4.3. Confirming a diagnosis


Fabry Disease is a fairly rare disorder. The classical form of Fabry Disease, which is what you’re worried about in children is only about one in every 40,000, but it does tend to cluster so if you have one family you’re likely to have more than one patient.

Once considering Fabry Disease, how do you confirm the diagnosis? There is a little bit of a difference between boys and girls, because this is an X-linked disorder, however it’s an X-linked disorder that affects both males and females, so you want to pay attention to the girls, but the way that you confirm the diagnosis is the same.

For a boy where you need to know ‘is there Fabry Disease?’, the standard test has typically been to measure the enzyme activity, and that can be done through a number of labs. Pediatricians can ask a lab that does biochemical genetic testing for that testing to be done. Boys can also be tested by sequencing the gene, the a gal gene and doing molecular studies for Fabry Disease. If they find a mutation that has been associated with disease or that would lead to an incomplete protein then you have a diagnosis. If they do not find a mutation and there’s a family history of Fabry Disease then they can ask if anybody in the family has had testing. If they have and it was identifiable with a standard molecular testing then that child probably doesn’t have Fabry Disease. If the family mutation isn’t known or if the child is being evaluated based on symptoms, in a male child they would then need to do enzyme activity to be sure that the child didn’t have Fabry Disease. Occasionally boys with Fabry Disease will be identified because they required a kidney biopsy, a heart biopsy or a skin biopsy and found the typical inclusions. We confirm the diagnosis at that point with either the molecular study or the enzyme acid.

For girls, because it’s an X-linked disorder they have two copies of the gene, and with random enzyme activation they will have some cells that produce the enzyme and some that do not. That does not keep females from having the disease but it does make it so that the enzyme test as a blood test is not reliable.  Generally speaking in order to rule out Fabry Disease in a girl one needs to do a molecular test. If for some reason this cannot be done, although that would be really exceptional circumstance, a kidney biopsy or heart biopsy could be substituted. Most patients prefer the molecular testing, which is a simple blood test.





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