β-Galactosidase Deficiency: G_M1 Gangliosidosis, Morquio B Disease, and Galactosialidosis

This chapter focuses on certain lysosomal diseases, in particular, G_M1 gangliosidosis, Morquio B disease, and galactosialidosis, caused by mutations in genes coding for lysosomal β-galactosidases. The chapter discusses certain glycosaminoglycans, their structure and the enzymes required for their degradation, and the disease related to mutations affecting these degradative enzymes. The various lysosomal hydrolases enzymes involved are discussed, as well as their protective proteins, protective protein/cathepsin A (PPCA, known also as PPGB [protective protein for β-galactosidase], or as cathepsin A or lysosomal carboxypeptidase). The clinical phenotypes resulting from damage to these enzymes or protective proteins are discussed in some detail along with the approach to diagnosis and the diagnostic tests required, and the nature and structure of the stored substrates. The rapidly increasing number of mutations is discussed along with their worldwide distribution. Therapy of these disorders is challenging but there have been some successes, and these are discussed. The chapter has been updated and new references added. Six of the 55 references are new, four of them from 2013 and 2014. The work will be useful for a wide variety of readers, including clinicians, biochemists, molecular geneticists and epidemiologists.