Biochemically supported diagnosis of Fabry disease in a young adult with unexplained left ventricular hypertrophy: a diagnostic challenge

Abstract

Fabry disease (OMIM #301500) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, resulting in deficient activity of α-galactosidase A. This enzymatic defect leads to lysosomal glycosphingolipid accumulation and progressive multisystem dysfunction. The clinical manifestations are variable and non-specific, which may delay diagnosis. We report a 29-year-old Malay man who presented with recurrent palpitations, exertional chest pain, dyspnoea and fatigue. The physical examination was unremarkable, and there was no known relevant family history. Cardiac magnetic resonance imaging demonstrated significant concentric left ventricular hypertrophy with markedly reduced native myocardial T1 values. No significant coronary artery abnormalities were identified, raising suspicion of an infiltrative or metabolic cardiomyopathy. Plasma α-galactosidase A activity was markedly reduced at 0.3 nmol/mL/h (reference interval, 2.0–10.0 nmol/mL/h), which, together with the compatible cardiac imaging findings, strongly supported a diagnosis of Fabry disease, although molecular confirmation was unavailable. This case highlights a cardiac-predominant presentation strongly supportive of Fabry disease in a young Malaysian adult without documented classical extracardiac manifestations or a known relevant family history. It underscores the importance of considering Fabry disease in young patients with otherwise unexplained left ventricular hypertrophy and characteristic cardiac magnetic resonance findings. Early recognition is important to facilitate molecular confirmation, family screening and timely consideration of disease-specific management before irreversible organ damage develops.