Peroxisomal disorders are a group of genetical diseases which are characterized by the absence of normal peroxisomes in the cells of the body. Peroxisomes are oxidative organelles that are present in all tissues cells but are especially abundant in the liver and kidney. Peroxisomal disorders are caused by defects in single enzymes which are important for peroxisome function or in peroxins, proteins encoded by PEX genes that are critical for normal peroxisome assembly and biogenesis. About 90% of the peroxisomal disorders are autosomal recessive developmental brain disorders that also result in skeletal and craniofacial dysmorphism, liver dysfunction, progressive sensorineural hearing loss, and retinopathy. Most peroxisomal disorders cause severe neurological dysfunction due to CNS malformations (migration defects), myelin abnormalities, and neuronal degeneration.
Peroxisomal enzymes catalyze several anabolic and catabolic reactions. The most important of these are plasmalogen synthesis and very long chain fatty acid (VLCFA) beta oxidation. Plasmalogens are the most abundant phospholipids in myelin. The products of VLCFA beta oxidation are used for biosynthesis of cholesterol, bile acids, and other compounds. The peroxisome has a single membrane which encloses the peroxisomal matrix. There are two types of peroxisomal disorders: single peroxisomal enzyme deficiencies and peroxisomal biogenesis disorders (PBDs). The former are caused by mutations of genes encoding specific peroxisomal enzymes. PBDs are caused by mutations of PEX genes that are involved in the biogenesis and function of peroxisomes and are characterized by deficiencies of multiple peroxisomal enzymes and, in some cases, by absence or reduction in the number of peroxisomes.