Peroxisomes are cellular organelles that carry out important functions such as lipid metabolism and metabolic oxidations. A group of genetic disorders, known as peroxisome biogenesis disorders (PBD), affect the membrane biogenesis and fission of the peroxisomes, thereby resulting in mild to severe phenotypic defects. Zellweger Syndrome (ZS) is the most severe of these PBDs. Unfortunately, it is also the most common of the PBDs occurring in early infancy. Infants born with ZS present with generalized hypotonia, hepatomegaly, hepatic dysfunction, and neurological abnormalities, including seizures. Since the peroxisomes play a vital role in clearing the cells' toxic metabolites, most of the above mentioned clinical features result from a reduction or elimination of peroxisomes causing very high build up of iron and copper in the body tissues. The most characteristic feature of ZS is the typical facies of infants with this condition. These facial deformities include a high forehead, deformed earlobes, underdeveloped ridges of the eyebrows, large anterior fontanelle, and a flat looking face. In some cases, infants may even be born with glaucoma, impaired hearing, and/or chondrodysplasia punctata.
The process of peroxisomal biogenesis and protein import into the organelle is not very clearly known. However, it is understood that at least 29 different genes are involved in these processes. Mutations in at least 12 of these genes have been shown to result in ZS; three of them (PEX3, PEX16, and PEX9) interfering with membrane biogenesis and the remaining nine (PEX1, PEX2, PEX5, PEX6, PEX10, PEX12, PEX13, PEX14, and PEX26) expected to play some part in the protein import. Of these, PEX1 gene mutations are the most common and they are associated with Peroxisome biogenesis disorder 1A (PBD1A).