This report describes peroxisome biogenesis disorder 2A (PBD2A), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX5, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex5, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human PEX5 gene has not been introduced into flies.
Animals homozygous or hemizygous for loss-of-function mutations in the Dmel\Pex5 gene typically die during the embryonic and larval stages. In embryos, defects are observed in the ventral nerve cord, the PNS, glial cells, and in the some parts of the developing musculature. Loss-of-function mutant animals exhibit an inability to assemble functional peroxisomes. Glial-specific RNAi knockdown of Dmel\Pex5 resulted in axonal swelling and age-dependent locomotion defects. Physical interactions have been described for Dmel\Pex5; see below and in the Pex5 gene report.
[updated Apr. 2025 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]
[PEROXISOME BIOGENESIS DISORDER 2A (ZELLWEGER); PBD2A](https://omim.org/entry/214110)
[PEROXISOME BIOGENESIS FACTOR 5; PEX5](https://omim.org/entry/600414)
PBD2A is one of a group of peroxisome biogenesis disorders characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction. In its most severe form, Zellweger syndrome, affected individuals die in the first year. [from MIM:214100; 15.08.10]
PBD2A is autosomal recessive and is caused by mutations in the Hsap\PEX5 gene. [from MIM:214100; 15.08.10]
The product of the PEX5 gene binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. [from Gene_cards:PEX5, 2015.09.09]
PBD2A is is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. [from MIM:214100; 15.08.10]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PEX5 (1 Drosophila to 1 human). Dmel\Pex5 shares 36% identity and 51% similarity with human PEX5; there is an additional more distantly related gene in human.
