Laboratory diagnosis of fabry disease

Abstract

The definitive diagnosis of Fabry disease in male patients is normally made by demonstrating a deficiency of α-galactosidase A in a blood sample, which may be white blood cells, plasma/serum or a dried blood spot. The diagnosis is confirmed by mutational analysis. The enzymatic assay is unreliable for detecting female carriers, who can only be diagnosed reliably by mutational analysis. The measurement of the storage products, globotriaosylceramide (Gb3) in plasma and urine or globotriaosylsphingosine (lyso-Gb 3) in plasma can often provide support for a diagnosis and is useful for monitoring treatment. Methods for mass or high-risk screening have been developed based on measuring the α-galactosidase A activity and/or protein in dried blood spots or the storage products in urine collected on filter paper. In the future the detection of mutations in the α-galactosidase A using high-throughput methods for analysing DNA might be the first step rather than a confirmatory one in the diagnosis of Fabry disease. © 2010 Springer Science+Business Media B.V.