diagnosis of human peroxisomal biogenesis disorders: molecular understanding of peroxisome

peroxisomes are single membrane bound organelles present in a wide variety of eukaryotes from yeast to human, have different functions, two of which are well conserved, i.e. hydrogen peroxide decomposition and fatty acid beta-oxidation. the process of peroxisome biogenesis can be divided into distinct steps including peroxisome membrane assembly, import of matrix proteins and peroxisome proliferation. genetic and proteomic approaches have led to the identification of 32 conserved proteins called peroxins which are required for different steps of peroxisome biogenesis. the peroxisomal disorders represent a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. peroxisome biogenesis disorders (pbds) are comprised of four different disorders including zellweger syndrome (zs), neonatal adrenoleukodystrophy (nald), infantile refsum’s disease (ird), and rhizomelic chondrodysplasia punctata (rcdp). the principal molecular defects responsible for pbds lie primarily in peroxins which are essential factors for protein targeting, docking, import, receptor recycling or synthesis of peroxisome membranes. among pbds, zellweger syndrome, the most severe form presents defects in peroxisomal protein import resulting in hypotonia, craniofacial dysmorphology and neurological abnormalities. so far, no curative therapy is available but parental diagnosis can be done by biochemical testing.