Fabry support group (MFSH) at the FIN meeting in Amsterdam on D313Y

Natascha and Berthold from MFSH were at FIN meetings in Amsterdam. FIN=Fabry International Network, an association of Fabry self-help groups from all over the world.

The presentation of the research work on “controversial variants” or D313Y was the highlight. The work could be presented to patients and scientists from all over the world.

The presentation and patient stories shown in Amsterdam can be downloaded from MFSH.

Info about GLA gene testing in Fabry disease in Germany

IMPORTANT for all who have been genetically tested for Fabry disease in the last years!
The laboratory findings may be incomplete and it could be that a variant is present but not reported.

Only pathogenic/disease causing variants are still reported in the findings!

The arbitrary classification of variants as benign/ benign by the laboratories means that they are no longer reported. The report only states:

NEGATIVE FINDING
No clinically relevant variant was detected or
No pathogenic variant found

It is not possible to determine an exact date for this procedure, as some laboratories were already practicing this before the GEKO decision. Here, the tests offered free of charge by the pharmaceutical industry stood out in a particularly negative way.

Background:
The German Genetic Diagnostics Commission has decided that laboratories should only report disease-causing and probably disease-causing variants in their findings. Variants of unclear significance may be mentioned in the findings. Benign and probably benign variants should no longer be reported.


There are five classifications regarding the pathogenicity of mutations/variants:

  • pathogenic- pathogenic (causing disease)
  • likely pathogenic- probably pathogenic (causing disease)
  • uncertain significance
  • likely benign – probably benign
  • benign- benign

More info at:
https://a143t.org/labortest-genetik/
https://a143t.org/gentest-was-und-wie-wird-eigentlich-getestet/

Untreated patients are driven to suicide

In Germany, the controversy over the “controversial” variants of Fabry disease (a multi-organ disorder) has escalated further. Once again, some patients have had their therapy withdrawn. They had been in treatment for many years and felt a marked improvement in their symptoms. The focus was on devastating pain that could not be managed with standard pain therapy. Children also stopped treatment, although they clearly benefited from it. One child has been treated since the age of 4 and over a period of 7 years. Another child is now about to graduate from high school. Patients whose genetic defect was diagnosed in a stroke are also affected.

The first patients whose treatment was discontinued are already showing worsening symptoms. They are now in despair because they have experienced that the therapy has significantly improved their symptoms and because they now see no possibility of continuing to receive therapy. Parents are faced with the insurmountable task of explaining to their children why they are no longer receiving therapy.

Many of those affected can no longer imagine a life without the therapy and express this clearly. Some have already joined an euthanasia organization.

Patients who are still receiving therapy live with the constant fear that their therapy will also be terminated and have to helplessly watch others being taken off therapy or not receiving it at all.

The fact that these “controversial” variants do not make people ill is repeatedly claimed by various scientists, and there is also talk of a placebo effect. However, there are also other scientists who have proven a pathogenic effect of the variants. Because the experts are not in agreement, the discussion is now being carried out on the backs of the patients.

There is no question that the therapy helps, the drugs have a targeted effect only on Fabry, there is no known random effect in other diseases.

The claim that these “controversial” GLA gene variants do not cause Fabry is simply wrong! On the other hand, we can prove all our statements.

Fabry as a lysosomal storage disease, is there possibly more to it?

Yes, at least in a certain proportion of patients.

There is always talk of an enzyme deficiency that leads to deposits in the cells and then triggers the malfunctions. In many missense variants (i.e. an amino acid is altered somewhere in the DNA on the GLA gene) there is a residual activity of the enzyme. Nevertheless, the patients are often also severely affected. Here, another mechanism comes into play: ER stress or Unfolded Protein Response (UPR).

A brief explanation: Due to the variant, the enzyme is formed, but it is partly defective. Now a kind of “quality assurance” kicks in in the cell. The faulty enzyme is “repaired”. This is a normal process in the cells, since minor errors can happen again and again. However, due to the variant, the enzyme is permanently formed incorrectly and the error correction is overloaded. This is ER stress, which can lead to malfunctions of a cell or even cause cell death.
Caperone therapy also “repairs” the wrong enzyme and relieves the cell. Here, enzyme replacement therapy would be less effective.

This mechanism has been demonstrated for some time, including for some of the controversial variants. But this explanation is not accepted by all scientists because it contradicts their own publications.

We patients are the ones who suffer; we are then prescribed no therapy or a less effective one.