Metabolic Disease

Treatment approaches for metabolic disorders include (a) modifying the diet to limit the amount of a precursor that is not metabolized properly; (b) using cofactors or vitamins to enhance the residual activity of a defective enzyme system; (c) using detoxifying agents to provide alternative pathways for the removal of toxic intermediates; (d) enzyme replacement, to provide functional enzymes exogenously (from the outside); (e) organ transplantation, which in principle allows for endogenous (internal) production of functional enzymes; and (f) gene therapy, or replacement of the defective gene.

Gene therapy is expected to become the most important approach. It offers the potential for definitive treatment, and it is being actively investigated as a treatment for virtually every one of the metabolic disorders. Most of the genes for the enzymes involved in metabolic diseases have been identified and cloned, and in many cases the genes can be replaced in experimental systems. Genetic approaches have been used to produce mass quantities of enzymes to use for enzyme replacement, but as of 2002, gene therapy has not yet been used successfully to provide the stable expression of active enzymes in the human body.

This chapter will summarize classes of inborn errors of metabolism based upon the type of chemical process involved, and individual disorders will be discussed that illustrate the various disease mechanisms and treatment approaches.