PO42 Syncope and left ventricular hypertrophy: red flags for early diagnosis

Introduction Fabry disease is an X-linked lysosomal storage disorder caused by GLA gene mutations, leading to deficient alpha-galactosidase A activity. This results in systemic glycosphingolipid accumulation, affecting multiple organs. The p.Phe113Leu variant is the most common mutation in Portugal and is linked to the late-onset form of Fabry disease, typically manifesting as cardiac involvement in adulthood. Case Presentation A 58-year-old male with no significant medical history presented to the emergency department with episodes of pre-syncope. On admission, electrocardiogram showed a short PR interval, bifascicular block and telemetry revealed intermittent 2:1 and 3:1 atrioventricular (AV) block. Transthoracic echocardiogram revealed left ventricular (LV) hypertrophy (septum 18 mm), preserved systolic function, mild right ventricular hypertrophy and dilation of the aortic root and ascending aorta, with no other significant abnormalities. During hospitalization, the patient developed advanced AV block with syncope, requiring temporary pacemaker placement. Subsequently, the patient experienced non-sustained ventricular tachycardia, leading to dual-chamber implantable cardioverter-defibrillator (ICD) implantation. Given the hypertrophic phenotype and conduction system abnormalities, further investigation was performed, including serum biomarkers and scintigraphy to exclude cardiac amyloidosis and sarcoidosis. Cardiac MRI findings were impaired by ICD artefacts, but it was possible to document the presence of concentric LV hypertrophy and midwall/subepicardial late enhancement in the basal inferolateral wall and patchy mid myocardial enhancement in basal and mid interventricular septum. Finally, genetic testing identified the p.Phe113Leu variant in the GLA gene, diagnosing Fabry disease. Regarding family history, his mother received a permanent pacemaker in her 70s and his maternal grandfather died suddenly of unknown cause in his 40s. Conclusion This case highlights the importance of considering Fabry disease in patients presenting with LV hypertrophy and cardiac red flags like short PR interval, conduction abnormalities or aortic root dilatation, even in the absence of systemic symptoms like acroparesthesias, angiokeratomas, gastrointestinal or neurological involvement. Family history is important to recognise the genetic inheritance pattern and genetic testing is the most reliable Fabry disease test for all patients, since in females enzyme activity may be normal. Early diagnosis is crucial, as enzyme replacement therapy or chaperone therapy may modify disease progression.