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Testing & Diagnosis

How is Fabry disease diagnosed?

Recognising that someone has Fabry disease can sometimes be hard because its symptoms are often confused for other common diseases. For example stomach cramps or diarrhea may be thought to be irritable bowel syndrome. An affected person may at first be misdiagnosed and in fact may have symptoms for many years without knowing they have Fabry disease.

Males can be diagnosed through a blood test that measures the amount of alpha-GAL in the blood. A female who has Fabry disease may have normal levels of alpha-GAL in the blood, and needs genetic testing to determine whether or not they have the disorder. Genetic testing looks at a person’s DNA to see if they carry the Fabry mutation.
The  enzymatic identication of females is less reliable due to the random X-chromosome inactivation in women. Daughters of classically-affected males may have enzyme activity ranging from normal to very low. Thus, in females, only the identication of an GAL A mutation in the GLA gene provides completely accurate identication. It is important to determine the mutation status in all at-risk females in families with Fabry disease, including those who are currently asymptomatic.

Subtypes of Fabry disease and their presentation

Complete absence of, or less than 1% of normal levels of, GAL A enzyme results in the “classic” subtype of Fabry disease. Classic Fabry disease typically has an early onset, which can occur in childhood or adolescence.

Commonly, the earliest signs and symptoms of classic Fabry disease can include:

  • Episodic excruciating pain and burning sensations in the hands and feet which are often provoked by physical exercise, fatigue, fever, stress, heat exposure, or change in weather conditions; such episodes are called Fabry's crises, and may persist for hours or days; pain may also be present in the arms or legs;
  • Sharp pain which can occur anywhere in the body;
  • Gastrointestinal problems, including abdominal pain and cramping, diarrhea, bloating, nausea, and inability to gain weight;
  • Raised or at, dark-red, purplish or blue-black benign skin papules (angiokeratomas), the majority of which occur between the umbilicus and the knees;
  • Inability to perspire adequately or to perspire at all (anhydrosis), which results in overheating during physical activity, with resulting discomfort and fevers;
  • Corneal clouding (corneal dystrophy) that does not affect vision; and
  • Delayed puberty or delayed growth. 

Affected individuals whose -GAL A enzyme is present at greater than 1% of normal levels have the more-or-less attenuated, later-onset subtype of Fabry disease. They usually do not experience the classic-subtype early symptoms listed above. Rather, symptoms of kidney, heart or cerebrovascular involvement usually occur between the ages of 30 to 45. It is the first appearance of such kidney, heart or cerebrovascular symptoms that often leads to the initial diagnosis of late-onset Fabry disease. Males and affected females with late-onset Fabry disease may experience any of the following symptoms or complications. Individuals with the classic-subtype of Fabry disease, as they age, may also add any of the following symptoms or complications to their early symptoms noted above:

  • Severe kidney problems resulting in renal insufficiency and ultimately, end-stage renal failure;
  • Myocardial ischemia and infarction;
  • Transient ischemic attacks;
  • Stroke
  • Cardiac arrhythmia;
  • Hypertension;
  • Cardiomegaly;
  • Left ventricular hypertrophy;
  • Hypertrophic cardiomyopathy;
  • Cardiac failure;
  • Mitral valve prolapse or insuciency;
  • Lymphedema in the feet and legs;
  • Hearing loss which can be progressive, and possible sudden deafness;
  • Frequent bowel movements after eating;
  • Joint or back pain;
  • Tinnitus and/or vertigo;
  • Headache;
  • Generalized weakness;
  • Nausea and/or vomiting;
  • Chronic bronchitis or shortness of breath.

As implied by these complications, patients with Fabry disease suffer from complications from strokes, heart disease, or renal failure.

Source; Indications, Newsletter of the Lysosomal Disease Network, February 2014

Following a positive diagnosis of Fabry disease 

A diagnosis often comes with mixed emotions ranging from a huge sense of relief from the worry, anxiety and frustration associated with searching for a diagnosis for yourself, your child or family member to feelings of being overwhelmed not knowing much about Fabry disease and the impact on other members within your immediate and extended family. You are not alone and Fabry Australia provides mutual support sharing experiences and information on living with Fabry Disease.

You may have many questions when first diagnosed with Fabry disease ranging from; who discovered Fabry disease?; What is the incidence?; What are the symptoms?; Are there treatments?; How is the disease managed?; What impact will it have on my life? What research is being done in Australia? 

The Fabry Australia website is a good place to start reading, exploring and receiving answers to some of your questions. You can also write down your questions and phone Fabry Australia or take them to your next Fabry clinic appointment. The Fabry clinicians and staff are only too happy to help and answer any questions you may have.

Having a diagnosis is very useful for Doctors in start symptom management, reducing the risk of further problems happening as well as early identification of other family members who may be affected. Initially, a combination of the signs and symptoms may lead your doctor to think you may have Fabry disease. 

Fabry disease Testing

Anyone who is thought to have Fabry disease can have the diagnosis confirmed through laboratory testing. This test, called an enzyme assay measures the amount of a-galactosidase enzyme activity in the blood. 

In males this can be done by taking a blood sample which is then tested to check the level of the a-galactosidase enzyme. If the level of the enzyme is very low a diagnosis of Fabry disease can be made. This test can also be used to confirm the diagnosis of Fabry disease in females, although a laboratory genetic test in which DNA is analysed is a more effective test for confirming the diagnosis in women especially where there is a family history of Fabry disease.

Prenatal diagnosis is possible by measuring the a-galactosidase activity in tissue or fluid taken from around the foetus. This test may be offered to expectant mothers who have Fabry disease. Specialist support and advice are available for such testing.

Family Testing

If you or a family member has been diagnosed, others in your immediate and extended family may also have Fabry disease. Fabry Disease is a genetic inherited condition and can affect more than one person in the family. It is important to speak with your family members about your diagnosis and encourage them to be tested. The tests which measure alpha-galactosidase enzyme activity, lyso-ceramide trihexoside and for known familial mutation testing can be ordered using a pthology referal form by your Doctor. It is also very helpful and advisable to consider Genetic Counselling when family planning or first diagnosed to understand the inheritance pattern of Fabry Disease. There are Genetic Counsellors throughout the country and the Fabry Clinics can refer you to a Genetic Counsellor to support you and your family with your new diagnosis.

Fabry Australia has an 'Understanding Fabry Disease' Fact Sheet booklet to help talk with your family about Fabry Disease.

Testing Costs 

Any clinician can order tests to diagnose Fabry Disease. If the test is completed within the Fabry Clinic setting there is no cost to the patient. If the test is ordered privately there are costs associated with the test. Fabry Clinics have access to two Dry Blood Spot testing kits which have been provided by two pharmaceutical companies. One test is completed within Australia and the other is sent to Germany. Both are free to the Fabry Clinician and to the patient. To understand more about these tests please direct your questions to your State Fabry Clinic. If you have a clinician outside of the clinic looking to conduct a test, please refer them to the Fabry Clinic for further information.