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Proceedings of the Japan Academy.... 2016Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very... (Review)
Review
Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Humans; Peroxisomal Disorders; Peroxisomes
PubMed: 27941306
DOI: 10.2183/pjab.92.463 -
Biochemical and Biophysical Research... May 2018Mitochondria are constantly communicating with the rest of the cell. Defects in mitochondria underlie severe pathologies, whose mechanisms remain poorly understood. It... (Review)
Review
Mitochondria are constantly communicating with the rest of the cell. Defects in mitochondria underlie severe pathologies, whose mechanisms remain poorly understood. It is becoming increasingly evident that mitochondrial malfunction resonates in other organelles, perturbing their function and their biogenesis. In this manuscript, we review the current knowledge on the cross-talk between mitochondria and other organelles, particularly lysosomes, peroxisomes and the endoplasmic reticulum. Several organelle interactions are mediated by transcriptional programs, and other signaling mechanisms are likely mediating organelle dysfunction downstream of mitochondrial impairments. Many of these organelle crosstalk pathways are likely to have a role in pathological processes.
Topics: AMP-Activated Protein Kinases; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Endoplasmic Reticulum; Gene Expression Regulation; Humans; Lysosomal Storage Diseases; Lysosomes; Mitochondria; Mitochondrial Diseases; Peroxisomes; Signal Transduction; Transcription, Genetic; Zellweger Syndrome
PubMed: 28456629
DOI: 10.1016/j.bbrc.2017.04.124 -
JNMA; Journal of the Nepal Medical... Feb 2024Zellweger syndrome is an autosomal recessive disease within the spectrum of peroxisome biogenesis disorder manifesting in the neonatal period with profound dysfunction...
UNLABELLED
Zellweger syndrome is an autosomal recessive disease within the spectrum of peroxisome biogenesis disorder manifesting in the neonatal period with profound dysfunction of the central nervous system, liver and kidney. Common clinical presentations include hypotonia, seizure, hepatomegaly, craniofacial dysmorphism and early death. Mutation in one of the PEX genes coding for a peroxisome assembly protein creates a functionally incompetent organelle causing accumulation of very long chain fatty acids in various organs. Here we report the case of a 5-month-old male presented at birth with hypotonia, poor feeding, gross congenital anomalies and later during early infancy with failure to thrive, several episodes of seizures, aspiration due to feeding difficulties and recurrent severe pneumonia. A whole genomic sequencing brought us to the final diagnosis of Zellweger syndrome. Despite an absence of treatment options, prompt diagnosis of Zellweger syndrome is important for providing appropriate symptomatic care, definitive genetic testing and prenatal counselling.
KEYWORDS
case reports; mutation; neonate; Zellweger syndrome.
Topics: Infant, Newborn; Humans; Male; Infant; Zellweger Syndrome; Muscle Hypotonia; Peroxisomal Disorders; Genetic Testing; Mutation
PubMed: 38409970
DOI: 10.31729/jnma.8467 -
Pediatrics and Neonatology Dec 2017Zellweger syndrome (ZS) is a peroxisome biogenesis disorder attributed to a mutation of the PEX genes family. The incidence of this disease in Africa and the Arab world...
BACKGROUND
Zellweger syndrome (ZS) is a peroxisome biogenesis disorder attributed to a mutation of the PEX genes family. The incidence of this disease in Africa and the Arab world remains unknown. This contribution is aimed at describing the clinical phenotype and biochemical features in Tunisian patients with ZS in order to improve the detection and management of this severe disorder.
METHODS
A total of 52 patients diagnosed with ZS and 60 age- and sex-matched healthy controls were included in this study. Patients were recruited during the past 21 years, and the diagnosis of ZS was based on clinical and biochemical characteristics. Plasma very long chain fatty acids (VLCFA) were analyzed using capillary gas chromatography. The estimated incidence of ZS was calculated using the Hardy-Weinberg formula.
RESULTS
The estimated incidence of ZS is 1/15,898 in Tunisia. Age at diagnosis varied between 3 days and 18 months. Severe neurological syndrome, polymalformative features, and hepatodigestive signs were observed in 100%, 67.9%, and 32% of patients, respectively. Values for plasma C26:0 and C26:0/C22:0 and C24:0/C22:0 ratios were noticeably higher in ZS patients than in controls. Distributions of values were completely different for C26:0 (0.10-0.37 vs. 0.001-0.009), C26:0/C22:0 ratio (0.11-1.29 vs. 0.003-0.090), and C24:0/C22:0 ratio (1.03-3.18 vs. 0.4-0.90) in ZS patients versus controls, respectively.
CONCLUSIONS
This study highlights the high incidence of ZS in Tunisia and the possibility of simple and reliable biochemical diagnosis, thus permitting early genetic counseling for families at risk.
Topics: Fatty Acids; Female; Genetic Counseling; Humans; Infant; Infant, Newborn; Male; Tunisia; Zellweger Syndrome
PubMed: 28330580
DOI: 10.1016/j.pedneo.2016.08.011 -
International Journal of Molecular... Aug 2019Peroxisome biogenesis disorders (PBDs) are nontreatable hereditary diseases with a broad range of severity. Approximately 65% of patients are affected by mutations in... (Review)
Review
Peroxisome biogenesis disorders (PBDs) are nontreatable hereditary diseases with a broad range of severity. Approximately 65% of patients are affected by mutations in the peroxins Pex1 and Pex6. The proteins form the heteromeric Pex1/Pex6 complex, which is important for protein import into peroxisomes. To date, no structural data are available for this AAA+ ATPase complex. However, a wealth of information can be transferred from low-resolution structures of the yeast Pex1/Pex6 complex and homologous, well-characterized AAA+ ATPases. We review the abundant records of missense mutations described in PBD patients with the aim to classify and rationalize them by mapping them onto a homology model of the human Pex1/Pex6 complex. Several mutations concern functionally conserved residues that are implied in ATP hydrolysis and substrate processing. Contrary to fold destabilizing mutations, patients suffering from function-impairing mutations may not benefit from stabilizing agents, which have been reported as potential therapeutics for PBD patients.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphate; Amino Acid Sequence; Animals; Humans; Membrane Proteins; Models, Molecular; Mutation, Missense; Peroxisomal Disorders; Protein Conformation; Protein Interaction Maps; Sequence Alignment
PubMed: 31374812
DOI: 10.3390/ijms20153756 -
AJNR. American Journal of Neuroradiology 1997To determine characteristic MR imaging features of Zellweger syndrome.
PURPOSE
To determine characteristic MR imaging features of Zellweger syndrome.
METHODS
Clinical records, laboratory records, and MR studies of six patients with Zellweger syndrome were reviewed retrospectively. MR studies were examined for the state of myelination; the presence, extent, and morphologic appearance of cerebral cortical anomalies; the status of the cerebellar cortex, basal nuclei, and brain stem; and the presence or absence of any regions of abnormal signal intensity.
RESULTS
The diagnosis of Zellweger syndrome was established in all patients by clinical findings combined with laboratory and MR results. All patients had impaired myelination and diffusely abnormal cortical gyral patterns that consisted of regions of microgyria (primarily in the frontal and perisylvian cortex) together with regions of thickened pachygyric cortex (primarily perirolandic and occipital). The pachygyric regions were in the form of deep cortical infoldings. Germinolytic cysts were visible in the caudothalamic groove in all patients, seen best on coronal or sagittal T1-weighted images. One patient had T1 shortening in the bilateral globus pallidus, presumably related to hepatic dysfunction and hyperbilirubinemia.
CONCLUSION
The combination of hypomyelination, cortical malformations that are most severe in the perisylvian and perirolandic regions, and germinolytic cysts are highly suggestive of Zellweger syndrome in the proper clinical setting.
Topics: Basal Ganglia; Brain Stem; Cerebellar Cortex; Cerebral Cortex; Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Retrospective Studies; Sensitivity and Specificity; Zellweger Syndrome
PubMed: 9194444
DOI: No ID Found -
Children (Basel, Switzerland) Oct 2023The goal of this manuscript is to present and summarize several rare pediatric syndromes (Zellweger syndrome, Kartagener syndrome, Prader-Willi syndrome,... (Review)
Review
The goal of this manuscript is to present and summarize several rare pediatric syndromes (Zellweger syndrome, Kartagener syndrome, Prader-Willi syndrome, Schinzel-Giedion syndrome, Fanconi anemia, Joubert-Boltshauser syndrome, Poretti-Boltshauser syndrome, and Langer-Giedion syndrome) who have been named after luminary "Swiss" physicians (pediatricians, pediatric neurologists, or pediatric radiologists) who recognized, studied, and published these syndromes. In this manuscript, a brief historical summary of the physicians is combined with the key clinical symptoms at presentation and the typical imaging findings. This manuscript is not aiming to give a complete comprehensive summary of the syndromes, nor does it ignore the valuable contributions of many "Swiss" scientists who are not included here, but focuses on several rare syndromes that benefit from imaging data.
PubMed: 37892331
DOI: 10.3390/children10101668 -
Orphanet Journal of Rare Diseases Dec 2015Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a... (Review)
Review
Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focuses on the management of patients with a ZSD and provides recommendations for supportive therapeutic options for all those involved in the care for ZSD patients.
Topics: Disease Management; Humans; Mutation; Peroxisomes; Zellweger Syndrome
PubMed: 26627182
DOI: 10.1186/s13023-015-0368-9 -
Translational Pediatrics Jul 2021Zellweger syndrome (ZS) is commonly manifested as facial deformities, hypotonia, and liver dysfunction. However, ZS caused by gene mutation shows a broad and dispersed...
BACKGROUND
Zellweger syndrome (ZS) is commonly manifested as facial deformities, hypotonia, and liver dysfunction. However, ZS caused by gene mutation shows a broad and dispersed clinical pattern. In this study, the gene in ZS was analyzed to enrich its clinical characteristics. Meanwhile, phenotypic and genotypic characteristics of Zellweger spectrum disorder (ZSD) induced by mutation were evaluated.
METHODS
The clinical data of newborn with ZS in our hospital were analyzed retrospectively. We performed WES and found that the infant carried the gene variant. We searched the biomedical literature databases (PubMed, Web of Science, and EMBASE) to compare clinical features and genotypes.
RESULTS
The neonate developed facial deformities, hypotonia, feeding difficulties, and seizures. Her homozygous variant was found in the gene (NM_017929: exon2: c.34del) inherited from both parents. Electronic databases, including our case, reported 32 pathogenic variants in . We found that variation c.292C> T accounted for the largest proportion of mutations (16/66, 24.24%). The proportion of deleterious mutations in ZS patients was significantly higher than that in NALD and IRD patients.
CONCLUSIONS
We identified pathogenic variations in the gene and expanded the known mutant spectrum. By comparing patients with mutations, the study determined that a significantly higher percentage of deleterious mutations in ZS was associated with severe clinical phenotypic characteristics.
PubMed: 34430430
DOI: 10.21037/tp-21-103 -
International Journal of Pediatrics &... Dec 2019
PubMed: 31890844
DOI: 10.1016/j.ijpam.2019.11.002