Kardiomyopathie bei Morbus Fabry

Fabry disease – a rare but important cause of left ventricular hypertrophy. Fabry disease (synonym: Morbus Fabry, Anderson Fabry disease) is an Xlinked lysosomal storage disease due to a deficient activity of alpha-galactosidase A. This leads to pathological glycosphingolipid metabolism, resulting in deposition of glycosphingolipids in lysosomes and body fluids. There is evidence that the glycolipids also accumulate extralysosomally, which is a very important factor in the pathogenic impact. Cardiac involvement is one of the most important disease manifestations because the patients mainly die from cardiac complications. There are two phenotypes: classic and later-onset. First symptoms of the classic phenotype occur during the childhood and include angiokeratomas, hypohidrosis, cornea verticillata, and tortuosity of conjunctival and retinal vessels. Young patients typically suffer from acroparaesthesias, abdominal cramping and pain crises. With advancing age, the progressive sphingolipid deposition, particularly in the endothelial cells, cardiomyocytes and podocytes, leads to arterial hypertension, cardiomyopathy, nephropathy and premature strokes. In contrast to the classic phenotype, patients with the later-onset phenotype lack the early disease symptoms. They typically present to the hospital in adulthood with cardiomyopathy or with nephropathy. In females, alpha-galactosidase A activity can range from low to normal owing to random X-chromosome inactivation. Generally, females have a milder phenotype because of the second, unaffected X-chromosome. Patients with Fabry cardiomyopathy suffer from left ventricular hypertrophy, conduction abnormalities and valvular involvement, as well as from diastolic and/or systolic heart failure symptoms. The enzyme activity determination in leucocytes is diagnostic in males but can be misleading in females owing to random X-chromosome deactivation. Thus, genetic testing is suitable for the diagnosis in females and should also be performed in males for the confirmation of the diagnosis. Since 2001, intravenous enzyme replacement therapy has been available for the treatment of patients with Fabry disease. Since 2016, oral pharmacological chaperone therapy has been available for patients with amenable mutations. Substrate reduction and gene therapies are currently in development.