PEROXISOMAL DISORDERS

The concept that there are human disease states that are associated with abnormal peroxisomal function is of recent origin. This is due in part to the relatively recent discovery of the organelle itself by de Duve in 1983, and to the earlier belief that it was a vestigial structure in mammals. The recognition that the organelle is significant in mammals was ushered in by Paul Lazarow's observation that rat peroxisomes catalyze the beta-oxidation of fatty acids. By 1981, more than 40 enzymes had been localized to the peroxisome, and the number continues to grow. Respect for the physiological role of the peroxisome in man has been heightened by our recent recognition that peroxisome malfunction causes profound disturbances. The Zellweger cerebro-hepato-renal syndrome represents the most serious peroxisomal disease. It is associated with malfunction of virtually every organ, and children with the disease usually do not survive beyond the 4th month. Application of newly developed diagnostic techniques has shown that the clinical spectrum and frequency of peroxisomal disorders are greater than had been realized. Eleven separate peroxisomal disorders have now been identified. Our laboratory alone has identified more than 2000 patients. Disturbances of very long chain fatty acid and ether phospholipid metabolism are present in 9 of the 11 peroxisomal disorders. In this presentation, we will provide an overview of the peroxisomal disorders, with emphasis on disturbances of fatty acid and ether lipid metabolism.