This report describes general characteristics of the group of diseases classified as peroxisome biogenesis disorders (PBD) or Zellweger syndrome spectrum (ZSS). Peroxisome biogenesis disorder is a genetically heterogeneous disorder, with multiple genes and mapped loci. A listing of PBD subtypes, as defined by OMIM, may be found in the table below, with links to more detailed reports for subtypes that have been investigated using fly models.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Newborns affected with Zellweger syndrome (ZS) are hypotonic, feed poorly, and have distinctive facies, seizures, and liver cysts with hepatic dysfunction. Bony stippling of the patella(e) and other long bones may occur. The neurological defects include demyelination, retinal dystrophy, hearing loss and seizures. Infants with ZS are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Older children have retinal dystrophy, sensorineural hearing loss, developmental delay with hypotonia, and liver dysfunction. The clinical courses of the milder forms of peroxisome biogenesis disorder, neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), are variable and may include developmental delays, hearing loss, vision impairment, liver dysfunction, episodes of hemorrhage, and intracranial bleeding. While some children can be very hypotonic, others learn to walk and talk. The condition is often slowly progressive [from GeneReviews, Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.09.09].
PBD syndrome is characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction. There are 4 main phenotypic classes of PBDs that were defined prior to the molecular characterization; three of them in order of severity, Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), form a spectrum of overlapping features. The most severely affected patients with classic Zellweger syndrome die within the first year. Zellweger syndrome is indicated by the "A" in the OMIM subtype designation; the less severe forms are indicated with a "B" in the OMIM subtype designation (BSC). The fourth class, rhizomelic chondrodysplasia punctata (RCDP1), displays a distinct PBD phenotype. [from MIM:214100; 15.08.10]
The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases. PBDs are caused by mutations in genes that encode peroxins, proteins required for the normal assembly of peroxisomes. Mutations in the PEX1 gene account for 68% of PBD cases and mutations in PEX6, PEX10, PEX12, and PEX26 account for another 26% of cases. [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.09.09].
PBD is a genetically heterogeneous autosomal recessive disorder that is caused by mutation to any one of several pexin genes; the pexin genes encode proteins necessary for peroxisome biogenesis. [from MIM:214100; 15.08.10]
As a result of impaired peroxisome function, an individual's tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in peroxisomes. The accumulation of these lipids can impair the normal function of multiple organ systems. In addition, these individuals can show deficient levels of plasmalogens. [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.09.09].
Liver peroxisomes are missing in Zellweger syndrome patients. [from MIM:214100; 15.08.10]
The signs and symptoms of Zellweger syndrome are due to the absence of functional peroxisomes within cells [from Genetics Home Reference, GHR_condition: zellweger-spectrum-disorder, 2015.09.09].
Very-long-chain fatty acids (VLCFA), which are usually oxidized in peroxisomes, accumulate in the cultured cells of patients with Zellweger syndrome or NALD. [from MIM:214100; 15.08.10]
