Severe Changes in Polyunsaturated Fatty Acids in the Brain, Liver, Kidney, and Retina in Patients with Peroxisomal Disorders

Abstract

Peroxisomal disorders are a new group of congenital diseases in which peroxisomes are deficient in numbers or functionality. The prototype of these disorders is Zellweger syndrome (ZS), an extremely severe disease involving the central nervous system, liver, and kidneys (cerebro-hepato-renal syndrome). Infants with ZS have profound psychomotor retardation and hypotonia from birth, and very soon become blind and deaf. They usually die during the first year of life; autopsy examination reveals dysmyelination, gliosis, and neuronal heterotopias. Peroxisomes are absent from hepatocytes and proximal renal tubules (Goldfischer et al., 1973). The deficiencies in peroxisomal enzymes cause multiple biochemical abnormalities. In relation to lipid metabolism, there is accumulation of very long-chain fatty acids (Brown et al., 1982) due to a deficient peroxisomal ß-oxidation system (Singh et al., 1984) and a decrease in plasmalogen levels (Heymans et al., 1983) attributable to a defect in dihydroxy-acetone phosphate acyltransferase (Datta et al., 1984).