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Cellular and Molecular Life Sciences :... Jun 2002Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous metabolic processes, both catabolic and... (Review)
Review
Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous metabolic processes, both catabolic and anabolic, including beta-oxidation of very long chain fatty acids, metabolism of hydrogen peroxide, plasmalogen biosynthesis and bile acid synthesis. In several genetic diseases, there is either isolated deficiency of a specific peroxisomal protein (single-protein deficiencies) or a defect in the formation of the organelle with loss of multiple peroxisomal functions (peroxisome biogenesis disorders). X-linked adrenoleukodystrophy is an example of the former, and the Zellweger spectrum of the latter. Peroxisome biogenesis disorders are inherited in an autosomal recessive manner and result from mutations in any of at least 12 PEX genes that encode peroxins. This article reviews the peroxisomal system, the clinical, biochemical and molecular aspects of peroxisomal disorders, and discusses recent scientific advances in the understanding of peroxisome biogenesis.
Topics: Humans; Peroxisomal Disorders; Peroxisomes; Zellweger Syndrome
PubMed: 12169017
DOI: 10.1007/s00018-002-8486-7 -
Indian Pediatrics Feb 1997
Topics: Facies; Fatal Outcome; Female; Humans; Infant; Infant, Newborn; Pregnancy; Prenatal Diagnosis; Zellweger Syndrome
PubMed: 9255013
DOI: No ID Found -
Journal of Applied Genetics Feb 2020Zellweger spectrum disorders (ZSD) constitute a group of rare autosomal recessive disorders characterized by a defect in peroxisome biogenesis due to mutations in one of...
Zellweger spectrum disorders (ZSD) constitute a group of rare autosomal recessive disorders characterized by a defect in peroxisome biogenesis due to mutations in one of 13 PEX genes. The broad clinical heterogeneity especially in late-onset presenting patients and a mild phenotype complicates and delays the diagnostic process. Here, we report a case of mild ZSD, due to novel PEX1 variants. The patient presented with an early hearing loss, bilateral cataracts, and leukodystrophy on magnetic resonance (MR) images. Normal results of serum very-long-chain fatty acids (VLCFA) and phytanic acid were found. Molecular diagnostics were performed to uncover the etiology of the clinical phenotype. Using whole exome sequencing, there have been found two variants in the PEX1 gene-c.3450T>A (p.Cys1150*) and c.1769T>C (p.Leu590Pro). VLCFA measurement in skin fibroblasts and C26:0-lysoPC in dried blood spot therefore was performed. Both results were in line with the diagnosis of ZSD. To conclude, normal results of routine serum VLCFA and branched-chain fatty acid measurement do not exclude mild forms of ZSD. The investigation of C26:0-lysoPC should be included in the diagnostic work-up in patients with cataract, hearing loss, and leukodystrophy on MR images suspected to suffer from ZSD.
Topics: ATPases Associated with Diverse Cellular Activities; Adolescent; Biomarkers; Brain; Child; Child, Preschool; DNA Mutational Analysis; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Infant; Magnetic Resonance Imaging; Male; Membrane Proteins; Phenotype; Severity of Illness Index; Symptom Assessment; Young Adult; Zellweger Syndrome
PubMed: 31628608
DOI: 10.1007/s13353-019-00523-w -
Metabolic, Pediatric, and Systemic... 1989Progresses in biochemistry permit one to distinguish three biochemical forms of Zellweger Syndrome: 1) hyperpipecolic acidemia, 2) neonatal adrenoleukodystrophy, and 3)...
Progresses in biochemistry permit one to distinguish three biochemical forms of Zellweger Syndrome: 1) hyperpipecolic acidemia, 2) neonatal adrenoleukodystrophy, and 3) infantile Refsum's disease, which have similar clinical manifestations. A seven-month-old male patient with Zellweger Syndrome is presented. He had absence of peroxismes in the liver and elevated pipecolic acids and abnormal levels of bile acids in the blood. The child had a typical neurologic clinical manifestation with hepatomegaly. The ophthalmoscopy revealed grey disks and retinitis pigmentosa with extinguished ERG and law and delayed VEP. The importance of the constant retinal involvement in Zellweger Syndrome is discussed.
Topics: Bile Acids and Salts; Electroretinography; Fundus Oculi; Humans; Infant; Male; Pipecolic Acids; Retinitis Pigmentosa; Zellweger Syndrome
PubMed: 2628705
DOI: No ID Found -
Progress in Clinical and Biological... 1990
Review
Topics: Adrenoleukodystrophy; Diffuse Cerebral Sclerosis of Schilder; Humans; Microbodies; Zellweger Syndrome
PubMed: 2183241
DOI: No ID Found -
Postepy Biochemii Dec 2018Peroxisomes are multifunctional microorganelles that play a key role in numerous biochemical processes adapting dynamically to the current physiological requirements of... (Review)
Review
Peroxisomes are multifunctional microorganelles that play a key role in numerous biochemical processes adapting dynamically to the current physiological requirements of the cell. The disturbance of the peroxisome structure due to mutations in different PEX and non-PEX genes coding functional peroxisomal proteins is the pathogenic basis of the peroxisomal disorders. The β-oxidation process of very long-chain fatty acids (VLCFA) is a unique metabolic pathway located exclusively in the peroxisome. This determines that VLCFA is the main biomarker for the diagnosis of peroxisomal diseases. Peroxisomal disorders present a broad spectrum of clinical symptoms from the neonatal, severe Zellweger syndrome with dysmorphia, multi-organ dysfunction to the late symptomatic adult form of X-linked adrenoleukodystrophy. Relatively common the use of highly specialized analytical techniques causes it is a still growing group of rare metabolic diseases.
Topics: Adrenoleukodystrophy; Fatty Acids; Humans; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes; Zellweger Syndrome
PubMed: 30656921
DOI: 10.18388/pb.2018_150 -
The Japanese Journal of Human Genetics Mar 19971. A human peroxisome assembly factor-1 (PAF-1) complementary DNA has been cloned that restores the morphological and biochemical abnormalities (including defective... (Review)
Review
1. A human peroxisome assembly factor-1 (PAF-1) complementary DNA has been cloned that restores the morphological and biochemical abnormalities (including defective peroxisome assembly) in fibroblasts from a patient with group F Zellweger syndrome. The cause of the syndrome in this patient was a point mutation that resulted in the premature termination of PAF-1. The homozygous patient apparently inherited the mutation from her parents, each of whom was heterozygous for that mutation. Furthermore, we cloned and characterized the rat and human cDNAs for peroxisome-assembly factor-2 (PAF-2), which restores peroxisomes of the complementary group C Zellweger cells, by functional complementation, and identified two pathogenic mutations in the PAF-2 gene in two patients. 2. Seventeen mutations have been identified in 13 mitochondrial acetoacetyl-CoA thiolase-deficient patients. 3. We purified N-acetylgalactosamine-6-sulfate (GalNAc6S) sulfatase and cloned the full-length cDNA of human N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The gene encoding GalNAc6S sulfatase has been localized by fluorescence in situ hybridization to chromosome 16q24, and the entire genomic gene structure has been characterized. About 40 different GALNS gene mutations have been identified in the patients with mucopolysaccharidosis IV A.
Topics: Acetyl-CoA C-Acyltransferase; Animals; Chromosome Mapping; Cloning, Molecular; Humans; Mucopolysaccharidoses; Rats; Zellweger Syndrome
PubMed: 9183994
DOI: 10.1007/BF02766916 -
Archives of Pediatrics & Adolescent... Oct 1999
Review
Topics: Consanguinity; Humans; Infant; Prognosis; Zellweger Syndrome
PubMed: 10520622
DOI: 10.1001/archpedi.153.10.1105 -
BMJ Case Reports Apr 2016Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger...
Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterised by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. Increased levels of very long chain fatty acids are the biochemical hallmark and the most common mutations found in the PEX1 gene. We report an unusual presentation of Zellweger syndrome in a 2-month-old female infant with severe malnutrition, opportunistic infections, lymphopaenia and a small thymic shadow on chest radiography. With this clinical picture, an initial hypothesis of primary immunodeficiency was considered. It was later confirmed to not be the case. On follow-up, global developmental delay, bilateral optic nerve atrophy and moderate bilateral sensorineural deafness grade II were documented. There were no further infectious complications and we concluded malnutrition was the cause of the infant's immunocompromised state.
Topics: Female; Humans; Immunocompromised Host; Infant; Infant Nutrition Disorders; Lymphopenia; Opportunistic Infections; Zellweger Syndrome
PubMed: 27090541
DOI: 10.1136/bcr-2015-214283 -
The Neuroradiology Journal Oct 2017Zellweger syndrome, also referred to as cerebrohepatorenal syndrome, is a rare autosomal recessive disease representing the most severe form of the peroxisomal...
Zellweger syndrome, also referred to as cerebrohepatorenal syndrome, is a rare autosomal recessive disease representing the most severe form of the peroxisomal biogenesis disorders. Neuroanatomical sequelae include impaired neuronal migration, diffuse hypomyelination, and sensorineural degeneration. Due to the rare and severe nature of this disorder, early mortality, and comorbidities that place the patient at risk for sedated imaging, high-resolution magnetic resonance imaging findings of Zellweger syndrome are scarce in the literature. Presented here is a case of this rare disease imaged at 3.0 Tesla.
Topics: Fatal Outcome; Humans; Infant; Magnetic Resonance Imaging; Male; Retrospective Studies; Zellweger Syndrome
PubMed: 28452594
DOI: 10.1177/1971400917700670