scholarly journals PEX6: An Imaging Overlap Between Peroxisomal and Lysosomal Storage Diseases

2020 ◽  
Vol 2 (2) ◽  
pp. 28-32
Author(s):  
César Augusto Pinheiro Ferreira Alves ◽  
Luisa Norbert Simonsen ◽  
Jonathan Rodrigues ◽  
Isabella Peixoto de Barcelos ◽  
Clarissa Bueno ◽  
...  
Keyword(s):  
Zellweger Syndrome ◽  
Krabbe Disease ◽  
Chondrodysplasia Punctata ◽  
Imaging Features ◽  
Peroxisome Biogenesis ◽  
Lysosomal Storage ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Pathogenic Variants ◽  
Craniofacial Dysmorphism

Peroxisomal disorders are a group of expanding genetic diseases divided into two major categories: peroxisome biogenesis defects (Zellweger spectrum disorder), and single enzymatic defects. Disorders of Peroxisome Biogenesis occur when there are biallelic pathogenic variants in any of the 13 PEX genes, which code for the peroxins, proteins required for peroxisome biogenesis. This group of disorders includes two distinct phenotypes: Rhizomelic Chondrodysplasia Punctata Type-1 and Zellweger Spectrum Disorders (ZSD), of which Zellweger syndrome is the most severe, neonatal adrenoleukodystrophy is intermediate, and infantile Refsum is the mildest. The spectrum’s most frequent defects are observed in the proteins PEX1 and PEX6, and the most common clinical presentation is Zellweger spectrum, which is often associated with craniofacial dysmorphism with neurologic abnormalities. Typically, the neuroimaging pattern shows several malformative features, including a range of cortical gyral abnormalities such as microgyria and pachygyria, and impairment of the myelination. Nevertheless, we report two siblings with peroxisomal disorder, with unexpected leukodystrophy pattern of the brain mimicking lysosomal storage disease, with classical imaging features of Krabbe disease on brain magnetic resonance image. By whole exome sequencing, we identified two pathogenic variants in compound heterozygosity in PEX6: Chr6:42.933.455 C>T (c.2435G>A), and Chr6:42.935.188 C>T (c.1802G>A). Thus, a final diagnosis of peroxisome disorder was confirmed. The index cases highlight the importance of considering peroxisome disorders as a differential diagnosis for patients with imaging features that resemble Krabbe disease.

Diagnosis of peroxisomal disorders by analysis of phytanic and pristanic acids in stored blood spots collected at neonatal screening

1993 ◽  
Vol 39 (9) ◽  
pp. 1904-1906 ◽  
Author(s):  
H J ten Brink ◽  
C M van den Heuvel ◽  
E Christensen ◽  
C Largillière ◽  
C Jakobs
Keyword(s):  
Neonatal Screening ◽  
Phytanic Acid ◽  
Zellweger Syndrome ◽  
Dried Blood Spots ◽  
Chondrodysplasia Punctata ◽  
Pristanic Acid ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Blood Spots ◽  
Blood Spot

Abstract Concentrations of phytanic acid and pristanic acid were measured in stored dried blood spots collected at neonatal screening from patients with peroxisomal disorders, and compared with concentrations in control blood spots. In blood spots from two patients with Zellweger syndrome both phytanic acid and pristanic acid concentrations were increased but their concentration ratio was normal. In the blood spot from a patient with rhizomelic chondrodysplasia punctata, the concentration of phytanic acid was increased, whereas pristanic acid was within the control range, resulting in a low pristanic acid/phytanic acid ratio. In the blood spot from a patient with X-linked adrenoleukodystrophy, the concentrations of the acids and their ratio were normal. These findings are consistent with results for these acids in plasma from such patients. Measurement of phytanic acid and pristanic acid and their ratios in stored dried blood collected at neonatal screening can therefore be used in the diagnosis of peroxisomal disorders, especially for those cases in which, owing to early death of the patient, no other material is available for biochemical investigations.

scholarly journals Defective lipid remodeling of GPI anchors in peroxisomal disorders, Zellweger syndrome, and rhizomelic chondrodysplasia punctata

2012 ◽  
Vol 53 (4) ◽  
pp. 653-663 ◽  
Author(s):  
Noriyuki Kanzawa ◽  
Nobuyuki Shimozawa ◽  
Ronald J. A. Wanders ◽  
Kazutaka Ikeda ◽  
Yoshiko Murakami ◽  
...  
Keyword(s):  
Zellweger Syndrome ◽  
Chondrodysplasia Punctata ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders

Profiles of very-long-chain fatty acids in plasma, fibroblasts, and blood cells in Zellweger syndrome, X-linked adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata

1993 ◽  
Vol 39 (8) ◽  
pp. 1632-1637 ◽  
Author(s):  
R B Schutgens ◽  
I W Bouman ◽  
A A Nijenhuis ◽  
R J Wanders ◽  
M E Frumau
Keyword(s):  
Fatty Acids ◽  
Blood Cells ◽  
Zellweger Syndrome ◽  
Syndrome X ◽  
Chondrodysplasia Punctata ◽  
Long Chain Fatty Acids ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Profiles of saturated very-long-chain (> C22) fatty acids were studied in plasma, fibroblasts, erythrocytes, platelets, and leukocytes of patients affected by peroxisomal disorders such as Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD), and classic rhizomelic chondrodysplasia punctata (RCDP) and in controls. In Zellweger patients, the concentration of hexacosanoic acid (C26:0) and the C26:0/C22:0 ratio are greatly increased in plasma and fibroblasts. However, the plasma concentration of docosanoic acid (C22:0) is greatly decreased. Also in platelets, leukocytes, and to a lesser extent erythrocytes, the C26:0 concentrations and both the C26:0/C22:0 and C24:0/C22:0 ratios are greatly increased. The C24:0/C22:0 ratio is significantly increased in plasma, platelets, and leukocytes, but not in erythrocytes. In X-ALD, the C26:0 concentration and the C26:0/C22:0 and C24:0/C22:0 ratios are significantly increased in plasma, fibroblasts, platelets, and leukocytes, but the erythrocytes show substantial overlap in the 5-90% ranges between controls and patients. In RCDP, slightly increased C26:0 and C26:0/C22:0 ratios are found in erythrocytes, platelets, and leukocytes, but not in plasma and fibroblasts. We conclude that plasma and fibroblasts are the specimens of choice for biochemical diagnosis of Zellweger syndrome and X-ALD, respectively. The slight increase in C26:0 in blood cells of RCDP patients suggests a decreased flux of very-long-chain fatty acids through the peroxisomal beta-oxidation pathway in liver in this genetic disorder.

Peroxisomal Disorders: Experience from a Genetic Center in North India

2018 ◽  
Vol 17 (02) ◽  
pp. 065-070
Author(s):  
Suresh Kumar Angurana ◽  
Renu Suthar ◽  
Inusha Panigrahi
Keyword(s):  
Fatty Acids ◽  
North India ◽  
Chondrodysplasia Punctata ◽  
Long Chain Fatty Acids ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Clinical Profiles ◽  
Characteristic Features ◽  
Biochemical Features ◽  
Long Chain

AbstractDiagnosis of peroxisomal disorders (PDs) is often delayed because of unfamiliarity with the characteristic features of PDs and their genetic heterogeneity. Aim of this study was to describe clinical profiles of six children with PDs. This is a retrospective study involving six children with PDs. The patients included three males, one female, and a fetus. Three patients were diagnosed with Zellweger's syndrome, two with rhizomelic chondrodysplasia punctata, and one with X-linked adrenoleukodystrophy. These diagnoses were established based on clinical, radiological, and biochemical features (elevated very long chain fatty acids levels). Parents of all cases have been provided genetic counseling and advised of prenatal diagnosis. Diagnosis of PDs requires knowledge of characteristic clinicoradiological features, and clinical confirmation is possible with simple imaging and biochemical investigations. Molecular diagnosis is possible for selected cases.

scholarly journals Pex18p and Pex21p, a Novel Pair of Related Peroxins Essential for Peroxisomal Targeting by the PTS2 Pathway

1998 ◽  
Vol 143 (7) ◽  
pp. 1859-1869 ◽  
Author(s):  
P. Edward Purdue ◽  
Xudong Yang ◽  
Paul B. Lazarow
Keyword(s):  
Subcellular Localization ◽  
Protein Targeting ◽  
Chondrodysplasia Punctata ◽  
Peroxisome Biogenesis ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Biogenesis ◽  
Peroxisomal Targeting ◽  
Two Hybrid ◽  
Import Receptor

We have identified ScPex18p and ScPex21p, two novel S. cerevisiae peroxins required for protein targeting via the PTS2 branch of peroxisomal biogenesis. Targeting by this pathway is known to involve the interaction of oligopeptide PTS2 signals with Pex7p, the PTS2 receptor. Pex7p function is conserved between yeasts and humans, with defects in the human protein causing rhizomelic chondrodysplasia punctata (RCDP), a severe, lethal peroxisome biogenesis disorder characterized by aberrant targeting of several PTS2 peroxisomal proteins, but uncertainty remains about the subcellular localization of this receptor. Previously, we have reported that ScPex7p resides predominantly in the peroxisomal matrix, suggesting that it may function as a highly unusual intraorganellar import receptor, and the data presented in this paper identify Pex18p and Pex21p as key components in the targeting of Pex7p to peroxisomes. They each interact specifically with Pex7p both in two-hybrid analyses and in vitro. In cells lacking both Pex18p and Pex21p, Pex7p remains cytosolic and PTS2 targeting is completely abolished. Pex18p and Pex21p are weakly homologous to each other and display partial functional redundancy, indicating that they constitute a two-member peroxin family specifically required for Pex7p and PTS2 targeting.

scholarly journals Molecular diagnostics of the Krabbe disease in Russian children

2020 ◽  
Vol 1 (1) ◽  
pp. 21-28
Author(s):  
Alexander A. Pushkov ◽  
Nataliya N. Mazanova ◽  
Lyudmila M. Kuzenkova ◽  
Nataliya V. Zhurkova ◽  
Oksana V. Globa ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Molecular Diagnostics ◽  
High Efficiency ◽  
Molecular Genetic ◽  
Krabbe Disease ◽  
Control Group ◽  
Laboratory Diagnostics ◽  
Lysosomal Storage ◽  
Pathogenic Variants ◽  
Galc Gene

Introduction. Krabbe disease (KD) is the lysosomal storage disease developed due to the decline of the galactocerebrosidase activity associated with mutations in the GALC gene. It leads to the development of oligodendrocytes and lemmocytes (Schwann cells) myelin-forming dysfunction. Nowadays the only possible treatment of KD is hemopoietic cell transplantation which should be performed before the manifestation of any signs of disease. That is why laboratory diagnostics has special significance. The aim of the study. To elaborate the algorithm of a molecular diagnostics of the Krabbe disease (KD) in Russian children. Material and methods. 190 patients were diagnosed for the exclusion of KD during the period from 2012 to 2019. In all cases, there was measured a galactocerebrosidase activity in dry blood spots. In cases with the declined enzyme activity, there was performed a further search of pathogenic variants in the GALC gene. The concentration of glycosyl sphingosine (Lyso-GL1) biomarker was measured in 90 patients included in the study since 2016. Results. The enzyme activity was decreased in all patients in comparison with the control group (0.330.05; 2.950.24 mol/l/h, (p0.001; CI: 95%) in 9 patients. Also, we revealed an increased concentration of Lyso-GL1 biomarker in matched controls (12.501.57 ng/ml; 1.80.33 ng/ml, (p0.005; CI: 95%) in 5 patients. During molecular genetic testing of KD, three novel pathogenic variants of the GALC gene were revealed in 3 out of 9 patients: c.265-2AG, c.1036del and c.2037_2040del. Conclusion. The Lyso-GL1 concentration measurement can be used as an additional diagnostics method of KD. The high efficiency of the presented algorithm for the KD diagnostics in Russian children is presented.

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