Fabry Disease: A Metabolic Proteinuric Nephropathy

The -galactosidase A gene (GLA) is located on the minus strand of the chromosome X on the locus Xq22.1.The GLA gene is 10,223 base pairs long and contains 7 exons.GLA gene www.intechopen.comAdvances in the Study of Genetic Disorders 256 may give rise to 7 different processed transcripts by alternative splicing.However, just one of these encodes the 429-aminoacid lysosomal -Gal A with a molecular mass of 48.7 kD.Fig. 1.A) -galactosidase A catalyzes the hydrolytic cleavage of the terminal galactose from globotriaosylceramide (Gb3).B) The deficiency of -galactosidase leads to accumulation of Gb3 and other glycosphingolipids, such as lyso-globotriaosylceramide (lyso-Gb3) Within the coding region, 239 single nucleotide polymorphisms present in the general population and more than 400 GLA mutations that lead to Fabry disease have been found.Exons 5, 6 and 3 comprise the majority of point mutations respectively.Missense mutations may be classified in 3 groups in accordance with the effect they have on the protein function (Garman & Garboczi, 2004).First, mutations that alter the active site of the enzyme; second, mutation that interfere with the correct folding and stability of the protein; and finally, the remaining mutations that negatively affect the function of the enzyme.The nature of the mutation may influence therapeutic approaches.Most mutations are family-specific, which explains the marked variability in the residual enzyme activity and precludes the use of a single, fast genetic testing technique.Rather, the whole gene should be sequenced. Clinical manifestations of Fabry disease Early clinical featuresAlthough glycolipid accumulation begins in the prenatal period, symptoms of the classic form of Fabry disease do not arise until childhood (Vedder et al., 2006).Symptoms include www.intechopen.com