Peroxisomal disorders

A growing number of inherited disorders causing severe and progressive neurological deficits are linked to peroxisomal dysfunction. More than 15 peroxisomal diseases with neurological manifestations and some of them with dysmorphic features are identified. The diseases are classified into three groups depending on some similarities in the pathophysiology of the diseases within each group: defective assembly of the organelle resulting in impairment of multiple peroxisomal functions (group I); peroxisomes present and loss of several peroxisomal enzyme functions (group II); peroxisomes present and loss of a single peroxisomal enzym function (group III). Apparently similar clinical phenotypes may correspond to different biochemical deficits, and the same biochemical defect(s) can be associated with different clinical phenotypes. With the study of human peroxisomal diseases, advances have been gained as to the function of the peroxisome in normal and pathological conditions. Most important functions of peroxisomes in humans include β-oxidation of very long chain fatty acids and fatty acid derivatives, ether-phospholipid biosynthesis, pipecolic acid degradation, phytanic acid oxidation, and glyoxylate detoxification. Knowledge about the molecular basis of the diseases is now in progress substantiated by yeast mutant models, since the affected genes involved are conserved from yeasts to humans.