Molecular Characterization of Peroxisome Biogenesis Disorders with Zellweger Syndrome Spectrum

Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) are constituted of threedifferent phenotypically disorders: Zellweger syndrome (ZS), the most severe; neonataladrenoleukodystrophy (NALD); and infantile refsum disease (IRD), the least severe, that have beenoriginally described based on their biochemical and molecular bases of these disorders which hadbeen fully determined. Individuals with PBD, ZSS usually come to clinical attention in the newbornperiod or later in childhood. The diagnosis of PBD, ZSS can be definitively determined bybiochemical assays. Measurement of plasma very-long-chain fatty acid (VLCFA) levels is the mostcommonly used and most informative initial screen. Mutations in thirteen different PEX genes - thosethat encode peroxins, the proteins required for normal peroxisome assembly - have been identified inPBD, ZSS. Mutations in PEX1, the most common cause of PBD, ZSS, are observed in about 68% ofaffected individuals. Sequence analysis is available clinically for the following seven genes: PEX1,PXMP3 (PEX2), PRXR1 (PEX5), PEX6, PEX10, PEX12, and PEX26.