Fast Five Quiz: Fabry Disease Presentation and Diagnosis

Helmi L. Lutsep, MD


April 06, 2021

Figure 1. Light micrograph of a section through an angiokeratoma, a rare vascular lesion of capillaries (orange) in the dermis that causes dark red spots on the skin. It also causes secondary epidermal changes, including hyperkeratosis (red, top), a thickening of the top layer of the skin.

In males, alpha-galactosidase assays are used to diagnose Fabry disease. Enzyme activity can be measured using the patient's serum, leukocytes, tears, or cultured fibroblasts. However, enzyme assays identify only two thirds of heterozygote female patients. Because levels of Gb3 and alpha-galactosidase A may be normal in female (heterozygote) patients, genetic and/or molecular diagnosis is necessary to confirm Fabry disease in female patients with clinical features.

Female patients with Fabry disease who present with neurologic symptoms and pain may be misdiagnosed. This trend may be due to the X-linked pattern of inheritance in Fabry disease. Historically, it was thought that females with GLA pathogenic variants were merely carriers of Fabry disease. Larralde and colleagues consider Fabry disease a possible storage disease transmitted as an X-linked–dominant, not X-linked–recessive, disease.

The classic cutaneous phenotype, angiokeratoma corporis diffusum, is seen less commonly in female patients.

Learn more about the genetics of Fabry disease.


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