BIOCHEMICAL DIAGNOSTIC STRATEGY IN FEMALES SUSPECTED OF FABRY DISEASE
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Study objective and method
To demonstrate
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The benefits of adding lyso-GL-3 | to ► | ![]() |
Primary diagnostic for testing | for ► |
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Improving detection rate of potential females with FD
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First large prospective study
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11,948 females with suspicion of FD tested for |
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Biochemical tests
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followed by | ![]() |
Genetic confirmatory testing in 883 females | ![]() |
Groups |
01. Low α-Gal A activity High lyso-GL-3 | 02. Low α-Gal A activity Normal lyso-GL-3 | 03. Normal α-Gal A activity High lyso-GL-3 | 04. Normal α-Gal A activity Normal lyso-GL-3 |
Classical FD very likely (n=61) | Classical FD unlikely (n=184) | FD very likely (n=256) | ![]() had normal results (n=11,447*) |
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Genetic confirmatory test | No further testing required |
Results
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(184/883) females were identified with one or two GLA variants. |
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Distribution of genetically positive samples
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Better indicator of FD | |||||
Elevated lyso-GL-3 levels (39% PPV) |
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Low α-Gal A activity (6% PPV) |
Clearly negative results for both biochemical parameters: Unlikely to have FD, even in clinically highly suspicious cases |
Proposed diagnosis decision tree
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STEP 2
Once enzyme deficiency is confirmed, molecular testing is performed to identify GLA genetic variants.
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STEP 2
Once enzyme activity (deficient or not) together with elevated biomarker is confirmed, molecular testing is performed to identify GLA genetic variants.
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Conclusion
*Mutation analysis performed in 389 cases.
α-Gal A: Alpha-galactosidase A; dbFGP: Fabry disease genotype–phenotype database; FD: Fabry disease; Lyso-GL-3: Globotriaosylsphingosine; PPV: Positive predictive value; DBS: Dried blood spotting; GLA: Galactosidase alpha; VUS: Variant of unknown significance.