This report describes peroxisome biogenesis disorder 5A (PBD5A), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX2, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex2, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. A disease model has also been established in mouse.
For loss-of-function mutations in the Dmel\Pex2 gene, as with loss of the human orthologue, mutants exhibit an inability to assemble functional peroxisomes.
[updated Oct. 2015 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 5A (ZELLWEGER); PBD5A](https://omim.org/entry/614866)
[PEROXISOME BIOGENESIS FACTOR 2; PEX2](https://omim.org/entry/170993)
PBD5A is one of a group of peroxisome biogenesis disorders that presents in infants with severe seizures, profound hypotonia, and inability to feed; additional characteristics are craniofacial and eye abnormalities, neuronal migration defects, enlarged liver, small size, and bone abnormalities. Affected individuals do not show significant development and usually die in the first year. [from MIM:614866; 15.08.10]
PBD5A is autosomal recessive and is caused by mutations in the Hsap\PEX2 gene. [from MIM:614866; 15.08.10]
Peroxisomes are missing in skin fibroblasts. from MIM:614866; 15.08.10]
PEX2 encodes an integral peroxisomal membrane protein which is thought to be involved in peroxisomal matrix protein import. [from Gene_cards:PEX2, 2015.09.09]
PBD5A is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. Very long chain fatty acids (VLCFA) were found in the serum of a patient; three peroxisomal beta-oxidation enzymes were missing in liver homogenates. [from MIM:614866; 15.08.10]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PEX2 (1 Drosophila to 1 human). Dmel\Pex2 shares 30% identity and 50% similarity with human PEX2.
