Rare Disease Impact Report: Insights from patients and the medical community

Abstract

This report was commissioned by Shire Human Genetic Therapies and developed in collaboration with an external advisory board.

Full text

Rare Disease Impact Report:
Insights from patients and the medical community
April 2013
This report was commissioned by Shire Human Genetic Therapies and developed in collaboration with an external advisory board.

Table of Contents
Foreword ............................................................................................1
Acknowledgments ..............................................................................2
Introduction ........................................................................................3
Methodology ......................................................................................4
Combined Summary of Key Findings ................................................6
Patient/Caregiver Findings .................................................................9
Physician Findings ...........................................................................17
Payor Findings ..................................................................................21
Appendix .........................................................................................24

“This new report from Shire highlights and confi rms the issues
faced by patients affected by rare diseases. The inclusion and
comparison of clinicians’, payors’ and patients’ experiences
demonstrate the importance of working together, as a
community, to tackle the issues faced by patients. It also
highlights the importance of working with the international
rare disease community in order to share best practices and
information for all those affected.”
Alastair Kent, Director, Genetic Alliance UK
At Shire Human Genetic Therapies
(HGT), patients are at the heart
of everything we do. We are
dedicated to researching,
developing, and marketing novel
products that enhance the quality
of life of patients suffering from
rare diseases. However, despite
the progress that has been
made over the past few
decades to help improve
the quality of life and
care for patients with
rare diseases, there is
still an urgent need to
better understand the
unique challenges
of rare diseases so
that appropriate
measures can
be taken to
address any
gaps in care.
This is why Shire HGT, in
collaboration with an expert
global panel of patient advocates,
physicians, and policy experts in the
rare disease  eld, conducted survey
research in the United States (US) and
United Kingdom (UK) to determine the
health, psycho-social, and economic
impact of rare diseases among
patient and medical communities.
Key  ndings published in this Rare
Disease Impact Report identify and
quantify the impact of rare diseases
based on survey responses from
a multi-stakeholder audience of
patients/caregivers, physicians,
payors, and thought leaders. We hope
this report will serve as a sustainable
tool that will drive a dialogue about
the future of research, patient care,
and access so as to improve the lives
of people living with rare diseases and
the families that care for them.
“This Impact Report brings to light the specifi c barriers
to quality care that exist for patients with rare diseases,
particularly the challenges in getting an accurate diagnosis,
adequate information and ongoing care.”
Nicole Boice, Founder and CEO, Global Genes | RARE Project
Foreword
Flemming Ørnskov, MD, Chief Executive Offi cer Designate, Shire
1

We would like to thank our external advisory board who contributed signi cantly to the development
of this Report: Nicole Boice, Founder and CEO, Global Genes | RARE Project; Dr. Priya S. Kishnani,
Division Chief, Medical Genetics, Duke University Medical Center; Tomas Philipson, Daniel Levin
Professor of Public Policy Studies, The University of Chicago; Alastair Kent, Director, Genetic Alliance
UK; Dr. Christian J. Hendriksz, Clinical Lead, Adult Inherited Metabolic Disorders, Salford Royal NHS
Foundation Trust; and Mike Drummond, Professor of Health Economics, University of York.
We would also like to thank Joel Middleton, Assistant Professor of Applied Statistics, New York
University, who contributed to the survey questionnaire design and survey analysis.
Acknowledgments
2

Globally, some 7,000 rare diseases have been
identi ed.1 Compared to widespread conditions
that strike hundreds of millions of people, rare
diseases can lack similar levels of interest
amongst the general public and medical/
research communities. Most of these individual
diseases receive little attention because they
affect only thousands – or sometimes only
hundreds – of patients worldwide.2
Yet looking at rare diseases as a collective
entity, we are able to realize their expansive
impact. Collectively, there are approximately
30 million people living with a rare disease in
the US and another 3.5 million in the UK.3,4
Around the globe, the rare disease community
is estimated to include 350 million people.5 And
rare diseases touch more than just the patient.
These conditions also impact families, friends,
caregivers, physicians, payors, and society
as a whole.
There is an urgent need to understand the state
of rare diseases and the current gaps in care
and support. To address this need, in January
2013, Shire HGT conducted online surveys
over a four-week period among US/UK rare
disease patients and their caregivers, physicians
treating patients with rare diseases, payors
who handle reimbursements for healthcare
plans and government/institutions, and thought
leaders in the rare disease space. Surveys were
 elded through market research agency ORC
International and also distributed by advocacy
group partners Global Genes and the Genetic
Alliance UK.
Based on survey responses from a multi-
stakeholder audience sample, the overarching
concerns centered on several key themes:
There are a lack of resources and information •
to address these less common illnesses
The economic impact of diagnosing and •
managing rare diseases is signi cant
Rare diseases take a major emotional toll on •
patients/caregivers
Patients, physicians, and payors alike cited
the extensive time it takes to diagnose a rare
disease along with the uncertainty of treating
many of them as the two key drivers of both
cost and emotional stress. The entire care
journey for many patients is characterized by
misdiagnosis, con icting medical opinions and
stress.
Introduction:
Uncovering the Impact of Rare Diseases
3
Greater collaboration among physicians and 1.
access to specialists with expertise in rare
diseases. Patient and physician responses
point to the need for increased awareness,
more educational programs, and additional
networking opportunities or platforms
connecting general practitioners and patients
with appropriate specialists. This may help
to expedite the lengthy process to a correct
diagnosis.
Additional resources for patients and 2.
caregivers to navigate the emotional impact
of rare diseases, particularly for those where
the treatment outlook is limited.
There is a tremendous amount of emotional
burden involved with fi nding credible
information and qualifi ed specialists as
patients and their caregivers fi ght and pay for
care for an uncommon ailment. Resources or
care coordinators that help to navigate this
process or ease the emotional burden are
warranted.
A need for more research to expand the 3.
current rare disease body of knowledge.
Additional academic and clinical research will
ultimately offer patients increased options,
and provide physicians with more tools to
diagnose patients, all while equipping payors
with evidence-based guidelines upon which
to base coverage decisions.
Report Findings Call for the Following:
3
3

Patient/Caregiver Sample
While there are approximately 7,000 different
types of rare diseases and disorders worldwide,
the survey aimed to look at the commonalities in
health,  nancial, and psycho-social experiences
shared by those living with a rare disease and
their loved ones.
A total of 144 patients and 132 caregivers •
responded in the US. In the UK, 487 patients
and 124 caregivers responded
A total of 466 rare diseases were represented •
by the survey respondents (178 in the US,
288 in the UK)
The types of rare diseases represented by •
the sample varied in prevalence and included
blood, neurologic, immune, chromosome,
metabolic disorders, and rare cancers
Rare diseases ranged between those where •
treatment is available (de ned as approved
drugs, biologics, or devices that help to
manage or control the disease) and those
where there are no treatments. A majority of
patients surveyed (60% in the US, 71% in
the UK) said there was an existing treatment
for their rare disease. More than half of
caregivers surveyed reported their loved one
suffered from a rare disease for which there
was no treatment (56% in the US, 51%
in the UK)
Physician Sample
The survey looked at physician experiences
treating and managing patients with rare
diseases.
United States
Respondents included 50 US physicians with
the following classi cations:
Internal medicine/general practice physicians •
(66%), pediatricians (8%), cardiologists (8%),
hematologists (6%), nephrologists (6%),
allergists (4%), and a neurologist (2%)
Worked in private practice (56%)•
Belonged to a group practice with at least •
three physicians (34%)
Had a full or part ownership in the practice •
(48%)
Were board certi ed in a given specialty •
(94%)
Less than 10% of physicians’ patient bases •
had a rare disease (92%)
United Kingdom
Respondents included 50 UK physicians with
the following classi cations:
Pediatricians (50%), cardiologists (16%), •
hematologists (12%), internal medicine/
general practitioners (10%), neurologists
(8%), a nephrologist (2%), and an OB/GYN
(2%)
“These survey fi ndings suggest that whether in
the US or UK, more research, information and
education could help to alleviate some of the
obstacles we see in getting patients the care
they need.”
Dr. Christian J. Hendriksz, Clinical Lead, Adult Inherited Metabolic
Disorders, Salford Royal NHS Foundation Trust
Methodology: The Data Collection
4

Belonged to a specialist register (78%), •
followed by cardiologists (16%), and
hematology specialists (12%)
Had a hospital-based practice (94%)•
Less than 10% of physicians’ patient bases •
had a rare disease (78%)
Payor Sample
The survey looked into payor perspectives
providing coverage and services for rare
disease patients.
United States
Respondents included 20 payors with the
following classi cations:
Worked for a government health insurance •
provider (70%), private insurance providers
(30%)
Held director-level positions (60%) while the •
remainder held higher than a director-level
position (40%)
United Kingdom
Respondents included 20 payors with the
following classi cations at the time of  elding
(of note, the National Health Service (NHS) is
currently reorganizing and classi cations may
change):
Worked at a Primary Care Trust (10%) or •
other Care Trust (65%), which combines
national and local health agencies; the
Department of Health (15%); and the
Strategic Health Authority (10%)
Held a management position (60%)•
Thought Leader Sample
The survey looked into thought leaders'
perspectives (e.g., policymakers, researchers,
advocates) on the key issues/challenges facing
the rare disease community in areas such as
diagnosis, scienti c understanding, treatment
options, and social services.
Respondents included 11 thought leaders in
the US and  ve thought leaders in the UK.
Feedback from these surveys was used to help
support and reinforce the key rare disease gaps/
issues identi ed within the other surveys.
5
Hannah Ostrea, child who suffered from Gaucher disease type 2/3

According to physicians surveyed,
as compared to their experience in
managing more common diseases:
The majority of physicians reported it is more
difcult to address the needs of a rare disease
patient in a typical ofce visit.
Nearly all physicians stated more ofce visits
are required to diagnose a rare disease patient.
The majority of physicians said it takes more
ofce visits to adequately address symptoms.
Around half of physicians said that medical
professional organizations do not give enough
attention to rare diseases.
More than half of physicians stated there aren’t
enough opportunities to network with other
physicians who treat rare diseases.
While it may be necessary to coordinate with
other physicians when managing a patient with
a rare disease, the majority of physicians said
they found it difcult to do so.
According to patients and caregivers
surveyed:
Around half of patients with a rare disease
and their caregivers stated they received
conicting information from different healthcare
professionals about treatment options.
More than half of patients and caregivers
stated they needed to provide their healthcare
professionals with information on their rare
disease.
Combined Summary of Key Findings
THEME 1: There is a Lack of Resources and Information to
Address Rare Diseases
Physicians (both primary care and specialists) have limited resources and information to properly
diagnose/manage patients with rare diseases as compared to more common diseases seen.
92%
in the US
88%
in the UK
54%
in the US
62%
in the UK
67%
in the US
62%
in the UK
60%
in the US
50%
in the UK
98%
in the US
96%
in the UK
92%
in the US
88%
in the UK
46%
in the US
50%
in the UK
76%
in the US
88%
in the UK
Delays in Diagnosis
According to patients surveyed, it takes: According to patient/caregiver respondents, in order to
get a proper diagnosis, a patient typically visits up to
for a patient with a rare disease to
receive a proper diagnosis
on average 7.6 years in the US 8 physicians: 4 primary care and 4 specialists
on average 5.6 years in the UK
and receives 2 to 3 misdiagnoses

The costs associated with rare
diseases are rising:
The journey to diagnosis and beyond comes •
with a steep price tag for many coping
with a rare disease. This long road, which
frequently includes numerous tests and
physician visits, can become  nancially
overwhelming, particularly for those in the
US. Payor respondents cited several factors
as contributing to the higher costs of care for
rare disease patients, as compared to more
common diseases, including:
More diagnostic tests (100% in the US, •
80% in the UK)
More costly diagnostic tests (100% in the •
US, 90% in the UK)
More visits to specialists (95% in the US, •
95% in the UK)
More mental health support needed (90% •
in the US, 75% in the UK)
• Nearly all payors surveyed reported that
treatment for patients with rare diseases
is relatively more expensive compared to
treatments for other patients with more
common diseases (95% in the US, 100%
in the UK) and costs are also rising more
rapidly (90% in the US, 85% in the UK)
The cost of medical care and the multitude •
of services associated with managing the
disease place a greater  nancial burden in
the US than the UK
Although 90% of patients surveyed had •
health coverage in the US:
55% of US respondents incurred direct medical
expenses not covered by insurance compared
to 18% in the UK not covered by the National
Health Service.
37% borrowed money from family and/or friends
to pay for expenses in the US compared to only
21% in the UK.
Payors fi nd it diffi cult to determine
how rare diseases should be covered
due to the lack of standards and
guidelines:
Almost all payors surveyed indicated there •
is less information/data available to help
determine the standards of care for rare
diseases (95% in the US, 90% in the UK)
and that it is more dif cult to decide what
coverage to provide for patients (90% in the
US, 85% in the UK)
THEME 2: The Economic Impact of Diagnosing and Managing
Rare Diseases Is Signifi cant
55%
in the US
18%
in the UK
37%
in the US
21%
in the UK
7

According to physicians surveyed,
as compared to their experience in
managing more common diseases:
Rare disease patients reported their disease
caused:
Depression (75% in the US, 69% in the UK)•
Anxiety and stress (86% in the US, 82% in •
the UK)
Isolation from friends/family (65% in the US, •
57% in the UK)
Less interaction with friends/family (70% in •
the US, 68% in the UK)
Worry based on future outlook of disease •
(90% in the US, 91% in the UK)
Worry based on lack of information available •
on disease (83% in the US, 81% in the UK)
Caregivers of rare disease patients felt similar
psycho-social concerns and feelings of:
Depression (72% in the US, 65% in the UK)•
Anxiety and stress (89% in the US, 88% in •
the UK)
Isolation from friends/family (64% in the US, •
54% in the UK)
Less interaction with friends/family (55% in •
the US, 45% in the UK)
Worry based on future outlook of disease •
(97% in the US, 94% in the UK)
Worry based on lack of information available •
on disease (87% in the US 84% in the UK)
For those rare disease patients where
treatment options are limited, overall they
worry more, feel more depressed, interact
less, and feel more isolated from family
and friends compared to patients with
rare diseases for which there are available
treatments.
According to survey results, health-related
quality of life for patients with a rare disease is
estimated to be about half of what it would be if
the patients were healthy.
The health-related quality of life is signi cantly
lower for those with rare diseases for which
there is no treatment.
THEME 3: Rare Diseases Take a Major Emotional Toll on Patients/Caregivers
Rare diseases have a considerable emotional impact on patients and caregivers, particularly for those
where the hope of treatment is minimal.
The health-related quality of life is
signifi cantly lower for patients suffering
from a rare disease compared to patients
who are otherwise healthy; the quality of
life is even lower for those where there is
no treatment available.
44%
in the US
58%
in the US
50%
in the UK
60%
in the UK
8

Key Insights
In the past few decades, increased awareness
and the advent of programs speci cally designed
to encourage the development of treatments for
rare diseases has led to some improvements in
diagnosis, treatment, and overall care. Despite
this progress, there is still an urgent need to
better understand the obstacles patients and
caregivers within the rare disease community
face, so appropriate measures can be taken to
address gaps in care. Challenges extend beyond
the disease itself. These challenges, which can at
times be overwhelming, include the following:
Finding appropriate medical care during the •
many years it often takes to receive a correct
rare disease diagnosis and locating hard-to-
 nd specialists post-diagnosis
Handling the  nancial aspects of a rare •
disease, which can be exacerbated by bills
for special care, travel to  nd specialists and,
for some, the inability to work while managing
their disease
Coping with the emotional challenges a rare •
disease presents, which include feelings of
isolation and uncertainty about the future
Patient/Caregiver Findings
“Finding a doctor that
can treat me is the
most diffi cult part. I
have traveled to many
states looking for a
qualifi ed doctor.”
US patient with Multiple Hereditary
Exostosis, a rare disease that
causes noncancerous bone tumors
that can later become cancerous
The Mills sisters, both diagnosed with CADASIL syndrome
9

Long, Slow Road to Diagnosis
For many, being diagnosed with a rare disease isn’t the beginning of their journey. Often the journey
began years earlier with a symptom, an unyielding pain, or a constellation of signs that could not be
explained. Multiple doctor visits often accompanied by ad-hoc Internet research direct a path for the
rare disease patient that is usually far from linear.
Survey Results
As a result of these challenges, on average, it takes 7.6 years
in the US and 5.6 years in the UK for a patient with a rare disease
to receive the proper diagnosis, based on survey results. Along the
way, the average patient visits four primary care doctors and four specialists
and receives two to three misdiagnoses. Those who care for people with rare
diseases also reported delays and missteps. In both the US and in the UK,
caregivers surveyed said diagnosis took an average of 3 years after seeing a total
of seven or eight doctors.
?
Sometimes there’s no GPS signal.
When relatively few people have a disease, information is
frequently scarce, forcing many patients to navigate with little
guidance. This leaves many patients and their caregivers alone
in a maze of roadblocks and detours, which includes diffi culty
fi nding a knowledgeable specialist, dealing with fi nancial burdens,
as well as handling emotional diffi culties.
At times the directions are confl icting.
General practitioners may miss the indicators of a rare disease
because they may have never seen a particular rare disease
before or the disease presents the signs and symptoms of a more
common disease. This misdirection can lead to a missed rare
disease diagnosis or to misdiagnosis.
Road conditions lead to further delays.
Often the healthcare system doesn’t allow doctors to easily
share information or collaborate with each other, even with a
patient’s consent. A test taken at one center or an observation
from one physician may not make its way to the next medical
professional.
10

Patients and Caregivers Reported that They Must Wear Many Hats
Often, when dealing with a rare disease, patients and caregivers  nd themselves wearing multiple hats
and juggling several roles in an effort to receive optimal care. These include playing multiple roles:
“Getting a correct diagnosis was so diffi cult, stressful and
humiliating at times. I found that doctors did not like to listen
to my take on things, they did not like my asking relevant
questions or expressing concerns, looked only at specifi c
test results and if these were not fi tting into the categories of
their particular expertise or discipline, they would dismiss me.
...There was also a lot of ‘passing’ me from doctor to doctor
without an overall coordinator of care.”
UK patient with Mixed connective tissue disease, an autoimmune rare disease
which has the signs and symptoms of lupus, scleroderma, polymyositis, and
rheumatoid arthritis
Researcher Advocate
Care Coordinator
Researcher. A lack of information about many rare diseases is a major
obstacle. Often, to obtain answers, the role of the researcher falls on those
dealing with the disease or their caregiver, as they scour the Internet for
assistance with diagnosis, possible treatments, specialists, and information
on studies as they seek support from others  ghting a similar battle. In
fact, in both the US and UK, more than 60% of patients and caregivers
surveyed responded that they needed to provide health care professionals
with their own information on their rare disease (67% in the US, 62% in the
UK). When it comes to a disease that very few patients have, doctors often
can’t provide answers to the many questions that arise, such as:
What causes this disease?
Is this something that I could pass along to
my children?
Is this symptom related to the disease?
What treatments are available to help with
symptoms?
How will the disease progress?
Are there treatments that can slow the
disease progression?
Will it help to alter my diet or other
activities?
Is there a support group in my area?
Is there an organization online for this
disease?
How can I participate in a research study?
67%
in the US
62%
in the UK
11

Care Coordinator. Managing multiple appointments, taking detailed
notes during appointments, and relaying information from one medical
professional to another often falls on the patient or caregiver. When a
disease is unfamiliar, there will be many questions. Keeping records of
the answers, planning the next steps, and handling con icting advice can
feel like a full-time job and can quickly become overwhelming. Within the
survey, 60% of US patients/caregivers and 50% of UK patients/caregivers
said they received con icting information from different healthcare
professionals about treatment options for their rare disease.
Advocate. When there’s no clear roadmap, the patient
or caregiver must often chart his or her own course.
This frequently involves seeking additional medical
opinions from various healthcare professionals,
appealing to payors for unconventional care, resolving
billing issues, and becoming a self-advocate as well as
an advocate for others suffering from a similar ailment.
The role of advocacy is particularly crucial in the rare
disease community. Because of the small number of
people living with a particular disorder, patients and
caregivers feel the added pressure to educate others
about the disease, often times including medical
professionals. At times, this advocate role will involve
lobbying government for care or organizing a support
group for others with a similar rare disease.
60%
in the US
50%
in the UK
Signifi cant Financial Costs of Care
“I had to end my career as a paralegal as the pain
and medication associated with the disease made
it impossible for me to work a full-time job. I was
forced onto disability, causing fi nancial hardship.”
US patient with Wegener’s granulomatosis, a rare disease that causes blood
vessels to infl ame making it diffi cult for blood to fl ow
The lengthy journey to diagnosis and ongoing disease management create a signi cant  nancial
burden for patients and caregivers coping with a rare disease. This is particularly true in the US,
according to the survey  ndings. Medical costs and services were considered a “major burden” by
half of those in the US, double the rate reported in the UK.
Hannah Ostrea, child who suffered from Gaucher disease
Type 2/3, and her care team
12

The Emotional Toll on Patients and Caregivers
“The most diffi cult experiences have been my
anxiety, depression, the inability to cope with
stressful situations, and physical complaints
associated with my disorder.”
US patient with Late-onset congenital adrenal hyperplasia, a rare genetic disease
that can result in excessive hair growth, absent periods, infertility, and hair loss in
women and early beard growth, small testes, and short stature in men
On each fi nancial question included within the survey, patients and caregivers in the US fared
signifi cantly worse than those in the UK:
These  nancial outlays occurred despite the fact that 90% of patients/caregivers in the US have insurance
or another program that pays for all or part of the medical expenses associated with the rare disease.
Financial Consequences US UK
Had to use savings to pay for medical expenses 53% 31%
Incurred direct medical expenses not covered
by insurance/National Health Service 55% 18%
Borrowed money from family and/or
friends to pay for expenses 37% 21%
Sought help from charity or public assistance 34% 18%
Negatively impacted credit score 32% 10%
Used retirement funds to pay for expenses 23% 10%
13

Emotional Impact of Rare Disease on Patients
0 20 40 60 80 100
Feelings of depression
Feelings of
anxiety/stress
Less interaction with
friends/family
Isolation from
friends/family
Worry about how
their health will
change in the future
Lack of available
information on
rare disease
caused worry
Felt they had no one
to turn to in the
medical system for
information/support
75%
69%
86%
82%
70%
68%
65%
57%
90%
91%
83%
81%
65%
53%
T: 47% UT: 67%
T: 79% UT: 88%
T: 79% UT: 88%
T: 53% UT: 66%
T: 64% UT: 77%
T: 66% UT: 75%
T: 81% UT: 82%
T: 59% UT: 74%
T: 80% UT: 86%
T: 89% UT: 86%
T: 63% UT: 68%
T: 64% UT: 79%
T: 71% UT: 81%
T: Treatable UT: Untreatable
T: 84% UT: 89%
US UK
As with any illness, there are added emotional burdens, such as worry, stress, and anxiety. These
burdens are compounded by uncertainty, the lack of available information and resources, economic
strain, and added responsibilities for many patients with rare diseases and their caregivers. Patient
and caregiver respondents reported the following emotional dif culties as a result of having to manage
or take care of a loved one with a rare disease.
As illustrated, the highest emotional burden can be seen in those with a rare disease where there are
no available treatments. Overall, compared to patients with rare diseases where there are available
treatments, patients with a rare disease with no treatment worry more, feel more depressed, interact
less with friends and family, and feel more isolated from friends and family.
14

Emotional Impact of Rare Disease on Caregivers
Feelings of depression
Feelings of
anxiety/stress
Less interaction with
friends/family
Isolation from
friends/family
Worry about how
their health will
change in the future
Lack of available
information on
rare disease
caused worry
Felt they had no one
to turn to in the
medical system for
information/support
0 20 40 60 80 100
72%
65%
89%
88%
55%
45%
64%
54%
97%
94%
87%
84%
64%
55%
T: 41% UT: 68%
T: 84% UT: 84%
T: 97% UT: 92%
T: 39% UT: 68%
T: 39% UT: 51%
T: 66% UT: 63%
T: 89% UT: 87%
T: 60% UT: 68%
T: 86% UT: 88%
T: 97% UT: 97%
T: 53% UT: 72%
T: 43% UT: 65%
T: 69% UT: 74%
T: Treatable UT: Untreatable
T: 91% UT: 88%
US UK
15

Patients with a rare disease and those who care for them reported that their overall quality of life was
lower when compared to those who are healthy. Some of the most dramatic differences on quality of
life were observed among patients with rare diseases for which there are no treatments available. This
is the case when compared to an otherwise healthy person and even when compared to those with
more common, serious diseases such as coronary heart disease, HIV, stroke, or arthritis.
*To measure health-related quality of life, a scale called the Health Utilities Index™ (HUI) was used. By rating vision, hearing, speech,
walking, dexterity, happiness, cognition, and pain, the scale calculated a score, that can be compared to someone in perfect health. For
example, a score of 1.0 is for someone with optimal health, 0.0 would represent death and a score of 0.60 suggests a quality of life that is
40 percent lower than they would have if not for their health issues.
Health-Related Quality of Life*
100
80
60
40
20
0
44%
lower50%
lower
Treatable
rare disease
58%
lower
Untreatable
rare disease
41%
lower
Multidrug-
resistant HIV
44%
lower
Coronary
heart disease
(US only)
46.2%
lower
Stroke
23.5%
lower
Arthritis
Healthy
person
US UK More common,
serious diseases
“Clearly, there are substantial fi nancial and emotional burdens of rare
diseases on patients and their families. A largely unrecognized issue
is the inordinate amount of time it takes to establish a clear diagnosis
for patients with rare diseases and the stress that this causes. Patients
often consult with a wide range of clinical practitioners over a period of
years before receiving the appropriate information about their condition.”
Mike Drummond, Professor of Health Economics, University of York
16
Quality of Life of Rare Disease Patient When Compared to Healthy
Subject and More Common, Serious Diseases
60%
lower

Key Insights
When it comes to assessing the needs of the
rare disease community, physicians have a
unique vantage point. As medical professionals,
they encounter a range of conditions and
symptoms while treating numerous patients. On
the front line of care, doctors must stay abreast
of current research while serving as the delivery
point and, at times, as an intermediary between
patients and payors.
Given the complexity and inherent challenges
of diagnosing and managing rare diseases, it
is important to grasp the physician perspective
– across the spectrum from primary care
physicians to specialists. A key issue many
physicians face when treating patients with rare
diseases includes the limited resources and
information to properly diagnose and manage
patients with rare diseases when compared to
more common diseases:
Rare disease patients require longer and •
more frequent visits with their physician(s),
making it dif cult to provide needed care in
the allotted appointment time
Physicians feel that medical professional •
organizations do not provide suf cient
attention to rare diseases and do not have
enough opportunities to network with other
physicians who treat rare diseases
To treat rare disease patients, doctors must •
coordinate more often with other treating
specialists and healthcare providers
Physician Findings
“Rare diseases require
a great deal of time,
fi nancial cost, and
patient education.
Additional research
funding is sorely
needed.”
US physician
Jeff, Renee, and Matthew Wuchich (diagnosed with Alternating hemiplegia of childhood)
and Dr. Mohamad Mikati (pediatric neurologist) at Duke Children’s Hospital
17

Barriers
Percentage of US
physician respondents
that agreed with
statement
Percentage of UK
physician respondents
that agreed with
statement
More dif cult to address the needs
of a rare disease patient in
typical of ce setting 92% 88%
More of ce visits are
required to diagnose 98% 96%
More of ce visits needed to
adequately address symptoms 92% 88%
Medical professional organizations do
not give enough attention
to rare diseases 46% 50%
Aren’t enough opportunities to
network with other physicians
who treat rare diseases 54% 62%
Dif cult to coordinate with other
physicians when managing a patient with
a rare disease 76% 88%
Adequate and effective treatments are
less available once patient is diagnosed 86% 90%
Survey Results
Top Barriers Reported to Offering Quality Care to Patients with Rare Diseases
Lack of Time for Diagnosis and Care
“These kids and families have tremendous needs. ... It is
diffi cult to spend the needed time to address all of the
needs of children with complex medical conditions.
… More patients need to be seen in a day and this limits
the time available for all patients including those with rare
diseases.”
US physician
18

Because physicians see those suffering from rare
diseases infrequently, they  nd themselves faced
with more questions, yet fewer answers. Compared
to patients with diseases that are as serious, but
more common, rare disease patients require:
More of ce visits to receive an accurate •
diagnosis and proper care
Longer of ce visits, as there is less available •
information and more need for patient education
Additional support services, such as patient •
education services, mental health services and
referrals to support organizations
Once a correct diagnosis is  nally made – which
patients reported can take more than  ve years –
physicians reported that adequate and effective
treatments are less available, which also adds to the
time doctors spend trying to  nd solutions for their
patients.
Rare Disease Treatment Requires More Resources
“There is a lack of local
experience, therefore
patients have to travel
long distances to see
someone with the
expertise that is needed
to treat them.”
UK physician
Resources, like time, are  nite. Many physicians
stated their practices must dedicate more of their
limited resources when managing a patient with
a rare disease. Providing these extra support
services increases the strains on their time.
28% of US physicians and 42% of UK physicians
surveyed report that their practice must use their
non-physician staff, such as nurses, counselors
or other healthcare professionals to educate rare
disease patients on managing their disease.
44% of US physicians and 42% of UK physicians
surveyed provide written materials to patients that
explain guidelines for recommended care. These
wellness services were particularly common
among doctors who work at large institutions,
such as medical schools and hospitals.
Most physicians in both the US and in the UK
agreed that it is often more labor intensive to
administer claims and to code of ce visits and
procedures for rare disease patients.
28%
in the US
44%
in the US
66%
in the US
42%
in the UK
42%
in the UK
82%
in the UK
19

In many cases, patients with a rare disease
need to see multiple physicians before getting
correctly diagnosed and also need to obtain care
from multiple practitioners simultaneously, in
order to address all the symptoms/complications
associated with their disease. These factors all
require communication and coordination among
the medical professionals on a patient’s care
team.
However, a majority of physicians who responded
to the survey stated that they  nd it more dif cult
to coordinate with other providers who are all
managing the same patient with a rare disease
(76% in the US, 88% in the UK).
Because of the nature of the category, many
physicians (both primary care and specialists)
see rare disease patients – especially those
with the same disorder – infrequently. Therefore,
individually, they seldom amass suf cient
experience in all phases of diagnosis, treatment,
and supportive care to become experts on a
speci c disorder. This leads them to call for an
increase in education and support throughout
the medical community to assist in gathering and
sharing rare disease information with each other.
However, fewer than half of physicians surveyed
thought that medical professional organizations
provide suf cient attention to rare diseases (46%
in the US, 46% in the UK). Likewise, fewer than
half thought that there were enough opportunities
to network with other physicians who treat rare
diseases (46% in the US, 38% in the UK).
More Coordination Needed Throughout Medical Community
More Awareness and Support Needed
“It’s hard to coordinate
care for patients with
specialists due to time
constraints.”
UK physician
The challenge of staying abreast of rare disease developments
and being aware of diagnostic criteria also arose as a concern
for physicians surveyed.
11
“It is diffi cult to stay up to date regarding rare
diseases that I see infrequently compared with
most of my general pediatric practice.”
UK physician
“You never see enough of them [patients with
rare diseases] to build up the experience.”
US physician
20

Key Insights
Payors are in a unique position as their
decisions impact both patients’ care and
physician treatment decisions. Payors can
provide valuable insights into the reasons
how and why certain coverage decisions are
made. For many rare diseases, evidence-based
treatment guidelines may not be adequate and,
in some cases, non-existent, which makes it
harder for payors to make coverage decisions.
Other barriers payors  nd when making
rare disease coverage decisions include the
following:
The lack of standards related to rare •
disease care
The costs of care, which continue to rise, •
leading to uncertainty about future pricing
The increased level of care rare disease •
patients need, which also translates to
higher costs
In the US in particular, these high costs strain •
an already stretched healthcare system
Payor Findings “There is a reluctance
of insurance
companies to pay for
certain treatments and
tests for rare diseases
they feel are not
proven.”
US payor
21

“It is diffi cult to predict healthcare costs and what
interventions may be required over a lifetime.”
US payor
Survey Results
Across the spectrum, patients, those who care
for them, physicians, and payors all agree that
the cost of rare disease care is a major concern
and obstacle to care. This was seen in responses
from payors in the US, who represented both
government and private insurers, as well as those
in the UK, who represented the government-
sponsored health system.
Despite the vast differences in healthcare
systems, payors in the US and UK agreed almost
unanimously that compared to treatment of
more common diseases of comparable severity,
treating those with rare diseases is relatively
expensive (95% in the US, 100% in the UK) and
costs are rising more rapidly (90% in the US, 85%
in the UK).
More diagnostic
tests needed
Diagnostic tests
are more costly
More visits to
specialists required
Increased need
for mental health
support services
0 20 40 60 80 100
100%
100%
95%
90%
80%
90%
95%
75%
US UK
22
Payor-Cited Factors Contributing to High Costs of Rare Diseases

Factors
Percentage of US
Respondents that
Agreed with Statement
Percentage of UK
Respondents that
Agreed with Statement
Rare disease patients require more
prescription drugs 90% 30%
Rare disease patients have an increased
need for customer service support 90% 45%
Rare disease patient care puts a strain
on the healthcare system 90% 45%
It is dif cult to predict the cost of caring
for rare disease patients in the future 95% 70%
Rare disease patients are likely to reach
lifetime caps on coverage expenditures
(US only) 100% n/a
Compared to patients with common
diseases of comparable severity, rare
disease patients are likely to be denied
coverage (US only)
90% n/a
Not surprisingly, because of vastly different healthcare systems, several factors impact US payor
decisions more so than those in the UK.
US and UK: Different Perspectives
When dealing with one disease that has an
impact on so few people, payors often  nd
themselves in uncharted territory. Just as the lack
of information confounds patients and doctors,
it also leaves payors to make decisions without
established guidance.
The shortage of information led almost all
payors surveyed to indicate that compared to
common diseases of comparable severity, there
is less information available to help determine
the standards of care for rare diseases (95%
in the US, 90% in the UK). They also reported,
overwhelmingly, that it is more dif cult to decide
what coverage to provide for rarely seen diseases
(90% in the US, 85% in the UK).
More Awareness and Support Needed
“The rarity of a disease
inevitably means a
lack of expertise, a
lack of understanding
of the needs of
patients and no clearly
identifi ed treatment
pathways or packages
of care.”
UK payor 23

16p11.2 deletion syndrome
1q21.1 microdeletion syndrome
1q43 chromosome deletion syndrome
22q11.2 duplication syndrome
Addison’s disease
Alexander disease
Alopecia, epilepsy, pyorrhea, mental subnormality
Alpha 1-antitrypsin de ciency
Ankylosing spondylitis
Aortic valves stenosis of the child
Asbestosis
Ataxia telangiectasia
Autosomal-Dominant Alport syndrome
Bannayan-Riley-Ruvalcaba syndrome
Basal cell nevus anodontia abnormal bone
mineralization
Basilar migraine
Beckwith-Wiedemann syndrome
Behçet’s disease
Benign paroxysmal positional vertigo
Birdshot chorioretinopathy
Bone cancer
Bowen’s disease
Breast cancer, childhood
Bronchiolitis obliterans
Bicuspid heart valve
CADASIL syndrome
Cancer of the perineum
Carney triad
Caroli disease
Cataract and cardiomyopathy
Appendix
Areas for Future Research
Based on the  ndings uncovered in this report, below are some areas to consider for future research:
Additional focus on cultural or regional differences of the impact of rare diseases •
Further research on the impact of rare diseases on patients with treatable rare diseases compared •
to those ultra-rare conditions where there aren’t any treatments available
Further explore the primary care physician perspective on rare disease diagnosis and management •
compared to the perspective of specialists to identify major discrepancies and gaps
References
U.S. National Library of Medicine, National Institutes of Health website. “Rare Diseases.” http://1.
www.nlm.nih.gov/medlineplus/rarediseases.html. Accessed March 18, 2013.
World Health Organization website. “Bulletin of the World Health Organization: Coming together to 2.
combat rare diseases.” http://www.who.int/bulletin/volumes/90/6/12-020612/en/. Accessed March
18, 2013.
National Institutes of Health website. “Of ce of Rare Disease Research.” http://rarediseases.info.3.
nih.gov/AboutUs.aspx. Accessed March 18, 2013.
Rare Disease UK website. http://www.raredisease.org.uk/. Accessed March 18, 2013.4.
Global Genes website. “RARE Facts and Statistics.” http://globalgenes.org/rarefacts/. Accessed 5.
March 18, 2013.
List of Rare Diseases
Patients and families affected by the following rare diseases responded to the survey:
US
24

C. diff
CDKL5
Cerebellar ataxia
Charcot-Marie-Tooth disease type 1A
Chromosome 16q deletion
Chronic in ammatory demyelinating
polyneuropathy
Chronic myeloid leukemia
Chronic recurrent multifocal osteomyelitis
Common variable immunode ciency
Complex regional pain syndrome
Congenital heart block
Cowden’s disease
Cutaneous mastocytosis
CVID and MGUS
Cystic  brosis
Cystic hygroma
Cystinuria
D-2 hydroxyglutaric aciduria
Dandy Walker syndrome/malformation
Desminopathy
Devic disease
Diabetes hypogonadism deafness mental
retardation
Diabetes mellitus, transient neonatal
Diabetes persistent mullerian ducts
Diabetic mastopathy
Diamond-Blackfan anemia
DICER1-related pleuropulmonary blastoma
cancer predisposition syndrome
Distal chromosome 18q deletion syndrome
Dominant optic atrophy
Duchenne muscular dystrophy
Dysautonomia-like disorder
Ehlers-Danlos syndrome
Eosinophilic esophagitis
Familial periodic paralysis
Fibrous dysplasia
Friedreich ataxia
Gardner syndrome
Gastric duplication cysts
Gaucher disease
Gitelman syndrome
Glycogen storage disease type 2
Granulomatous disease of unknown etiology
Harlequin ichthyosis
Heart defect, tongue hamartoma and
polysyndactyly
Hemophilia A, acquired
Hemophilia A, congenital
Hereditary coproporphyria
Hereditary Spastic Paraplegia
Heterotaxy syndrome
Hirschsprung’s disease
Homocystinuria
Hyper-IgD syndrome
Hypereosinophilic syndrome
Hyperglycinemia, isolated nonketotic type 1
Hypocalcemia, autosomal dominant
Infantile spasms
Isovaleric acidemia
Joubert syndrome
Joubert syndrome with ocular anomalies
Juvenile dermatomyositis
Juvenile-onset  bromyalgia, Ehlers-Danlos
syndrome
Kleefstra syndrome
Klippel-Feil syndrome
Langerhans cell histiocytosis
Late Infantile Batten disease
Late-onset congenital adrenal hyperplasia
Leber's congenital amaurosis
Legg-Calve-Perthes disease
LEOPARD syndrome
Leukoencephalopathy with vanishing white matter
Lupus
Lupus anticoagulant
Mal de debarquement
Maple syrup urine disease
Marfan syndrome
25

Metastatic extra adrenal paraganglioma and
metastatic diffuse sclerosing variant of thyroid
cancer
Microscopic polyangiitis
Mitochondrial genetic disorders
Mixed connective tissue disease
Moebius syndrome
Monogenic diabetes (MODY 2)
Morgellons
MPS III (San lippo syndrome)
Mucha-Habermann disease
Mucolipidosis III alpha/beta
Mucopolysaccharidosis
Multiple chemical intolerance
Multiple chemical sensitivity
Multiple hereditary exostoses
Multiple myeloma
Myasthenia gravis
Nephropathic cystinosis
Neuro medulloblastoma
Neurocutaneous melanosis
Neuromyelitis optica spectrum disorder
Neuronal ceroid lipofuscinoses
Non ketotic hyperglycinemia syndrome
Non-Hodgkin lymphoma, childhood
Nonketotic hyperglycinemia
Oculofaciocardiodental syndrome
Ollier disease
Opsoclonus myoclonus ataxia
Opsoclonus myoclonus syndrome
Oral facial digital syndrome
Oral facial digital syndrome 1
Ornithine transcarbamylase de ciency
Pachygyria
Pallister-Killian syndrome
Pelizaeus-Merzbacher disease
Peripheral neuropathy
Phelan-McDermid syndrome
Pheochromocytoma
Pompe disease
Pontocerebellar hypoplasia with spinal muscular
atrophy (VRK1 mutation)
Premature ovarian failure, familial
Primary Immunode ciency Disorder (PIDD)
Progressive pseudorheumatoid chondrodysplasia
Pseudoachondroplasia
Pseudomyxoma peritonei
Pseudotumor cerebri
Pyruvate kinase de ciency
Ramsay Hunt syndrome
Relapsing polychondritis
Rhabdomyosarcoma alveolar
San lippo syndrome A
Sarcoidosis
Schmid-Fraccaro syndrome/Cat Eye syndrome
Sheehan’s syndrome
Skin cancer, non-melanoma, childhood
Soft tissue sarcoma
Stiff person syndrome
Systemic mastocytosis
Thyroid cancer, medullary
Trimethylaminuria
Trisomy 18
Tuberous sclerosis
Ulcerative colitis
Unbalanced chromosomal translocation between
7 & 10
Undiagnosed neurometabolic disorder
Unidenti ed genetic syndrome
Vasovagal re ex
WAGR syndrome
Wegener’s granulomatosis
Williams syndrome
Wilms’ tumor
UK
3-beta-hydroxysteroid dehydrogenase de ciency
Acoustic neuroma
Acquired angioedema
26

Acquired C1 esterase de ciency due to
autoimmune antibodies
Acrodermatitis
Acromegaly
ACTH + Androgen de ciency
Action myoclonus-renal failure syndrome
Acute articular rheumatism
Acute intermittent porphyria
Addison's disease
Adrenoleukodystrophy X-linked
Aglossia and situs inversus
Alopecia, epilepsy, pyorrhea, mental subnormality
Alpha 1-antitrypsin de ciency (A1AD)
Alström syndrome
Alzheimer disease type 1
Amyotrophic lateral sclerosis
ANCA-negative vasculitis possibly polyarteritis
nodosa
ANCA-postive vasculitis
Aniridia
Aplastic anemia
Are exia, pes cavus, optic atrophy, and
sensorineural hearing loss
Ataxia (unknown type)
Atypical hemolytic-uremic syndrome
Autosomal dominant optic atrophy, hearing loss,
and peripheral neuropathy
Autosomal dominant spinocerebellar ataxia type 6
Bardet-Biedl syndrome
Barth syndrome
Basilar migraine
Batten disease
Behçet’s disease
Birdshot chorioretinopathy
Blood clotting factor de ciency
Bone cancer
Brain tumor, adult
Brittle bone disease
Brown-Vialetto-Van Laere syndrome
C-ANCA positive cerebral vasculitis
C1 esterase de ciency and angioedema (HAE)
C1 protein inhibitor de ciency
Carcinoid syndrome
Caroli disease
Cataract, glaucoma
CDKL5 disorder
Central nervous system vasculitis
Cerebellar ataxia
Cerebellar degeneration
Cerebral vasculitis
Chiari malformation
Cholangiocarcinoma
Chondrosarcoma
Chromosome 10p duplication
Chromosome 12q deletion
Chromosome 13q deletion
Chromosome 15q deletion
Chromosome 15q duplication (partial octasomy of
chromosome 15 – believed to be the only one in
the world that we know of)
Chromosome 1q21.1 duplication syndrome
Chromosome 9p deletion
Chronic lymphocytic leukemia
Chronic mucocutaneous candidiasis
Chronic myeloid leukemia
Chronic progressive external ophthalmoplegia
plus
Churg-Strauss syndrome
CIDP
CNS vasculitis
Cockayne syndrome
Common variable immunode ciency
Complex regional pain syndrome
Congenital toxoplasmosis
Congenital adrenal hyperplasia
Congenital chloride diarrhea
Congenital myasthenic syndrome – presumed,
unknown gene fault
Congenital sideroblastic anemia
Craniopharyngioma
27

Creutzfeldt-Jakob disease
Cri-du-chat syndrome
Crohn’s disease
Cushing’s syndrome
Cutaneous necrotizing vasculitis
Cystic  brosis
Cystinosis
Cystinuria
Dercum’s disease
Diabetes insipidus nephrogenic mental retardation
and intracerebral calci cation
Dopamine-responsive dystonia and vasculitis
Duchenne muscular dystrophy
Dystonia 5, dopa-responsive type
Ectodermal dysplasia
Ehlers-Danlos syndrome
Electrical hypersensitivity
Empty sella syndrome
Esophageal cancer
Essential thrombocythemia/PV (MPN)
Essential thrombocythemia
Fabry disease
Familial cerebellar ataxia
Familial prostate cancer
Friedreich’s ataxia
Furunculous myiasis
Gall bladder cancer
Gastrointestinal stromal tumors
Gerstmann syndrome
Giant cell arteritis
Gluten ataxia
Goldenhar syndrome
Gorlin-Goltz syndrome
Greig cephalopolysyndactyly syndrome
Group B strep disease in newborns
H-ABC syndrome
Hailey-Hailey disease
Hairy cell leukemia
Henoch-Schönlein purpura
Hereditary angioedema
Hereditary leiomyomatosis and renal cell cancer
(carcinoma) HLRCC fumarate hydratase
(FH) gene
Hereditary neuropathy with liability to pressure
palsies
Hermansky-Pudlak syndrome
Hilar cholangiocarcinoma
Holt-Oram syndrome
Hyperemesis gravidarum
Hypermobility syndrome
Hypocomplementemic urticarial vasculitis
syndrome
Hypogonadotropic hypogonadism
Hypohidrotic ectodermal dysplasia with
immunode ciency – NEMO gene
Hypomelanosis of Ito
Hypopituitarism
Idiopathic bilateral panuveitis
Idiopathic cerebellar degeneration
Idiopathic intracranial hypertension (IIH)
IGA nephropathy
Immune thrombocytopenia (ITP)
Inappropriate sinus tachycardia with ectopic and
SVT
Intracranial hypertension
Jansen type metaphyseal chondrodysplasia
Kabuki syndrome
Kallmann syndrome
Kartagener syndrome
Kleefstra syndrome
Klippel-Feil syndrome
Klippel-Trénaunay-Weber syndrome
Langerhans cell histiocytosis
Late onset ataxia
Late onset Tay-Sachs
Laurence-Moon Bardet-Biedl syndrome
Leukocytoclastic vasculitis
Lichen planopilaris and Oral lichen planus
Lichen sclerosus
28

Lipodystrophy, familial partial, type 2
Lowe oculocerebrorenal syndrome
Lupus nephritis
Lyme Neuroborreliosis
Lymphoma – AIDS related
Macrocephaly-capillary malformation
Maffucci syndrome
Ollie’s disease – they are unsure which at moment
Mal de debarquement syndrome
Manifesting carrier of Duchenne muscular
dystrophy
MECP2 duplication syndrome
Mesenteric panniculitis
Methylmalonic acidemia and homocystinuria cblC
type
Microdeletion 15q11.2
Microdeletion 17q21.31 Koolen-de Vries
syndrome
Microscopic polyangiitis
Microscopic polyangiitis with granulomatous
Microtia-Anotia
Mitochondria mutation/disorder
Mitochondrial myopathy with lactic acidosis
Mixed connective tissue disease
Motor neuro-ophthalmic disorders
Mucopolysaccharidosis type II
Multiple chemical sensitivity
Multiple endocrine neoplasia type 1
Multiple joint dislocations metaphyseal dysplasia
Myalgic encephalomyelitis
Myasthenia gravis
Myotonia congenita autosomal recessive
Nail patella syndrome
Narcolepsy
Neuro bromatosis type 1
Neuromyelitis optica spectrum disorder
Neuromyotonia; myasthenia gravis
Niemann-Pick disease
Nonfunctioning pituitary adenoma
Non-Hodgkin lymphoma, childhood
Nonketotic hyperglycinemia
Opsoclonus myoclonus syndrome
Osgood-Schlatters disease
Osteogenesis imperfecta
Palindromic rheumatism
Palmoplantar keratoderma
Panhypopituitarism
P-ANCA vasculitis
Panhypopituitarism
Panhypopituitarism X-linked
Paroxysmal nocturnal hemoglobinuria
PCOS
Pearl syndrome
Pearson’s syndrome
Pediatric multiple sclerosis
Periodic hypothermia
Periventricular nodular heterotopia
Permanent neonatal diabetes mellitus
Pernicious anemia
Phelan-McDermid syndrome
Phenylketonuria
Pheochromocytoma
Pitt-Hopkins syndrome
Pituitary dysfunction steroid dependant
Pituitary hormone de ciency, combined 3
Pituitary tumour
Polyarteritis nodosa
Polycythemia vera
Postural orthostatic tachycardia syndrome,
platybasia
Primary angiitis of the central nervous system
Primary ciliary dyskinesia
Primary sclerosing cholangitis
Protein S de ciency
Proteus syndrome
Pseudoachondroplasia
Pseudoxanthoma elasticum
Pseudomyxoma peritonei
Psychogenic non-epileptic seizures
29

Pulmonary vasculitis and membranous
glomerulonephritis
Ramsay Hunt syndrome
Rare chromosome disorder
Refsum disease, infantile form Zellweger
spectrum disorder
Relapsing polychondritis
Retinitis pigmentosa
Retinopathy aplastic anemia neurological
abnormalities
Rheumatoid vasculitis
Rosai-Dorfman disease
Sarcoidosis
Scar 8 ataxia (cerebellar)
Scheuermann disease
Scleroderma (systemic sclerosis)
SDHD
Sertoli-leydig cell tumors
Severe dry eye
Sickle cell anemia
Spina bi da and hydrocephalus
Spinocerebellar ataxia
Spinocerebellar ataxia 2
Spinocerebellar ataxia 3
Spinocerebellar ataxia 6
Spinocerebellar ataxia type 1: SCA1
Stiff person syndrome
Susac's syndrome
Suspected Brown-Violetto-Van Laere syndrome
Sweet’s Syndrome (Acute febrile neutrophilic
dermatosis)
Symphalangism familial proximal
Syringomyelia
Systemic vasculitis, mix of diseases
Takayasu’s arteritis
Takayasu’s vasculitis
Tarlov cyst disease
Thyroid eye disease
Transposition of the great arteries
Transverse myelitis
Trigeminal neuralgia
TSHOMA pituitary infarction, enlarged empty
sella, postural orthostatic tachycardia syndrome
Ulcerative colitis
Uncategorised vasculitis
Underactive thyroid
Undifferentiated connective disease
Unknown cause ataxia and cervical dystonia
Urticarial vasculitis
Vaginal cancer
Variegate porphyria
Vascular Ehlers-Danlos syndrome
Vasculitis
Vasculitis of the lungs
Vasculitis Wegener’s granulomatosis
Very long-chain acyl-coenzyme A dehydrogenase
de ciency
Wagner syndrome
WAGR/11p deletion
Waldenström’s macroglobulinemia
Warburg micro syndrome
Weaver syndrome
Wegener’s granulomatosis
Weil’s disease
Wilson’s disease
Worster-Drought syndrome
X-linked hypohidrotic ectodermal dysplasia
X-linked juvenile retinoschisis
X-linked periventricular heterotopia
Zellweger syndrome
30