A 48 year old man presented with a bifascicular block at a routine check-up. He did not complain for exertional dyspnoe or angina nor for syncopes or dizziness. Cardiac risk factors were not known, especially he had no arterial hypertension. There was no abnormality in the clinical examination. CK was elevated with 263 U/l (normal <171), Troponin I with 0,36 μg/l (<0,05). The echocardiogram revealed a dilated left ventricle (58 mm, Henry-index 120%) with a normal ejection fraction. He had a considerable left ventricular hypertrophy (diastolic septal wall thickness max. 19 mm). In an exercise test he could perform 150 W, the ECG showed several couplets.
The diagnosis of a Fabry disease, which was suspected after immunohistochemical investigation of the biopsy was confirmed by the enzyme test with an alpha-galactosidase activity reduced to 0,05 mmol/min/mg (normal 0,4-1,0). Genetic testing confirmed a transition C644A>G (N215S). Renal function as well as the findings of the opthalmologist and neurologist was normal. A family pedigree was drawn, no abnormalities were reported.
What would be the next steps concerning the patient and his family?
The diagnosis of Fabry disease was explained to the patient, and an enzyme replacement therapy was offered. This has started in the meantime and is well tolerated by the patient.
We offered enzyme testing and consulting to the family. Several family members were newly diagnosed as carriers of the same mutation (fig.2).
In otherwise unexplained cases cardiac hypertrophy might be the result of a storage disease. A careful clinical examination and history taking might give hints for a special form of disease, otherwise an endomyocardial biopsy can show typical alterations.
Fabry disease is a rare lysosomal storage disease caused by a deficiency of -galactosidase A, which results in progressive accumulation of globotriaosylceramid in different organs, leading e.g. to renal failure, neurovascular symptoms and neuropathic pain, gastrointestinal complaints, angiokeratomas and corneal dystrophy. Cardiac involvement commonly includes cardiomyopathy and rhythm disturbances
(e.g. bradyarrhythmia, AV-block, bundle branch block, ventricular tachycardias), rarely arterial disease and valvular disorders. Heart disease in Morbus Fabry might be the fatal complication.
Some years ago enzyme replacement therapy (ERT) was approved for the treatment of the disease. Several small clinical trials and observational studies show positive effects e.g. on renal function and cardiac mass whereas great randomised end-point studies are still on the way. In the meantime we have to carefully follow both patients and their asymptomatic relatives to find the optimal time to start ERT.
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