Fabry disease – it’s worth taking a closer look

02.12.2015 12:27

An early diagnosis is important for Fabry disease: “Only an early start to therapy can stop the progression of the disease and prevent irreversible consequential damage,” emphasized Prof. Dr. Max J. Hilz, Erlangen, at a symposium as part of this year's congress of the German Society for Neurology (DGN). The "FabryScan", a diagnostic instrument specially developed for neurology, can help doctors make an earlier diagnosis.

In Fabry disease, due to a genetic deficiency of the lysosomal enzyme α-galactosidase A (αGalA), the metabolite globotriaosylceramide (GL-3) accumulates in the lysosomes of body cells, especially in the vascular endothelial, kidney and cardiac muscle cells as well as in Neurons. In the early stages, symptoms such as neuropathic pain, hypohidrosis and angiokeratomas occur. As the disease progresses, multiple organ damage and complications such as kidney failure, heart failure or strokes can occur. Since numerous mutations of the αGalA gene are known, which can lead to reduced activity or even a complete absence of αGalA, the clinical picture and the course of the disease are correspondingly diverse.

“One of the first symptoms of Fabry disease is the very early damage, especially to the thin-caliber nerve fibers. If children have spontaneous burning pain in their hands and feet and if they also feel uncomfortable in hot ambient temperatures or develop pain if the pain increases during sporting activities, then you definitely have to think about Fabry disease,” advises Hilz

“FabryScan”*: a diagnostic tool for early detection

The Kiel Prof. Dr. Ralf Baron and his team developed the “FabryScan” specifically for the differential diagnosis of patients with unclear extremity pain and to differentiate from, for example, growing pains, (juvenile) rheumatism and unclear polyneuropathies. A score can be calculated using a questionnaire based on ten questions and three simple bedside tests to determine mechanical and cold sensations. Its level provides information about the likelihood of a patient suffering from Fabry disease. The test was validated in a multicenter study in 143 pain patients with Fabry disease, rheumatoid arthritis or polyneuropathy. The test is characterized by a high sensitivity of 88 percent and a specificity of 87 percent.

As part of a joint initiative with Genzyme, the “FabryScan” has been used in 502 neurological practices across Germany since January 2015. “The initiative is very well accepted in practice; we have already received almost 100 completed forms and have already identified four Fabry patients (as of September 2015),” says Baron happily.

The diagnosis is finally confirmed using a dried blood test, in which the residual αGalA enzyme activity is determined. For women, additional genetic testing is always necessary because the enzyme level in women can be relatively normal, added Hilz

Early start of therapy is important

To treat Fabry disease, causal therapy is available using enzyme replacement therapy (EET), e.g. B. with Agalsidase beta (“Fabrazyme”), the recombinant form of human αGalA. The recommended dosage is 1mg/kg/KG every two weeks as an intravenous infusion.

Hilz advocated for an early start to therapy because “if you start therapy early, it is possible to destore the GL-3 deposits in the heart, kidney and nerve cells and you can stop the progression of organ damage or, in the best case scenario even prevent it.”