Peroxisome biogenesis disorders

The peroxisome biogenesis disorders (PBDs) neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the ZELLWEGER SYNDROME SPECTRUM. Most patients survive to adolesence and affected children experience HYPOTONIA but are able to achieve developmental milestones. In addition, craniofacial features are similar to but less pronounced than in Zellweger syndrome. Patients also may experience SEIZURES. and have renal cysts. In contrast to ZS, they may also develop SENSORINEURAL HEARING LOSS and RETINITIS PIGMENTOSA. Caused by mutations in the PEX genes. OMIM: 601539

Networked: 96 relevant articles (0 outcomes, 3 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Ciliopathies
2.	Peroxisomal Disorders (Peroxisomal Disorder)
3.	Zellweger Syndrome (Zellweger's Syndrome)
4.	Inborn Genetic Diseases (Disease, Hereditary)
5.	Protein Deficiency

Experts

1.	Fujiki, Yukio: 12 articles (01/2020 - 03/2002)
2.	Wanders, Ronald J A: 9 articles (01/2021 - 03/2002)
3.	Shimozawa, Nobuyuki: 7 articles (02/2019 - 03/2002)
4.	Ferdinandusse, Sacha: 6 articles (01/2021 - 08/2003)
5.	Waterham, Hans R: 6 articles (01/2021 - 01/2003)
6.	Baes, Myriam: 6 articles (01/2018 - 12/2006)
7.	Shimozawa, N: 6 articles (04/2007 - 02/2000)
8.	Tamura, Shigehiko: 5 articles (01/2020 - 08/2003)
9.	Fujiki, Y: 5 articles (10/2000 - 01/2000)
10.	Moser, Ann: 4 articles (05/2017 - 08/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Peroxisome biogenesis disorders:

1.	Proteins (Proteins, Gene)FDA Link 12/01/2006 - "During the past 10 years, several Pex genes have been knocked out in the mouse with the purpose to generate models to study the pathogenesis of peroxisome biogenesis disorders and/or to investigate the physiological importance of the Pex proteins. " 01/01/2023 - "Malfunctions of these proteins lead to severe diseases summarized as peroxisome biogenesis disorders. " 01/01/2021 - "Peroxisome biogenesis disorders (PBDs) are a group of metabolic developmental diseases caused by mutations in one or more genes encoding peroxisomal proteins. " 01/01/2020 - "Impaired peroxisome biogenesis, including defects of membrane assembly, import of peroxisomal matrix proteins, and division of peroxisome, causes peroxisome biogenesis disorders (PBDs). " 01/01/2017 - "Defects in peroxisomal protein import result in inherited peroxisome biogenesis disorders in humans. "
2.	Fatty Acids (Saturated Fatty Acids)IBA 02/01/2019 - "Here, we summarize current information related to peroxisomal diseases and ALD and introduce our efficient diagnostic system for use in Japan, which resulted in the diagnosis of 73 Japanese patients with peroxisome biogenesis disorders, 16 with impaired β-oxidation of fatty acids, three with impaired etherphospholipid biosynthesis, and 191 Japanese families with ALD so far." 04/01/2005 - "These findings are especially relevant for disorders in which branched-chain fatty acids accumulate, such as Refsum disease and peroxisome biogenesis disorders." 07/01/2009 - "Today, the study of peroxisome biogenesis disorders mainly focuses on metabolic defects such as accumulation of very long chain fatty acids or plasmalogen deficiency. " 11/16/2018 - "Despite the versatile metabolic functions of peroxisomes such as lipid synthesis and fatty acid oxidation and their relevance to genetically inherited diseases, namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there is not much research on peroxisome-targeting therapeutics. " 01/01/2022 - ": ABCD3/PMP70: ATP binding cassette subfamily D member 3; ACOX1: acyl-CoA oxidase 1; AP: autophagosome; COX: cytochrome c oxidase; CQ: chloroquine; CRISPRi: clustered regularly interspaced short palindromic repeats interference; DLBCL: diffuse large B-cell lymphoma; GO: gene ontology; dCas9: Cas9 endonuclease dead, or dead Cas9; HDACi: histone deacetylase inhibitors; IHC: Immunohistochemistry; LAMP2: lysosomal associated membrane protein 2; LCFAs: long-chain fatty acids; LFQ-MS: label-free quantitation mass spectrometry; LPC: lysophoshatidylcholine; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PBD: peroxisome biogenesis disorders; PTS1: peroxisomal targeting signal 1; ROS: reactive oxygen species; sgRNA: single guide RNA; VLCFAs: very-long chain fatty acids; Vor: vorinostat; WO: wash-off."
3.	PlasmalogensIBA 03/01/2023 - "Markedly reduced plasmalogens are a classic feature of peroxisome biogenesis disorders (PBD) because plasmalogen synthesis requires functional peroxisomes. " 10/13/2022 - "A lipidomics analysis of the inner ear revealed a local reduction in plasmalogens in the Pex3 mouse mutants, comparable to the systemic plasmalogen reduction reported in human peroxisome biogenesis disorders. " 07/01/2009 - "Today, the study of peroxisome biogenesis disorders mainly focuses on metabolic defects such as accumulation of very long chain fatty acids or plasmalogen deficiency. "
4.	Retinaldehyde (Retinal)IBA 12/10/2021 - "These proof-of-concept studies represent the first application of gene augmentation therapy to treat peroxisome biogenesis disorders and support the potential for retinal gene delivery to improve vision in these patients." 02/01/2016 - "Our study for the first time links peroxisome biogenesis disorders to retinal ciliopathies. "
5.	EnzymesIBA 05/01/2019 - "The importance of functional peroxisomes for cellular metabolism is demonstrated by the marked brain and systemic organ abnormalities occuring in peroxisome biogenesis disorders and peroxisomal enzyme deficiencies. " 11/01/2018 - "The importance of peroxisomal metabolism is illustrated by severe peroxisome biogenesis disorders in which functional peroxisomes are absent or disorders caused by single peroxisomal enzyme deficiencies. " 08/01/2018 - "These disorders can be broadly classified into 2 main groups; peroxisome biogenesis disorders (PBDs) and single peroxisomal enzyme deficiencies. " 01/01/2018 - "This depends largely on intact peroxisomal β-oxidation given the similarities in pathologies between peroxisome biogenesis disorders and deficiency of multifunctional protein-2 (MFP2), the central enzyme of this pathway. " 01/01/2013 - "The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. "
6.	PeroxinsIBA 11/01/2022 - "Investigations into peroxisome biogenesis and the human peroxisome biogenesis disorders (PBDs) have identified 14 PEX genes encoding peroxins involved in peroxisome biogenesis and the mutation of PEX genes is responsible for the PBDs. " 01/01/2019 - "Effects of peroxin gene mutations on mitochondrion-dependent apoptosis may contribute to pathogenesis of peroxisome biogenesis disorders.This" 01/01/2012 - "PEX26 responsible for peroxisome biogenesis disorders of complementation group 8 codes for C-tail-anchored type-II membrane peroxin Pex26p, the recruiter of Pex1p-Pex6p complexes to peroxisomes. " 09/01/2011 - "Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. " 09/22/2006 - "Two AAA peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for peroxisome biogenesis disorders of complementation group 1 (CG1) and CG4, respectively. "
7.	LipidsIBA 06/01/2007 - "Changes in the molecular species of lipids associated with Pex2 gene-mutation were investigated to elucidate the pathogeneses of peroxisome biogenesis disorders. " 01/01/2004 - "We investigated lipid composition and FA metabolism in Chinese hamster ovary CHO-K1) cells and Pex5-mutated CHO-K1 (ZP102) cells to clarify the biochemical bases of peroxisome biogenesis disorders (PBD). " 11/01/2015 - "In this review, we cover all aspects of cerebellar pathology that were reported in peroxisome biogenesis disorders and in diseases caused by dysfunction of the peroxisomal α-oxidation, β-oxidation or ether lipid synthesis pathways. " 05/01/2010 - "We conclude that the combined defect of peroxisomal beta-oxidation and ether lipid synthesis does not solely account for the typical cortical neuronal migration defect of mice with peroxisome biogenesis disorders but contributes to their hypotonia." 11/16/2018 - "Despite the versatile metabolic functions of peroxisomes such as lipid synthesis and fatty acid oxidation and their relevance to genetically inherited diseases, namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there is not much research on peroxisome-targeting therapeutics. "
8.	Membrane Proteins (Integral Membrane Proteins)IBA 06/01/2005 - "Matsumoto and colleagues recently identified PEX26 as the gene responsible for complementation group 8 of the peroxisome biogenesis disorders and showed that it encodes an integral peroxisomal membrane protein with a single C-terminal transmembrane domain and a cytosolic N-terminus that interacts with the PEX1/PEX6 heterodimer through direct binding to the latter. " 08/18/2000 - "The three peroxin genes, PEX12, PEX2, and PEX10, encode peroxisomal integral membrane proteins with RING finger at the C-terminal part and are responsible for human peroxisome biogenesis disorders. " 08/23/1996 - "The peroxisomal integral membrane protein Pay5p is a homologue of mammalian PAF-1 proteins, which are essential for peroxisome assembly and whose mutation in humans results in peroxisome biogenesis disorders. " 08/01/2004 - "Peroxisome biogenesis disorders result from defects in peroxin proteins involved in peroxisomal matrix and membrane protein import. "
9.	Biomarkers (Surrogate Marker)IBA 01/01/2003 - "Biochemical markers predicting survival in peroxisome biogenesis disorders." 12/10/2002 - "Biochemical markers predicting survival in peroxisome biogenesis disorders." 11/01/2023 - "Dicarboxylic acylcarnitine biomarkers in peroxisome biogenesis disorders."
10.	Peroxisomal Targeting SignalsIBA 08/01/1998 - "Mutations in the peroxisome targeting signal (PTS) 1 receptor gene, PEX5 , are responsible for complementation group (CG) 2 of the peroxisome biogenesis disorders (PBD). " 08/27/1999 - "To investigate mechanisms related to functions of the peroxisome targeting signal (PTS) 1 receptor, Pex5p, we analyzed peroxisome matrix protein import in fibroblasts from three patients with peroxisome biogenesis disorders, all with different mutations in the PEX5 gene. " 01/01/2022 - ": ABCD3/PMP70: ATP binding cassette subfamily D member 3; ACOX1: acyl-CoA oxidase 1; AP: autophagosome; COX: cytochrome c oxidase; CQ: chloroquine; CRISPRi: clustered regularly interspaced short palindromic repeats interference; DLBCL: diffuse large B-cell lymphoma; GO: gene ontology; dCas9: Cas9 endonuclease dead, or dead Cas9; HDACi: histone deacetylase inhibitors; IHC: Immunohistochemistry; LAMP2: lysosomal associated membrane protein 2; LCFAs: long-chain fatty acids; LFQ-MS: label-free quantitation mass spectrometry; LPC: lysophoshatidylcholine; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PBD: peroxisome biogenesis disorders; PTS1: peroxisomal targeting signal 1; ROS: reactive oxygen species; sgRNA: single guide RNA; VLCFAs: very-long chain fatty acids; Vor: vorinostat; WO: wash-off."

Therapies and Procedures

1.

Therapeutics 10/01/2014 - "These findings may lead to a new approach to Pex7p-based therapies for the treatment of peroxisome biogenesis disorders such as RCDP." 12/10/2021 - "These proof-of-concept studies represent the first application of gene augmentation therapy to treat peroxisome biogenesis disorders and support the potential for retinal gene delivery to improve vision in these patients." 11/01/2010 - "Peroxin 5 has medical significance in that (i) congenital defects can lead to fatal peroxisome biogenesis disorders, (ii) inefficient peroxisome targeting is linked to disease and aging and (iii) differences between human peroxin 5 and homologues in pathogens may be exploited in the development of therapeutics." 11/16/2018 - "Despite the versatile metabolic functions of peroxisomes such as lipid synthesis and fatty acid oxidation and their relevance to genetically inherited diseases, namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there is not much research on peroxisome-targeting therapeutics. "