood Counts
  • When Does Aplastic Anemia Occur?
  • Other Medical Tests
  • Abnormal Clones
  • Prognosis
  • Fertility
• Chapter 2: Treatments
  • Bone Marrow Transplant
    • 1. Matched sib
    • 2. Cord blood
    • 3. Alternate donor
  • Drug Therapy
  • Growth Factors
  • Gene Therapy
  • Cancer
• Chapter 3: Continuing Study
  • How Can I Help?
    • 1. IFAR Registry
    • 2. Dana-Farber Repository
    • 3. OHSU Repository
    • 4. International Study
• Chapter 4: Coping
  • Reactions to Diagnosis
  • What Should FA Child be Told?
  • Reactions of Sibs
  • Extended Family
  • Emotional Support
  • Help in Coping
• Appendices
• A: Checklist: Neufeld
• B: Reaction of Families: Frohnmayer
• C: Physician's Role: Frohnmayer
• D: Toxic Chemicals: Owen
• E: Cells, Chromosomes, Genes
• F: Recessive Inheritance: Grilliot
• G: Prenatal Diagnosis: Olson
• H: Mutation Analysis: Auerbach
• I: Tissue Typing: Hansen
• J: Matched Sib Transplant: Harris
• K: Alternate Donor Transplant: MacMillan & Wagner
• L: Gene Therapy: Walsh
• M: Mosaicism: Joenje
• N: GI Tract: Schwartzenberg
• O: Dental Care: Bolski
• P: Control Bleeding
• Q: Gynecology: Alter
• R: Malignancies: Alter
• S: Head&Neck Cancers: Ondrey
• T: Cell Repository at OHSU: Grompe
• U: FA Center in Boston: D'Andrea
• V: Lead Families Worldwide
• W: Support Resources
• X: Additional Reading: Liu
• Y: Glossary
• About the Authors

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