I. Introductory concepts
These disorders are generally associated with specific metabolic abnormalities and result in blockage of amino acid, carbohydrate or lipid metabolism, or deficiency in oxidative phosphorylation. Functional and/or morphologic changes may occur and in some instances may be ameliorated by therapy. In many disorders the carrier state can be identified to permit genetic counseling. Many of these disorders have a clinical expression in children who are normal at birth, but who begin to miss developmental milestones during infancy or childhood.
The three major categories are:
Neuronal storage diseases – mostly autosomal recessive diseases involving deficiency of a specific enzyme, often a lysosomal enzyme, and accumulation of the enzyme substrate. Gray matter, usually involving cortical neurons, is primarily involved.
Leukodystrophies –characterized by selective involvement of myelin and white matter involvement. Most leukodystrophies (except for X-linked adrenoleukodystrophy) are autosomal recessive diseases. Diffuse involvement of white matter leads to a variety of clinical expression.
Mitochondrial encephalomyopathies – disorders involving oxidative phosphorylation and usually resulting from mutations in the mitochondrial genome. They typically involve gray matter and skeletal muscle and are covered with Skeletal Muscle Disorders.