Intense myocardial uptake in a patient with fabry disease—a new cause of false positive of bone scintigraphy mimicking cardiac amyloidosis

Bone scintigraphy has emerged as a key diagnostic tool for transthyretin cardiac amyloidosis (TTR-CA). Despite its high sensitivity and specificity, false positives can occur, causing diagnostic challenges. A 61-year-old male presented with syncope and left ventricular hypertrophy (LVH) and underwent cardioverter-defibrillator implantation. Genetic testing with a 72-gene panel revealed a pathogenic (class 5) variant in the GLA gene: p.(Asn215Ser). He was referred to our cardiomyopathy centre for management of his Fabry disease. Transthoracic echocardiography showed marked diffuse and symmetrical LVH (Panels A and B) (maximal wall thickness = 25 mm), low-normal ejection fraction (55%), and impaired global longitudinal strain (Panel C). α-galactosidase A activity was 1.8 µmol/L/h (normal value > 2.8). Migalastat therapy was initiated. A few months later, the patient underwent bone scintigraphy with 99mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) coupled with CT imaging for a rheumatologic indication, revealing intense myocardial uptake (Perugini 3), suggestive of TTR-CA (Panel D). However, repeated genetic testing excluded TTR mutations, and haematologic screening for AL amyloidosis was negative. No known confounding factor associated with false positive bone scintigraphy such as hydroxychloroquine use, recent myocardial infarction, or recent intravenous iron administration was observed. An endomyocardial biopsy found no amyloid deposits but a characteristic vacuolization of cardiomyocytes, confirming Fabry disease-related cardiomyopathy (Panel E).