Introduction

This chapter is about the effects on the central nervous system (CNS) of inborn errors of metabolism (IEM). IEM are a large number of rare genetic disorders caused by biochemical errors. The genes that code for enzymes that convert substances (substrates) into specific products are defective. Disease is caused either by the defect/absence of a specific enzyme that disrupts a metabolic pathway causing abnormal build-up of substrate in cells or by the defect/absence of important proteins or enzymes that help in the synthesis of essential compounds.

Inborn errors of metabolism can be categorized into disorders of carbohydrate metabolism (e.g. galactosemia), amino acid metabolism (e.g. phenylketonuria and maple syrup urine disease), lysosomal storage, peroxisomal function, and a myriad of others not covered in this chapter. Although the majority of IEM have some CNS effects, this chapter will concentrate on lysosomal storage disorders and peroxisomal disorders because of the known CNS effects on neuropsychological function and development in both untreated and treated individuals and because of the advances in diagnosis and treatment with improved outcomes for these categories of diseases.

In the past 25 years, inborn errors of metabolism that affect the CNS have been the first genetic diseases to have effective treatments. The first treatments for these disorders were alterations in diet for a number of these diseases such as phenylketonuria and maple syrup urine disease, resulting in prevention of mental retardation.