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

Area of Science:

• Genetics
• Cardiology
• Rare Diseases

Background:

• Fabry disease (FD) is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency.
• Left ventricular hypertrophy (LVH) can be a manifestation of Fabry disease.

Purpose of the Study:

• To determine the prevalence of Fabry disease in patients with unexplained LVH.
• To evaluate the effectiveness of enzyme-based screening followed by genetic testing for FD detection.

Main Methods:

• Enzymatic assays for alpha-galactosidase A activity were performed on dried blood spots from 202 adults with LVH.
• Patients with low enzyme activity underwent GLA gene sequencing.
• Echocardiographic parameters were assessed according to ESC guidelines.

Main Results:

• Fabry disease was diagnosed in 4 women (2%), all with distinct pathogenic GLA mutations and normal or borderline enzyme activity.
• Affected individuals presented with variable cardiac, renal, or neurological symptoms.
• Cascade genetic screening identified 16 additional family members with FD.
• One patient (0.5%) was incidentally diagnosed with Gaucher disease.

Conclusions:

• Fabry disease occurs in 2% of patients with unexplained LVH, primarily in females.
• Enzyme screening and genetic testing offer a cost-effective strategy for early FD detection.
• Routine screening for FD in LVH patients is crucial for timely treatment and family counseling.