Cardiac evaluation of myocardial involvement in Anderson–Fabry disease by cardiac magnetic resonance imaging: a study of five patients

Abstract

Abstract Background: Anderson–Fabry disease (AFD) is an X‐linked inborn error of glycosphingolipid metabolism due to a deficiency of the lysosomal hydrolase α‐galactosidase A associated with multisystemic involvement subsequent to deposition of neutral glycosphingolipid in many organs. Over time, microvascular disease of the kidneys, heart and brain progresses leading to premature death. Aim: To evaluate cardiac involvement in patients with AFD using gadolinium‐enhanced cardiovascular magnetic resonance imaging (MRI). Methods: We studied five patients (age range, 23–53 years two males and three females belonging to two different families) with a diagnosis of AFD made by low plasma α‐galactosidase activity and molecular analysis of mutations. Four of them had been treated with recombinant human α‐galactosidase A replacement therapy for at least 14 months. Clinical manifestations were assessed and an electrocardiogram and echocardiography (ECG) were performed in all patients for a preliminary evaluation of the cardiac involvement before initiating therapy. Coronary angiography and endomyocardial biopsy were performed in one patient. All patients finally underwent cine and late‐phase gadolinium‐enhanced cardiovascular MRI. Results: ECG and echocardiogram showed left ventricular hypertrophy in two patients and mitral insufficiency in three. Cine‐MRI confirmed these findings. Angiography showed the coronary artery to be free from lesions and histology revealed hypertrophic myocytes and the presence of fibrosis. Gadolinium‐enhanced MRI revealed hyperenhancement, mainly in the basal inferolateral wall, both in the subendocardial and mid‐wall layer, in the three older patients. Conclusion: These observations suggest that myocardial fibrosis occurs in Anderson–Fabry disease and may contribute to the hypertrophy and the natural history of the disease. The characteristic patterns of hyperenhancement differ from those seen in other myocardial pathologies (myocardial infarction, hypertrophic cardiomyopathy) and this may help in the differential diagnosis of the late‐onset forms (cardiac variant). Mitral valve insufficiency was also present in three patients, and this could be due to dysfunction of the inferolateral wall.