This eBook has been developed by Idorsia Pharmaceuticals Ltd as a resource to support understanding of Fabry disease. It provides an overview of current knowledge about the condition, including how it develops, how it is diagnosed, and how it is managed.

Fabry disease is a systemic, progressive disorder that affects multiple organs throughout the body. While symptoms may vary between individuals, organ involvement, particularly of the kidneys, heart, and nervous system, plays a significant role in long-term disease outcomes.

This eBook highlights the impact Fabry disease can have on people living with the condition and those around them. It also outlines strategies that individuals and families can use, together with healthcare professionals, to manage Fabry disease as effectively as possible over time.

The eBook is intended for use by a general audience, including healthcare professionals seeking a clear and accessible overview of Fabry disease.
 

“My doctor called me up, had a chat with us as a family. I felt relief for my son, that at last we knew what was wrong. Then, sort of very scared, once we knew that everyone had got to go for health checks to find out who had got it and that it could cause lots of other problems with the major organs in your body. It was a scary time.”

Patient

Introduction

Fabry disease is a rare inherited disorder in which a particular lipid (a fat‑like substance) cannot be broken down properly by the body. As a result, this lipid gradually builds up in cells and tissues, leading to progressive damage in multiple organs.

Fabry disease is often undetected or misdiagnosed. Its symptoms can be nonspecific and may resemble those of more common conditions. Early symptoms such as pain in the hands and feet, rashes on the skin, and digestive problems, as well as more advanced symptoms over time such as kidney disease, heart disease or stroke could be caused by any number of diseases, which will usually have to be ruled out first. Because kidney involvement is a major determinant of long-term outcomes in Fabry disease, early identification and monitoring of kidney health is a cornerstone of effective disease management. 
 

Fabry disease is progressive, meaning that organ damage worsens as lipid accumulation continues. Importantly, organ involvement may begin long before obvious symptoms appear. This is particularly true for the heart and kidneys, where structural damage can develop silently over many years.

Early diagnosis is therefore essential. Identifying Fabry disease as soon as possible allows symptoms to be managed earlier, may help slow disease progression, and enables testing of other family members who might also be affected.
 

“I don’t have pain episodes like my children do. I have several children who have Fabry also, and the boys – three of my boys – have severe pain episodes.”

Patient

Understanding Fabry disease

What is Fabry disease and what causes it?

Fabry disease is one of nearly 50 conditions known as lysosomal storage disorders. These disorders affect a part of the cell called the lysosome, which is responsible for breaking down and recycling various substances, including lipids.

Fabry disease is caused by changes in the GLA gene, located on the X-chromosome. This gene provides instructions for producing an enzyme called alpha-galactosidase A (α-GalA). This enzyme plays a key role in breaking down a lipid known as globotriaosylceramide (Gb3).

When α‑GalA does not function properly, Gb3 cannot be broken down and begins to accumulate inside cells. Over time, this accumulation interferes with normal cellular function and leads to tissue and organ damage.

Accumulation of Gb3 occurs throughout the body but is particularly harmful in organs that rely on fine, specialized cellular structures, especially the kidneys, as well as the heart and nervous system.
 

How does Fabry disease affect the body?

In people with Fabry disease, Gb3 builds up inside cells lining blood vessels and within key organ tissues. This build‑up causes progressive damage, particularly in:

  1. Kidneys, where it affects filtering units and blood vessels
  2. Heart, where it contributes to thickening and scarring
  3. Nervous system and cerebrovascular system, where it interferes with pain signalling and blood flow, increasing the risk of stroke

Over time, this ongoing damage can result in serious complications such as chronic kidney disease, heart failure, and stroke. Because this process occurs gradually, organ damage may already be advanced by the time symptoms become apparent.
 

How is Fabry disease inherited?

The disease-causing GLA gene is located on the X-chromosome. Men have one X-chromosome, while women have two. Both men and women who carry the defective gene can develop Fabry disease, although symptoms are often more severe in men.

Women may experience a wide range of disease severity due to random inactivation of one X‑chromosome in each cell. As a result, some women may have few symptoms early on, despite having ongoing organ involvement.
Because Fabry disease is inherited, identifying one affected individual can lead to diagnosis in other family members. Family screening allows early monitoring of organ involvement, including heart health and kidney function, even before symptoms appear.
 

How common is Fabry disease and who gets it?

Fabry disease is a rare condition that can affect people of all ethnic backgrounds. Estimates suggest it affects fewer than 5 people per 100,000 in the general population. Both men and women can develop Fabry disease, and kidney involvement may occur across different disease types and levels of symptom severity.

Signs and symptoms of Fabry disease

The symptoms of Fabry disease vary widely and often change over time. Not all individuals experience the same symptoms, and some may develop organ damage before symptoms are noticeable, as previously mentioned.

“In high school, I remember having some episodes, I just didn’t get it. There was nothing wrong with me that anybody could see… I didn’t know what to do about it”

Patient

Diagnosis and treatment of Fabry disease

There are two typical routes leading to a diagnosis of Fabry disease: either the patient is the first person to be diagnosed in his/her family, or he/she has been tested because another family member has already been diagnosed.

While the diagnosis of a second family member is usually relatively fast and straightforward, as Fabry disease is already suspected and simple biological tests can prove or disprove the diagnosis, reaching a diagnosis for the first family member can be much more arduous.

Due to the low awareness of this rare disease and the non-specific nature of the symptoms that can be mistaken for other conditions, it often takes years of frustration and deteriorating health before a patient is referred to a specialist who can successfully diagnose Fabry disease.

What treatments are available for Fabry disease?

There is currently no cure for Fabry disease. However, treatments are available to help slow disease progression and manage symptoms.

Two disease‑specific approaches aim to reduce Gb3 accumulation:

  1. Enzyme replacement therapy (ERT), which replaces the missing enzyme
  2. Chaperone therapy, which enhances residual enzyme activity in some individuals

A key goal of treatment is to slow irreversible kidney damage, preserve kidney function, and help protect other organs, including the heart, supporting better long‑term outcomes. 

 

How kidney involvement may progress

Kidney damage in Fabry disease is progressive and may worsen over many years. Without treatment, kidney d amage can eventually lead to chronic kidney failure, when the kidneys are no longer able to function adequately. This progression is often reflected by gradually declining estimated glomerular filtration rate (eGFR) values. The speed of kidney function decline varies between individuals. Slower progression has been associated with factors such as earlier diagnosis, earlier treatment, lower levels of protein in the urine, and higher residual enzyme activity.

 

Progression of Fabry disease in other organs

In addition to kidney involvement, Fabry disease can cause progressive changes in other organs, particularly the heart and cerebrovascular system. Without treatment, the ongoing accumulation of Gb3 can cause progressive changes in the heart, including thickening of the heart muscle and scarring, which may affect heart function and increase the risk of complications. Changes in the blood vessels supplying the brain may also develop over time, increasing the risk of neurological events such as stroke or transient ischaemic attacks. The pattern and speed of progression varies between individuals and may be influenced by factors such as age, genetic variation, residual enzyme activity, and when treatment is started. Other symptoms affecting the skin, eyes, and nervous system may also contribute to the overall impact of Fabry disease.


 

“I’m a delivery driver. Sometimes the numbness in my hands makes delivering cases more difficult… I can still lift the cases and things like that, but small movements with my hands… sometimes it’s hard for me to control them.”

Patient

Burden of Fabry disease

Fabry disease places a substantial physical, emotional, and social burden on individuals and families. Progressive organ involvement can lead to end stage kidney disease requiring dialysis or transplantation, heart disease, and cerebrovascular complications such as stroke. These complications can significantly affect quality of life, employment, and family dynamics. Because organ damage is often cumulative and irreversible, early, and sustained management is essential.

Living with Fabry disease

Coming to terms with a diagnosis of Fabry disease can be challenging. Feelings of shock, anxiety, and uncertainty are common, particularly given the long‑term nature of the condition and the risk of organ complications. Support from healthcare professionals, patient organizations, and peer networks can help individuals and families navigate life with Fabry disease and maintain a positive outlook.
 

Fabry disease can impact a child or young adult’s education, with time off needed for regular hospital appointments or due to illness. Physical activities such as sports at school can be more difficult for children with Fabry disease to take part in because of the pain and tiredness caused by the disease. As a result, children and young adults with Fabry disease can become isolated from their peers, being seen as less able to ‘keep up’ with their friends or excluded for being ‘different’.

It can be helpful for parents or young adults to meeting with the school or university ahead of the academic year to discuss any practical needs in advance, such as timetabling around hospital appointments, addressing physical education classes and how to explain the condition to other students.

“You try to stay positive... but it’s very emotional and it drains you.”

Patient

Understanding the management of Fabry disease

Fabry disease is typically managed through long-term monitoring and care, as the condition can affect multiple organs over time. While symptoms such as pain or fatigue may be noticeable early on, organ involvement can progress silently, especially in the heart and kidneys. For this reason, people with Fabry disease are often monitored regularly by their healthcare team, even if they are feeling well.

The kidneys play a key role in Fabry disease outcomes. Kidney function is often normal during childhood, but the gradual build‑up of Gb3 can cause progressive kidney damage over many years. Monitoring kidney function is relevant from childhood through adulthood, even when tests are normal. Early identification of kidney involvement and timely treatment may help slow disease progression, reduce complications, and preserve kidney function for as long as possible. 

 

Living with Fabry disease and kidney involvement

Regular follow‑up with a kidney specialist is an important part of Fabry disease care. Monitoring schedules vary depending on disease severity but often include blood and urine tests every few months, alongside monitoring of other organs, including the heart, as recommended by their healthcare team. People living with Fabry disease are encouraged to discuss kidney health openly with their healthcare team and to follow recommended lifestyle measures, such as staying hydrated, taking medications as prescribed, remaining physically active, and avoiding smoking, to support long‑term kidney health.
 

 


 

Reaching out for support

Some people find support group meetings or online forums very valuable, allowing them to speak with and learn from other people who are going through similar experiences. The level of support for families affected by Fabry disease varies greatly from country to country. Local associations and healthcare professionals can often be a good source of information about benefits, grants, social services and other resources available. In addition to care from a specialist, people with Fabry disease may also benefit from being referred to other multidisciplinary team members, including psychologists, to offer emotional counsel.

It is normal to feel shock and grief after being diagnosed with a progressive, life-long disease, but it is important to know that people with Fabry disease can still lead rewarding, happy lives.

                  

While there may be things that are more difficult to do or achieve with Fabry disease, setting realistic goals and focusing on what is still possible can make it easier to maintain a positive outlook. Talking to other families affected by Fabry disease can often be helpful for coming up with ways of adjusting to a new reality and coping with the challenges that the disease may present.

There are many patient associations dedicated to supporting patients and their families to live well with Fabry disease by providing detailed information and practical advice.

A list of organizations around the world can be found on the Fabry International Network website at fabrynetwork.org/fin-members.

This resource has been developed by Idorsia Pharmaceuticals Ltd in order to provide an environment to deliver a better understanding of Fabry disease and to pool information regarding the disease, the diagnosis procedure, available treatments and the impact it could have on the life of someone diagnosed with Fabry disease. The resource is for use by a general audience.

The information in this resource is not intended as a substitute for advice/treatment by a physician, whose instructions should always be followed. Neither does the information provided constitute an alternative to advice from a doctor or a pharmacist and should not be used on its own to produce a diagnosis or to commence or cease a particular treatment.

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