Chapter 6 Peroxisomal disorders

Abstract

Publisher Summary This chapter discusses the Zellweger syndrome, functions of peroxisomes in relation to the metabolic abnormalities in the Zellweger syndrome, classification of peroxisomal disorders, biogenesis of peroxisomes, topogenic signals on peroxisomal proteins, peroxisome assembly factors, and complementation analysis of cells from patients with defects in peroxisome biogenesis. In studies, at least 15 different genetic diseases in humans, in which peroxisomal functions are impaired, have been discovered. These diseases are divided into three distinct groups depending on whether there is a generalized loss of peroxisomal functions (group A), a loss of multiple peroxisomal functions (group B), or a loss of a single peroxisomal function (group C). The cerebro-hepato-renal (Zellweger) syndrome, the prototype of the peroxisomal disorders, is a multi-system disorder involving both embryofetopathy and progressive changes, which continue into postnatal life. The clinical presentation of the Zellweger syndrome is dominated in the first months of life by the typical craniofacial dysmorphia and profound neurological abnormalities. Group B comprises two diseases, rhizomelic chondrodysplasia punctata and the Zellweger-like syndrome. Rhizomelic chondrodysplasia is clinically characterized by a disproportionally short stature primarily affecting the proximal parts of the extremities, typical facial appearance, congenital contractures, characteristic ocular involvement, severe growth deficiency, and mental retardation. The group C peroxisomal disorders comprise diseases in which peroxisomes are present and only a single peroxisomal enzyme is deficient. This group includes X-linked adrenoleukodystrophy, the most frequently encountered of the peroxisomal disorders.