This enzyme is a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose.
Two enzyme replacement therapies are available to functionally compensate for alpha-galactosidase deficiency. Agalsidase alpha and beta are both recombinant forms of the human α-galactosidase A enzyme and both have the same amino acid sequence as the native enzyme. Agalsidase alpha and beta differ in the structures of their oligosaccharide side chains.
The pharmaceutical company Shire manufactures agalsidase alpha under the brand name Replagal as a treatment for Fabry's disease, and was granted marketing approval in the EU in 2001. FDA approval was applied for the United States. However in 2012, Shire withdrew their application for approval in the United States citing that the agency will require additional clinical trials before approval.
The pharmaceutical company Genzyme produces synthetic agalsidase beta under the brand name Fabrazyme for treatment of Fabry's disease. In 2009, contamination at Genzyme's Allston, Massachusetts plant caused a worldwide shortage of Fabrazyme, and supplies were rationed to patients at one-third the recommended dose. Some patients have petitioned to break the company's patent on the drug under the "march-in" provisions of the Bayh–Dole Act.
Naumoff DG (2004). "Phylogenetic analysis of α-galactosidases of the GH27 family". Molecular Biology (Engl Transl)38 (3): 388–399. PMID15285616.PDF
Eng CM, Desnick RJ (1994). "Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene.". Hum. Mutat.3 (2): 103–11. doi:10.1002/humu.1380030204. PMID7911050.
Caillaud C, Poenaru L (2002). "[Gaucher's and Fabry's diseases: biochemical and genetic aspects]". J. Soc. Biol.196 (2): 135–40. PMID12360742.
Germain DP (2002). "[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]". J. Soc. Biol.196 (2): 161–73. PMID12360745.
Schaefer E, Mehta A, Gal A (2005). "Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey.". Acta paediatrica (Oslo, Norway : 1992). Supplement94 (447): 87–92; discussion 79. doi:10.1080/08035320510031045. PMID15895718.
Lidove O, Joly D, Barbey F, et al. (2007). "Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature.". Int. J. Clin. Pract.61 (2): 293–302. doi:10.1111/j.1742-1241.2006.01237.x. PMID17263716.
Dean KJ, Sweeley CC (1979). "Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates.". J. Biol. Chem.254 (20): 9994–10000. PMID39940.
Ishii S, Sakuraba H, Suzuki Y (1992). "Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.". Hum. Genet.89 (1): 29–32. doi:10.1007/BF00207037. PMID1315715.
Ioannou YA, Bishop DF, Desnick RJ (1992). "Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion.". J. Cell Biol.119 (5): 1137–50. doi:10.1083/jcb.119.5.1137. PMC2289730. PMID1332979.
von Scheidt W, Eng CM, Fitzmaurice TF, et al. (1991). "An atypical variant of Fabry's disease with manifestations confined to the myocardium.". N. Engl. J. Med.324 (6): 395–9. doi:10.1056/NEJM199102073240607. PMID1846223.
Koide T, Ishiura M, Iwai K, et al. (1990). "A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser.". FEBS Lett.259 (2): 353–6. doi:10.1016/0014-5793(90)80046-L. PMID2152885.
Kornreich R, Bishop DF, Desnick RJ (1990). "Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene.". J. Biol. Chem.265 (16): 9319–26. PMID2160973.
Sakuraba H, Oshima A, Fukuhara Y, et al. (1990). "Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease.". Am. J. Hum. Genet.47 (5): 784–9. PMC1683686. PMID2171331.
Bernstein HS, Bishop DF, Astrin KH, et al. (1989). "Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene.". J. Clin. Invest.83 (4): 1390–9. doi:10.1172/JCI114027. PMC303833. PMID2539398.
Bishop DF, Kornreich R, Desnick RJ (1988). "Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region.". Proc. Natl. Acad. Sci. U.S.A.85 (11): 3903–7. doi:10.1073/pnas.85.11.3903. PMC280328. PMID2836863.
Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH (1988). "A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A.". Gene58 (2-3): 177–88. doi:10.1016/0378-1119(87)90374-X. PMID2892762.
Bishop DF, Calhoun DH, Bernstein HS, et al. (1986). "Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme.". Proc. Natl. Acad. Sci. U.S.A.83 (13): 4859–63. doi:10.1073/pnas.83.13.4859. PMC323842. PMID3014515.
Lemansky P, Bishop DF, Desnick RJ, et al. (1987). "Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease.". J. Biol. Chem.262 (5): 2062–5. PMID3029062.