How can I differentiate between Fabry disease and other lysosomal storage disorders during initial assessment?

During the initial assessment, differentiating Fabry disease from other lysosomal storage disorders (LSDs) relies on recognising its unique multisystemic clinical features and targeted biochemical testing. Fabry disease often presents with non-specific gastrointestinal symptoms such as abdominal pain and diarrhoea, which can overlap with other LSDs but are accompanied by characteristic signs including angiokeratomas, acroparesthesias (burning pain in hands and feet), corneal verticillata, and progressive renal and cardiac involvement ¹ (Hilz et al., 2018; Lenders and Brand, 2022). These multisystemic manifestations are less common or present differently in other LSDs.

Biochemically, initial assessment should include measurement of alpha-galactosidase A enzyme activity in males, which is typically markedly reduced in Fabry disease, whereas other LSDs involve different enzyme deficiencies ¹. In females, enzyme activity may be normal or borderline, so genetic testing for GLA gene mutations is essential to confirm diagnosis (Lenders and Brand, 2022). Other LSDs require different enzyme assays and genetic panels, so a focused clinical suspicion based on the pattern of organ involvement guides the choice of tests.

Therefore, the key to differentiation at initial assessment is a thorough clinical evaluation for Fabry-specific signs combined with targeted enzyme and genetic testing, distinguishing it from other LSDs that have distinct clinical and biochemical profiles ¹ (Hilz et al., 2018; Lenders and Brand, 2022).