Congenital metabolic diseases. Lysosomal storage diseases

Abstract

The classification and epidemiology of hereditary metabolic disorders are presented. That is a large group consisting from more them 800 monogenic diseases, each of which caused by inherited deficiency of certain metabolic fate. Many of these disorders are extremely rare, but their total incidence in the population is close to 1:10005000. Lysosomal storage diseases (LSD) resulting from inherited deficiency in lysosomal functions occupy a special place among hereditary metabolic disorders. The defects of catabolism cause the accumulation of undigested or partially digested macromolecules in lysosomes (that is, storage), which can result in cellular damage. About 60 diseases take part in this group with total incidence of about 1:70008000. LSDs typically present in infancy and childhood, although adult-onset forms also occur. Most of them have a progressive neurodegenerative clinical course, although symptoms in other organ systems are frequent. The etiology and pathogenetic aspects of their main clinical entities: mucopolysaccharidosis, glycolipidosis, mucolipidosis, glycoproteinosis, etc, are presented. Mucopolysaccharidoses caused by malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans are more frequent among LSD. Sphingolipidoses caused by defects of lipid catabolism are second for frequency group of LSD. The state-of-art in field of newborn screening. clinical, biochemical and molecular diagnostics of these grave diseases are discussed. The main directions of modern lysosomal storage diseases therapy are characterized: transplantation of hematopoietic stem cells; enzyme replacement therapy; therapy with limitation of substrate synthesis (substrate-reducing therapy); pharmacological chaperone therapy. Perspective directions for LSD therapy are gene therapy and genome editing which are at advanced preclinical stages.