What Is Fabry Disease?

Are you familair with Fabry disease (FD) and it’s symptoms, especially for if you have been diagnosed with it? Fabry diseaseis a rare, inherited disorder that occurs when lipids and fats build up inside the body and are not broken down properly. Fabry disease can present in childhood or later in adulthood This disease can have many different implications and can affect a person’s day to day life significantly.

The purpose of this article is to help you gain awareness of Fabry disease, what causes the disease, the signs and symptoms, how Fabry disease is diagnosed and treated, and the different medication options that are available.

Overview

Fabry disease, also known as Anderson Fabry disease, is a rare disorder that is caused by a mutated gene on the X chromosome.¹ This gene is responsible for breaking down lipids in the body. When a mutation occurs, the lipids are not broken down and they build up inside the body.¹ This lipid build up can occur in different places such as the kidney, blood vessels, and heart.¹ Consequently, the disease can have many different disease manifestations. Fabry disease is passed down from parent to child via the X chromosome which is involved in sex determination.¹

There are 2 forms of Fabry disease. One is known as classic Fabry disease which develops during childhood or adolescence and the other form is late-onset Fabry disease which develops when individuals are in their 30s and above. Classic Fabry disease presents in 1 in 22,000 to 40,000 males and for females the number is unknown. Late-onset Fabry disease is seen in 1 in every 1,000 to 3,000 males and 1 in 6,000 to 40,000 females. Men are usually more severely affected by the disease than females.

Causes and genetics of fabry disease

Fabry disease is an inherited disorder which means that it is passed down from parent to child. The child inherits a mutated gene called alpha galactosidase A (GLA) gene which is found on the X chromosome.¹ The GLA gene codes for the production of the alpha galactosidase A (α-Gal A) enzyme which breaks down a fat called globotriaosylceramide. The mutation on the GLA gene causes less or no α-Gal A enzymes to be produced, so less lipids are broken down in the body.¹ Therefore, lipids build up inside the tissues and cells of the body, such as the kidney or heart and can lead to serious health implications.¹ 

Fabry disease is passed on through the X chromosome. Males have one  X and Y chromosome.. Females have two X chromosomes which they inherit one from their mother and one from their father. If the father or mother has Fabry disease, they will pass on the mutated X chromosome to their children. Females may have one mutated gene in each cell, which usually leads to less severe or no symptoms at all. If the mother has Fabry disease, there is a 50% chance that she will pass on her mutated X chromosome to their children.

Signs and symptoms of fabry disease

The signs and symptoms of Fabry disease can vary depending on if the person experiences classic or late-onset Fabry disease. If someone starts to get symptoms in their childhood or adolescence then they have classic Fabry disease. Late-onset Fabry disease is usually seen when someone is an adult. The signs and symptoms are more severe in classic Fabry disease. 

The main symptoms include:²

• Pain in the hands and feet which can get worse due to triggers such as fever, exercise, fatigue, and stress
• Burning, tingling, or prickling sensations in the hands or feet 
•  Little to no sweat production
• Reddish, purple spots/ skin rash usually near the hips or swimming trunk region known as angiokeratomas
• Gastrointestinal issues such as diarrhoea, constipation, cramps, stomach pain which may be particularly noticeable after a big meal
• Cloudy cornea, known as verticillata

Other symptoms of classic Fabry disease include chronic fatigue, weight gain, tinnitus, and hearing loss.² The symptoms mentioned above are usually only seen in classic Fabry disease and symptoms will differ from person to person.

Symptoms of Fabry disease can present later in life. Usually, 4 main areas of the body are affected including the renal, cerebrovascular, respiratory, and cardiac systems.² Different disease manifestations can appear in each of these organ systems and become progressively worse. Some of the implications are:²

• Renal (kidney) system
  • Kidney impairment, kidney disease, kidney failure, 
• Cerebrovascular system
  • Headache, dizziness, ischemic stroke, transient ischemic stroke
• Respiratory system
  • Shortness of breath during exercise, wheezing, chronic cough, obstructive airway disease
• Cardiac system
  • Arrhythmia, left ventricular hypertrophy, angina, heart attack, heart failure

Other symptoms of late-onset Fabry disease include hearing loss, tinnitus, dizziness, and depression.² The symptoms of late-onset Fabry disease overlap with other health conditions like multiple sclerosis, so it’s important to rule out possible causes. Additionally, if there is no other reason found for the complications, it may be a sign of Fabry disease in younger patients. It is important to speak to your doctor if you have any concerns surrounding Fabry disease.

Diagnosis and treatment of fabry disease

There are different diagnostic tests that can be used to diagnose Fabry disease. Diagnostic tests are usually performed if there are any symptoms, family history, or unexplained kidney, heart, or cerebrovascular complications (especially in younger patients) that suggests Fabry disease.³ Your doctor will discuss your symptoms with you to rule out other possible causes of pain. The diagnostic process used for males and females differ slightly. For males, an α-Gal A enzyme assay is used to check for activity levels of the α-Gal A enzyme.³ This is the enzyme which breaks down lipids in our body. If the enzyme activity is particularly low or there is no activity, this may imply Fabry disease. DNA sequencing is performed to find the GLA gene mutation that causes Fabry disease.³ In females only an GLA gene mutation screening is used  because the level of α-Gal A enzyme can be in the normal range and most of these females do develop Fabry disease, so the only reliable and accurate method of diagnosis is a GLA gene mutation screening.³

While there is no cure for Fabry disease there are treatment options available to help slow down the build up of lipids in the body. One of the treatment options used is enzyme replacement therapy.⁴ It works by using genetically modified α-Gal A enzyme that is underproduced in people with Fabry disease, so the fat in the body can be broken down. There are currently two different medications available agalsidase alpha or agalsidase beta.⁴ The medication is delivered to patients via an intravenous infusion every 2 weeks.⁴ Patients with classical or late onset Fabry disease can receive this treatment.

Another treatment option used is chaperone therapy.⁴ It helps to correct any faulty α-Gal A enzymes in the body, allowing the fat to be broken down and reduce build up in the blood vessels. The medication is called Migalastat and it is taken as a tablet.⁴ Chaperone therapy is only used for patients with a faulty α-Gal A enzyme folding mutation which means that not everyone with Fabry disease can take it.⁴ 

Standard treatments to treat heart and kidney problems are available to reduce the progression of life threatening complications. 

Management of fabry disease

Fabry disease can affect different organs in the body, your doctor may refer you for tests and examinations to check if any organs are affected and how severely they are affected. The doctor will then select an appropriate treatment regime depending on the results of these tests and examinations. 

They may check if the heart is affected by doing an electrocardiogram and an echocardiogram to check the heart’s rhythm and how well the heart is pumping blood around the body.² A doctor may do some urine tests to see how well your kidneys are working.² To check for any neurological involvement the doctor will carry out some neurologic tests and may perform a brain MRI if necessary.² The respiratory system and gastrointestinal system can also be affected, so your doctor may suggest some additional tests and examinations to check for any problems.² Additionally, they may recommend hearing and eye tests seeing as these areas can be affected by Fabry disease.² 

When to seek medical attention

If you are experiencing any symptoms or have any concerns relating to Fabry disease it is important to speak to your doctor. If you start to experience more serious symptoms or complications such as chest pain, shortness of breath, or signs of a heart attack then it is important to seek urgent medical help. 

Summary

Fabry disease is a lysosomal storage disorder which occurs when lipids or fats in the body aren’t broken down and they build up inside the body. It is caused by a mutation on the GLA gene which causes less or no α-Gal A enzymes to be produced on the X chromosome. These enzymes are responsible for breaking lipids and fats down. Fabry disease is a rare genetic disorder so it is passed down from parent to child. There are different symptoms associated with Fabry disease depending on when it presents. Classic Fabry disease occurs in childhood or adolescence and consists of symptoms such as pain in the hands or feet, reddish/purple spots , and gastrointestinal issues. Late-onset Fabry disease occurs in adulthood and affects different organs such as the heart or kidneys. Different treatment options are available for Fabry disease to help slow down the build up of fats in the body. If there are any concerns surrounding Fabry disease it is important to speak to a doctor.