Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase α (GLA) gene, leading to a deficiency in or absence of α-galactosidase A activity. The resulting accumulation of globotriaosylceramides affects multiple organs, with a particular predilection for the cardiovascular system, manifesting as left ventricular hypertrophy (LVH), arrhythmias, and heart failure.

Despite the increasing awareness of FD’s natural history, diagnosis is often delayed—particularly in the cases with nonspecific clinical presentation or absence of overt symptoms. In such scenarios, organ involvement may only be detected through advanced, targeted diagnostic modalities.

A 55-year-old woman with no history of chronic illness was admitted to be qualified for a dedicated FD therapeutic program. A diagnosis of the GLA gene mutation (c.126G>C) was established through family cascade screening. She reported gradual vision deterioration since the age of 40 years and intolerance to cold, manifesting as burning pain in the extremities. On admission, she had no cardiovascular symptoms. Laboratory tests showed elevated levels of N-terminal pro–B-type natriuretic peptide (383 pg/ml; reference rage [RR] <⁠125 pg/ml) and high-sensitivity troponin T (39 ng/l; RR <⁠14 ng/l), with normal creatine kinase (55 U/l; RR, 0–190 U/l) and creatine kinase myocardial band (13 U/l; RR, 0–24 U/l) results. Moreover, dyslipidemia (total cholesterol, 6.35 mmol/l; RR, 3–5 mmol/l) and proteinuria (proteins, 19.7 mg/dl; RR <⁠12 mg/dl) were found.

Transthoracic echocardiography demonstrated concentric LVH with LV outflow tract obstruction (LVOTO). The resting gradient was 52 mm Hg, without augmentation during Valsalva provocation. LV dimensions, systolic function, global and regional wall motion, as well as valvular structure and function were within normal limits. The myocardium showed a granular texture, particularly in the interventricular septum (Figure 1A–1D). Twenty-four-hour Holter electrocardiography recorded a sinus rhythm with a mean ventricular rate of 83 bpm (range, 58–126 bpm), with no significant arrhythmias or conduction abnormalities.

Figure 1. Echocardiography of a patient with Fabry disease; A – parasternal long-axis view showing concentric left ventricular hypertrophy (LVH; arrow); B – apical 4-chamber view demonstrating concentric LVH (arrows); C – continuous-wave Doppler across the left ventricular outflow tract (LVOT), demonstrating a late-peaking systolic jet (peak gradient of 52 mm Hg), consistent with significant dynamic LVOT obstruction (arrows); D – parasternal short-axis view at the level of papillary muscles, showing LVH and prominent papillary muscles (arrows)

Cardiac magnetic resonance (CMR) confirmed LV myocardial thickening (up to 14 mm in the inferoseptal segments). Short tau inversion recovery sequences showed no myocardial edema, and late gadolinium enhancement demonstrated no signs of fibrosis.

Brain MR imaging identified isolated supratentorial white matter hyperintensities, with the largest lesion (up to 5 mm in diameter) located in the right frontoparietal subcortical region, consistent with nonspecific, most likely microangiopathic, demyelinating-type lesions. No other relevant abnormalities were observed.

Due to the presence of LVOTO, low-dose β-blocker therapy (bisoprolol at a dose of 2.5 mg/day) was initiated, with instructions to increase the dose under blood pressure and heart rate control. Adequate hydration and avoidance of volume depletion were also recommended.

This case highlights the complex cardiac phenotype of Fabry disease and diagnostic challenges posed by its phenotypic overlap with hypertrophic cardiomyopathy (HCM). Despite an absence of cardiac symptoms, the patient exhibited significant LVOTO secondary to concentric myocardial hypertrophy—findings typically suggestive of HCM.

Advanced cardiac imaging (echocardiography and CMR) enabled detailed phenotypic characterization, while genetic testing confirmed the diagnosis of FD.

This report underscores the importance of including lysosomal storage diseases in the differential diagnosis of HCM, particularly in women, where random X-chromosome inactivation may result in a full-scale clinical phenotype, despite delayed onset and a lack of systemic manifestations.

Early diagnosis and prompt initiation of causal therapy (enzyme replacement therapy or pharmacologic chaperones) are essential to slow organ damage progression and improve prognosis.