Introduction: Fabry disease (FD) is a rare genetic di-sorder, caused by X-linked inherited mutations in the GLA gene, encoding a lysosomal hydrolase, alpha ga-lactosidase A (AGAL-A). The non-classical forms are usually underdiagnosed, having a higher residual acti-vity, with a late onset.
Objective: We report an atypical case of late onset FD with obstructive hypertrophic cardiomyopathy (HCM) and advanced fibrosis, evolving with complete atrio-ventricular block (CAVB), identified by transthoracic echocardiography (TTE) and cardiac magnetic reso-nance (CMR) and confirmed by genetic analyses.
Case presentation: A 65-year-old male patient, pre-sented with effort angina pectoris, dyspnea and recur-rent syncope. Clinical examination revealed a crescen-do–decrescendo mid-systolic heart murmur between the apex and left sternal border. The ECG showed sinus bradycardia and left ventricular hypertrophy (LVH), with strain pattern. Blood tests detected an increa-sed NTproBNP (7047 pg/ml) and a normal troponin I. TTE confirmed LVH, with an asymmetrical pattern (septum-21 mm) and preserved left ventricular ejecti-on fraction (LVEF). We noted papillary muscles hyper-trophy (PMH) and an unusual left ventricle outflow tract (LVOT) obstruction, due to a systolic anterior motion of mitral chordae tendineae, with a dynamic pressure gradient of 37 mmHg, increased after Valsalva manoeuver to 57 mmHg. LV global longitudinal strain was decreased (-16%), with the lowest values in the in-ferior and infero-lateral, basal and mid-basal segments. The CMR certified HCM, with a LV mass of 139 g/m², LVEF of 73%, adding diffuse late gadolinium enhan-cement with a prominent focus within the mid basal infero-lateral mid-wall segment. We decided in favor of surgery, the medical treatment being limited by per-sistent bradycardia. However, the patient developed CAVB, being cardiostimulated (DDD). After pacing the LVOT gradient normalized, with complete resoluti-on of symptoms. High QRS voltage with marked repo-larization abnormalities, CAVB, associated with PMH and infero-lateral impairment of myocardial deforma-tion, with corresponding intramural fibrosis at CMR raised the suspicion of FD. Genetic analysis consisting of a next generation sequencing cardio-panel, identi-fied a pathogenic hemizygous mutation in exon 3 of GLA gene, c.416A >G (p.N139S). In dried blood spot, AGAL-A activity was decreased by 46% (1,8 μmol/l/h), with increased lyso-Gb3 (1,5 ng/ml).
Conclusions: TTE and CMR give us important „red flags“ for FD in patients with hypertrophic cardiomyo-pathy, combined with ECG and clinical criteria. Early screening for FD in high risk patients, with HCM and highly suggestive imagistic criteria is very important, in order to start the enzyme replacement therapy befo-re development of irreversible organ damages.