Cardiomegaly of Unknown Origin: Why Morphology Still Matters in the Genetic Era - A Case of Cardiac Fabry Disease.

Abstract

We report a 72-year-old man with long-standing hypertension, type 2 diabetes, and ischemic heart disease, in whom autopsy, following a fatal acute coronary syndrome, revealed marked cardiomegaly (heart weight, 911 g) and concentric myocardial hypertrophy (left ventricular wall thickness up to 2.4 cm) that appeared disproportionate to the expected degree of hypertensive and ischemic remodeling. Histological examination showed diffuse vacuolization of cardiomyocytes with a negative periodic acid-Schiff reaction; amyloidosis and glycogen storage diseases were excluded. Electron microscopy, α-galactosidase A activity, lyso-globotriaosylceramide measurement, and genetic testing were not available. Sudan III staining of frozen myocardial sections demonstrated intracellular lipid inclusions, providing supportive but non-specific evidence of a suspected non-classical (cardiac) variant of Fabry's disease. This case highlights the importance of careful morphological evaluation in the differential diagnosis of unexplained severe left ventricular hypertrophy and illustrates both the diagnostic utility and the limitations of conventional histopathological methods in autopsy practice.