Laboratory test/Genetics

Nowadays it’s not a big deal to get a genetic test. Nevertheless, if you suspect Fabry disease, you have to be aware of a few things. There are variants of the disease that are controversial in research (e.g. E66Q, F113C, R118C, A143T, N215S, D313Y; for further explanations see section: Variants/mutations). Therefore, here are some hints and tips for those who want to be tested for Fabry disease. Not every doctor can know what the expected consequences are for every change in every gene. Therefore it is  common for a gene laboratory to provide an assessment of a test result. Taken alone this may seem a welcome move. However, when it comes to testing for Fabry disease, certain studies may lead a lab to conclude that individual variants are harmless. For this laboratory, it can then be a justified procedure not to communicate these variants to the doctor at all. However, this approach is disadvantageous for those affected. These variants should be further explored, and to do so they must continue to be identified. When people with these variants have symptoms, doctors need to know about them. This is the only way to advance research.

Unfortunately, the so-called biomarkers such as measuring α-galactosidase A activity and determining the lyso-Gb3 level cannot provide unambiguous results either, since a gene defect can be present despite normal values. (See also Scientific Discussion) This also applies to men, since often only a test for the biomarkers is carried out.

That’s why we encourage anyone who wants to be tested for Fabry disease to:

Explain the above issues to your doctor and ask him to do a full sequencing of the GLA gene, including introns, asking the lab to also mention polymorphisms and benign variants in the test result. Men should insist on sequencing too!

Please also note that a “real” genetic test is carried out (sequencing) and not just a MLPA test or similar that is useless for this purpose (background information in our blog entry)

Unfortunately, if you test positive for the controversial mutations, it can be difficult to find a doctor who will treat Fabry disease. Nevertheless, a test result is important. Further research can only take place if these variants are further identified. In order to make doctors aware of the problem, testimonials from those affected are helpful. And it can also be good for your own peace of mind to know that you are not crazy, but really sick. Therefore: if you suspect Fabry disease, have yourself tested under the above conditions.

Hint:

At this this time we do not know any laboratry wich reports this controversial mutations. In some cases the doctor could ask laboratry for original results.

Obstacles at diagnosis

The consequence of the above-mentioned unauthorized assessment by at least one laboratory is that genetic tests carried out before a certain date are positive, and tests from the same people after this date are negative. This also means that those affected who had their family tested after a positive result sometimes received negative results from family members with similar symptoms, which led to great confusion.