Human Disorders of Peroxisome Biogenesis: Zellweger Spectrum and Rhizomelic Chondrodysplasia Punctata

The human peroxisome biogenesis disorders (PBD) are caused by autosomal recessive mutations in any of the 14 PEX genes, which encode peroxins, or PEX proteins, that act cooperatively to assemble functional peroxisomes. Mutations in PEX genes affect the import of peroxisome matrix enzymes and formation of new peroxisomes. The consequences are multiple enzyme deficiencies causing developmental malformations and progressive postnatal tissue injury. The PBD are classified into two distinct groups: Zellweger spectrum disorders (ZSD) and Rhizomelic Chondrodysplasia Punctata spectrum type 1 (RCDP1). The term “spectrum” is preferred because there is a gradation of phenotypes from severe to mild in these disorders, as well as newly recognized atypical phenotypes. In general, the milder the phenotype, the greater are the residual functions of the defective peroxin.