Looking for Fabry, Finding More: LVH Screening Yields Unexpected Gaucher Diagnosis

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity, which can manifest as left ventricular hypertrophy (LVH). We aimed to assess the prevalence of FD in an unselected cohort of patients with unexplained LVH.

We screened 202 unrelated adults with LVH using enzymatic assays for α-galactosidase A in dried blood spots. Patients with low activity underwent GLA gene sequencing. Echocardiographic parameters were evaluated according to ESC guidelines. FD was diagnosed in 4 women (2%), each carrying distinct pathogenic GLA mutations. All affected individuals showed normal or borderline enzyme activity. Cardiac, renal, or neurological symptoms were observed variably among patients. Echocardiographic findings revealed slightly lower wall thickness and preserved systolic function in FD patients compared to those without FD. Cascade genetic screening identified 16 additional family members with the same mutations. One patient (0.5%) was incidentally diagnosed with Gaucher disease based on syndromic features and enzymatic testing.

FD was identified in 2% of patients with unexplained LVH, who were females. Enzyme-based screening followed by targeted genetic testing is a cost-effective strategy for FD detection. Early diagnosis is essential for prompt treatment and family counselling, underscoring the importance of routine FD screening in patients with LVH of unclear aetiology. Our findings support the use of targeted screening for Fabry disease in patients with LVH and systemic features, and highlight the potential to identify other lysosomal disorders in selected cases.