Fabry disease: how to live a normal life with a rare disease

What is Fabry disease? 

A rare genetic condition linked to chromosome X 

Fabry disease is an inherited disorder linked to a mutation in the GLA gene on the X chromosome. This mutation prevents the production or proper functioning of an essential enzyme: alpha-galactosidase A. As this gene is carried on the X chromosome, the disease affects men and women differently. Men, who have only one X chromosome, generally have more severe forms of the disease. Women may be asymptomatic, have few symptoms, or develop severe forms the disease. There are two main forms of the disease: the classic form, with symptoms appearing in childhood or adolescence, and the milder form which develops later in life.

Deficiency of the alpha-galactosidase A enzyme

In patients with Fabry disease, the alpha-galactosidase A enzyme is absent or malfunctioning. The enzyme deficiency leads to the accumulation of the enzyme's glycosphingolipid substrates, essentially Gb3 (globotriaosylceramide) and its deacylated derivative, lyso-Gb3 or globotriaosylsphingosine.

In the absence of the enzyme, these substances gradually accumulate in the cells, particularly those of the kidneys, heart, nervous system and skin. This accumulation provokes the symptoms and complications of the disease.

What are the symptoms of Fabry disease? 

Early symptoms 

The first signs of Fabry disease generally appear in childhood or adolescence. Neuropathic pain, or acroparesthesia, is a common symptom which manifests itself by burning, tingling or electric discharge sensations in the hands and feet. Angiokeratomas, small red or purple skin lesions, are a also typical sign. Other early symptoms include reduced or absent sweating (hypohidrosis), heat intolerance and gastrointestinal problems (abdominal pain, diarrhoea).

Gradual organ damage 

Over time, the symptoms become worse. 

The progressive accumulation of Gb3 in the kidneys eventually impairs their function, leading to kidney failure. The presence of protein in the urine is the first sign of kidney damage, easily detected by a urine test. Gb3 disrupts the kidneys' filtering role, which may eventually lead to the necessity of dialysis or kidney transplant.

In addition, the presence of Gb3 in the heart leads to thickening of the heart walls and various circulatory disorders, such as high blood pressure, mitral valve prolapse, cardiac hypertrophy, heart attacks, heart failure, arrhythmia and strokes. The first signs of these conditions are often an accelerated or irregular heartbeat. The risk of cardiac complications increases with age.

The nervous system can also be affected, causing dizziness, headaches, hearing loss or tinnitus.

Finally, the cornea may reveal a specific appearance known as ‘whorled cornea’, identifiable during an eye examination. 

Differences between men and women 

In men, symptoms often appear earlier and are more severe. In women, there is considerable variability of cases: some may present with clinical manifestations similar to those of men, while others have few or no symptoms. This variability is due to the random inactivation of one of the two X chromosomes.

How is Fabry disease diagnosed? 

Clinical examination 

The diagnosis is often based on a number of clinical factors: atypical pain, family history of early kidney or heart disease, the presence of angiokeratomas, hearing or eye problems. It is essential for healthcare professionals to be aware of Fabry disease so that the correct diagnosis can be rapidly established.

Additional tests 

Diagnosis of Fabry disease is based on a blood test to measure the activity of the alpha-galactosidase A enzyme. In men, an abnormally low level or non-existence of the enzyme generally confirms the diagnosis. However, in women, due to the random inactivation of one of the two X chromosomes, the enzyme activity may remain normal in around 40% of cases. This is why a genetic analysis is often necessary to detect a mutation in the GLA gene, responsible for the production of this enzyme.

Genetic testing 

Once a patient has been diagnosed, screening is offered to family members. This enables carriers of the mutation to be identified at an early stage and appropriate monitoring or treatment to be put in place.

How can the disease be treated? 

Specific therapies

Two specific types of treatment are available. Enzyme replacement therapy involves regular intravenous administration of a recombinant form of the alpha-galactosidase A enzyme. This treatment aims to reduce the accumulation of Gb3 (globotriaosylceramide). Another option is a medication that stabilises the mutated enzyme when it is still partially functional. However, this oral treatment is only effective in some patients, depending on the type of mutation.

Multidisciplinary care 

The complexity of Fabry disease requires coordinated, multidisciplinary care. Patients are often monitored in specialist centres, which bring together nephrologists, cardiologists, neurologists, ophthalmologists, dermatologists and geneticists. The aim is to provide a comprehensive follow-up care tailored to the progression of the disease.

Symptomatic treatments 

In addition to major background treatments, care includes treating the symptoms of Fabry disease: painkillers, treatment of digestive problems, hearing aids if necessary, etc. In the event of serious complications, such as end-stage renal failure, dialysis or a kidney transplant may be considered.

Living with Fabry disease 

Regular monitoring and everyday adjustments 

Fabry disease requires rigorous medical monitoring throughout life. It is important to adjust certain daily activities according to the symptoms: avoid extreme heat in the event of hypohidrosis, do moderate-intensity, appropriate physical exercise, and have a well-balanced diet to protect the target organs.

Psychological impact

Managing a rare, chronic and often invisible disease can have a significant psychological impact. Anxiety, chronic fatigue and the feeling of isolation are common. Psychological support can be extremely useful for patients and their families.

Getting help 

Patient support groups such as Metabolic Support offer information, support and assistance. They help to break down isolation, provide access to reliable resources and give people a better understanding of the issues surrounding the disease. Online discussion groups, such as Carenity, can also provide support for patients and their families.

What you need to know about Fabry disease 

Fabry disease is a rare and serious genetic disorder that affects several organs and causes symptoms that vary greatly from one person to another. It is caused by a deficiency in the alpha-galactosidase A enzyme, which is responsible for the accumulation of toxic substances in the body. Diagnosis is based on a range of clinical, biological and genetic factors. Treatments now exist to slow down the progression of the disease and alleviate its symptoms. Regular monitoring, multidisciplinary care and overall support are essential to improve patients' quality of life. Knowing more about Fabry disease also means earlier diagnosis and a brighter future for patients and their families.

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