4,204 results match your criteria Peroxisomal Disorders


Proteasome-dependent protein quality control of the peroxisomal membrane protein Pxa1p.

Biochim Biophys Acta Biomembr 2020 May 13;1862(9):183342. Epub 2020 May 13.

Department of Cell Biochemistry, University of Groningen, the Netherlands. Electronic address:

Peroxisomes are eukaryotic organelles that function in numerous metabolic pathways and defects in peroxisome function can cause serious developmental brain disorders such as adrenoleukodystrophy (ALD). Peroxisomal membrane proteins (PMPs) play a crucial role in regulating peroxisome function. Therefore, PMP homeostasis is vital for peroxisome function. Read More

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http://dx.doi.org/10.1016/j.bbamem.2020.183342DOI Listing

Genomic sequencing highlights the diverse molecular causes of Perrault syndrome: a peroxisomal disorder (PEX6), metabolic disorders (CLPP, GGPS1), and mtDNA maintenance/translation disorders (LARS2, TFAM).

Hum Genet 2020 May 12. Epub 2020 May 12.

Reproductive Development Group, Murdoch Children's Research Institute, Melbourne, Australia.

Perrault syndrome is a rare heterogeneous condition characterised by sensorineural hearing loss and premature ovarian insufficiency. Additional neuromuscular pathology is observed in some patients. There are six genes in which variants are known to cause Perrault syndrome; however, these explain only a minority of cases. Read More

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http://dx.doi.org/10.1007/s00439-020-02176-wDOI Listing

Recent insights into peroxisome biogenesis and associated diseases.

J Cell Sci 2020 May 11;133(9). Epub 2020 May 11.

Department of Chemical and Biological Science, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681, Japan.

Peroxisomes are single-membrane organelles present in eukaryotes. The functional importance of peroxisomes in humans is represented by peroxisome-deficient peroxisome biogenesis disorders (PBDs), including Zellweger syndrome. Defects in the genes that encode the 14 peroxins that are required for peroxisomal membrane assembly, matrix protein import and division have been identified in PBDs. Read More

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http://dx.doi.org/10.1242/jcs.236943DOI Listing

The Changing Face of Adrenoleukodystrophy.

Endocr Rev 2020 May 4. Epub 2020 May 4.

Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.

Adrenoleukodystrophy (ALD) is a rare X-linked disorder of peroxisomal oxidation due to mutations in ABCD1. It is a progressive condition with a variable clinical spectrum that includes primary adrenal insufficiency, myelopathy, and cerebral ALD. Adrenal insufficiency affects over 80% of ALD patients. Read More

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http://dx.doi.org/10.1210/endrev/bnaa013DOI Listing

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism.

Front Pharmacol 2020 24;11:351. Epub 2020 Mar 24.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

The dysregulation of hepatic lipid metabolism is one of the hallmarks in many liver diseases including alcoholic liver diseases (ALD) and non-alcoholic fatty liver diseases (NAFLD). Hepatic inflammation, lipoperoxidative stress as well as the imbalance between lipid availability and lipid disposal, are direct causes of liver steatosis. The application of herbal medicines with anti-oxidative stress and lipid-balancing properties has been extensively attempted as pharmaceutical intervention for liver disorders in experimental and clinical studies. Read More

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http://dx.doi.org/10.3389/fphar.2020.00351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105674PMC

Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.

Biochim Biophys Acta Mol Cell Res 2020 Jul 26;1867(7):118709. Epub 2020 Mar 26.

Biosciences, University of Exeter, Exeter, UK. Electronic address:

Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2020.118709DOI Listing

Severe phenotype of ATP6AP1-CDG in two siblings with a novel mutation leading to a differential tissue-specific ATP6AP1 protein pattern, cellular oxidative stress and hepatic copper accumulation.

J Inherit Metab Dis 2020 Mar 26. Epub 2020 Mar 26.

Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Congenital disorders of glycosylation (CDG) represent a wide range of >140 inherited metabolic diseases, continually expanding not only with regards to the number of newly identified causative genes, but also the heterogeneity of the clinical and molecular presentations within each subtype. The deficiency of ATP6AP1, an accessory subunit of the vacuolar H -ATPase, is a recently characterised N- and O-glycosylation defect manifesting with immunodeficiency, hepatopathy and cognitive impairment. At the cellular level, the latest studies demonstrate a complex disturbance of metabolomics involving peroxisomal function and lipid homeostasis in the patients. Read More

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http://dx.doi.org/10.1002/jimd.12237DOI Listing

Exome sequencing identifies mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment.

Mol Vis 2020 18;26:216-225. Epub 2020 Mar 18.

Centre for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.

Purpose: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration.

Methods: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing.

Results: The study allowed us to detect likely pathogenic variants in , a gene typically involved in peroxisomal biogenesis disorders (PBDs). Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090270PMC

Peroxisomal Dysfunction in Neurological Diseases and Brain Aging.

Front Cell Neurosci 2020 10;14:44. Epub 2020 Mar 10.

Department of Neurobiology and Anatomy, University of Texas McGovern Medical School, Houston, TX, United States.

Peroxisomes exist in most cells, where they participate in lipid metabolism, as well as scavenging the reactive oxygen species (ROS) that are produced as by-products of their metabolic functions. In certain tissues such as the liver and kidneys, peroxisomes have more specific roles, such as bile acid synthesis in the liver and steroidogenesis in the adrenal glands. In the brain, peroxisomes are critically involved in creating and maintaining the lipid content of cell membranes and the myelin sheath, highlighting their importance in the central nervous system (CNS). Read More

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http://dx.doi.org/10.3389/fncel.2020.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075811PMC

A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway.

J Biol Chem 2020 Apr 12;295(16):5321-5334. Epub 2020 Mar 12.

Division of Organelle Homeostasis, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Read More

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http://dx.doi.org/10.1074/jbc.RA119.011989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170515PMC

Earwax: A potentially useful medium to identify inborn errors of metabolism?

JIMD Rep 2020 Mar 14;52(1):72-78. Epub 2020 Feb 14.

Department of Chemical Pathology NIHR BRC Great Ormond Street Hospital Foundation Trust London UK.

Earwax was investigated as a source to identify patients' different inborn errors of metabolism (IEMs). Acylcarnitines, amino acids, and guanidino metabolites were measured from 28 treated patients with 11 different metabolic disorders including 3 organic acidaemias, 2 fatty acid oxidation defects, 6 amino acid disorders, and 1 peroxisomal abnormality. On the basis of the ratio of different acylcarnitine species relative to free carnitine, isovaleric acidaemia, methylmalonic acidaemia, and long-chain hydroxyacylCoA dehydrogenase deficiency could be discriminated from the other disorders. Read More

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http://dx.doi.org/10.1002/jmd2.12102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052688PMC

[Mechanism of action of cell therapy in hereditary diseases].

Medicina (B Aires) 2020 ;80 Suppl 2:2-6

Cátedra de Neurociencia Aplicada. Universidad Católica de Murcia (UCAM). Murcia, España. E-mail:

Inherited metabolism disorders are serious childhood diseases that lead to significant cognitive impairment and regression of psychomotor development. The pathophysiology of the neural progressive deterioration is usually associated with severe neuroinflammation and demyelination, and as a consequence, neurodegeneration. At the moment they have no adequate treatment and require early and aggressive therapeutic approaches, which entail high mortality rates and, very frequently, low degrees of functional improvement and survival. Read More

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Accurate and live peroxisome biogenesis evaluation achieved by lentiviral expression of a green fluorescent protein fused to a peroxisome targeting signal 1.

Histochem Cell Biol 2020 May 2;153(5):295-306. Epub 2020 Mar 2.

Laboratoire d'Hépatologie Pédiatrique et Thérapie Cellulaire, Unité PEDI, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), 1200, Brussels, Belgium.

Peroxisomes are ubiquitous organelles formed by peroxisome biogenesis (PB). During PB, peroxisomal matrix proteins harboring a peroxisome targeting signal (PTS) are imported inside peroxisomes by peroxins, encoded by PEX genes. Genetic alterations in PEX genes lead to a spectrum of incurable diseases called Zellweger spectrum disorders (ZSD). Read More

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http://dx.doi.org/10.1007/s00418-020-01855-zDOI Listing

Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation.

J Pediatr Endocrinol Metab 2020 Mar;33(3):437-441

Department of Pediatric Neurology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background Peroxisomal biogenesis disorders (PBDs) include a miscellaneous group of diseases which cause serious multisystem disease. Mutations of 13 different PEX genes lead to PBDs including Zellweger syndrome (ZS). Different types of mutations of PEX1 and PEX10 genes are correlated with broad-range phenotypes of PBDs. Read More

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http://dx.doi.org/10.1515/jpem-2019-0194DOI Listing

Fit-for-purpose biomarker LC-MS/MS qualification for the quantitation of very long chain fatty acids in human cerebrospinal fluid.

Bioanalysis 2020 Feb 13;12(3):143-158. Epub 2020 Feb 13.

Vertex Pharmaceuticals, Preclinical Safety Assessment - Bioanalysis, Boston, MA 02210, USA.

Very long chain fatty acids (VLCFAs) have been identified as biomarkers for several peroxisomal disorders necessitating the need for reliable biomarker assays in particular C, C, C, C in cerebrospinal fluid (CSF). Until now no absolute quantitation assay for total VLCFAs in CSF has been successfully developed and qualified for clinical use. A quantitative LC-MS/MS assay for total VLCFA in human CSF was developed. Read More

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http://dx.doi.org/10.4155/bio-2019-0256DOI Listing
February 2020

Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.

Autophagy 2020 Feb 12:1-17. Epub 2020 Feb 12.

Trauma Research Center, Fourth Medical Center of the Chinese PLA General Hospital, Beijing, People's Republic of China.

The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Read More

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http://dx.doi.org/10.1080/15548627.2020.1725377DOI Listing
February 2020

The Peroxisomal PTS1-Import Defect of - Deficient Cells Is Independent of Pexophagy in .

Int J Mol Sci 2020 Jan 29;21(3). Epub 2020 Jan 29.

Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Universitätsstr. 150, 44801 Bochum, Germany.

The important physiologic role of peroxisomes is shown by the occurrence of peroxisomal biogenesis disorders (PBDs) in humans. This spectrum of autosomal recessive metabolic disorders is characterized by defective peroxisome assembly and impaired peroxisomal functions. PBDs are caused by mutations in the peroxisomal biogenesis factors, which are required for the correct compartmentalization of peroxisomal matrix enzymes. Read More

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http://dx.doi.org/10.3390/ijms21030867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037794PMC
January 2020

Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina.

JAMA Netw Open 2020 Jan 3;3(1):e1920356. Epub 2020 Jan 3.

RTI International, Research Triangle Park, North Carolina.

Importance: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel.

Objective: To evaluate the performance of a single-tier newborn screening assay for X-ALD in North Carolina. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2019.20356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042889PMC
January 2020

X-Linked Adrenoleukodystrophy Mimicking Hereditary Spastic Paraplegia.

Mov Disord Clin Pract 2020 Jan 11;7(1):109-110. Epub 2019 Nov 11.

Department of Neurology, Ataxia Unit Universidade Federal de São Paulo São Paulo SP Brazil.

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http://dx.doi.org/10.1002/mdc3.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962678PMC
January 2020

Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes.

Turk J Pediatr 2019 ;61(2):289-291

Department of Pediatric Metabolism and Nutrition, Dr. Sami Ulus Maternity and Children's Training and Research Hospital, University of Health Sciences, Ankara, Turkey.

Gündüz M, Ünal Ö, Küçükçongar-Yavaş A, Kasapkara Ç. Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes. Turk J Pediatr 2019; 61: 289-291. Read More

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http://dx.doi.org/10.24953/turkjped.2019.02.023DOI Listing
January 2019

X-linked Adrenoleukodystrophy: Atypical Clinico-Radiological Presentation - Correspondence.

Authors:
J B Ghosh

Indian J Pediatr 2020 02 11;87(2):167-168. Epub 2020 Jan 11.

Department of Pediatrics, I.P.G.M.E.R & S.S.K.M Hospital, Kolkata, India.

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http://dx.doi.org/10.1007/s12098-019-03145-6DOI Listing
February 2020

Peroxisomal Disorders and Retinal Degeneration.

Adv Exp Med Biol 2019 ;1185:317-321

KU Leuven - University of Leuven, Department for Pharmaceutical and Pharmacological Sciences, Lab for Cell Metabolism, Leuven, Belgium.

Peroxisomal disorders are a group of inherited metabolic diseases, which can be incompatible with life in the postnatal period or allow survival into adulthood. Retinopathy is a recurrent feature in both the severely and mildly affected patients, which can be accompanied with other ophthalmological pathologies. Thanks to next-generation sequencing, patients originally identified with other inherited blinding diseases were reclassified as suffering from peroxisomal disorders. Read More

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http://dx.doi.org/10.1007/978-3-030-27378-1_52DOI Listing
February 2020

Pediatric liver diseases and ocular changes: What hepatologists and ophthalmologists should know and share with each other.

Dig Liver Dis 2020 01 13;52(1):1-8. Epub 2019 Dec 13.

Pediatric Clinic, Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", Baronissi, Italy. Electronic address:

Several rare pediatric liver disorders are accompanied by ophthalmic signs whose awareness and early identification may be of value in confirming/accelerating their diagnosis. Many of these signs are asymptomatic and can only be detected with an ophthalmological examination. Corneal signs are described in patients with Wilson's disease, Alagille's syndrome and some liver storage diseases. Read More

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http://dx.doi.org/10.1016/j.dld.2019.11.009DOI Listing
January 2020

Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Genet Med 2020 Apr 11;22(4):686-697. Epub 2019 Dec 11.

Department of Human Genetics and Pediatrics, McGill University, Montreal, QC, Canada.

Peroxisomal disorders are a clinically and genetically heterogeneous group of diseases caused by defects in peroxisomal biogenesis or function, usually impairing several metabolic pathways. Peroxisomal disorders are rare; however, the incidence may be underestimated due to the broad spectrum of clinical presentations. The inclusion of X-linked adrenoleukodystrophy to the Recommended Uniform Screening Panel for newborn screening programs in the United States may increase detection of this and other peroxisomal disorders. Read More

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http://dx.doi.org/10.1038/s41436-019-0713-9DOI Listing

Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia.

Hum Mol Genet 2020 Jan;29(2):286-294

Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham NC 27710, USA.

Glycogen storage disease type Ia (GSD Ia) is caused by autosomal mutations in glucose-6-phosphatase α catalytic subunit (G6PC) and can present with severe hypoglycemia, lactic acidosis and hypertriglyceridemia. In both children and adults with GSD Ia, there is over-accumulation of hepatic glycogen and triglycerides that can lead to steatohepatitis and a risk for hepatocellular adenoma or carcinoma. Here, we examined the effects of the commonly used peroxisomal proliferated activated receptor α agonist, fenofibrate, on liver and kidney autophagy and lipid metabolism in 5-day-old G6pc -/- mice serving as a model of neonatal GSD Ia. Read More

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http://dx.doi.org/10.1093/hmg/ddz290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003036PMC
January 2020

Label-Free Proteomics of the Fetal Pancreas Identifies Deficits in the Peroxisome in Rats with Intrauterine Growth Restriction.

Oxid Med Cell Longev 2019 3;2019:1520753. Epub 2019 Nov 3.

Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Aim: The objective of the present study was to identify differentially expressed proteins (DEPs) in the pancreas of a fetus with intrauterine growth restriction (IUGR) and to investigate the molecular mechanisms leading to adulthood diabetes in IUGR.

Methods: The IUGR rat model was induced by maternal protein malnutrition. The fetal pancreas was collected at embryonic day 20 (E20). Read More

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http://dx.doi.org/10.1155/2019/1520753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874927PMC

Spastic paraplegia as the predominant phenotype in a cohort of Chinese patients with adrenoleukodystrophy.

Mol Genet Genomic Med 2020 Jan 27;8(1):e1065. Epub 2019 Nov 27.

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.

Background: X-linked adrenoleukodystrophy (ALD) is one of the most common peroxisomal disorders characterized by abnormal accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues and caused by mutations within ABCD1. Clinically, ALD present with various phenotypes, ranging from asymptomatic type to rapidly progressive childhood cerebral form. However, no remarkable abnormality in cerebral white matter usually makes it difficult to distinguish adult ALD from hereditary spastic paraplegia (HSP). Read More

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http://dx.doi.org/10.1002/mgg3.1065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978395PMC
January 2020

The type-2 peroxisomal targeting signal.

Authors:
Markus Kunze

Biochim Biophys Acta Mol Cell Res 2020 02 18;1867(2):118609. Epub 2019 Nov 18.

Medical University of Vienna, Center for Brain Research, Department of Pathobiology of the Nervous System, Spitalgasse 4, 1090 Vienna, Austria. Electronic address:

The type-2 peroxisomal targeting signal (PTS2) is one of two peptide motifs destining soluble proteins for peroxisomes. This signal acts as amphiphilic α-helix exposing the side chains of all conserved residues to the same side. PTS2 motifs are recognized by a bipartite protein complex consisting of the receptor PEX7 and a co-receptor. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2019.118609DOI Listing
February 2020

Inborn errors of metabolism leading to neuronal migration defects.

J Inherit Metab Dis 2020 Jan 10;43(1):145-155. Epub 2019 Dec 10.

Department of Paediatrics and Adolescent Medicine, University Medical Centre Göttingen, Georg August University Göttingen, Göttingen, Germany.

The development and organisation of the human brain start in the embryonic stage and is a highly complex orchestrated process. It depends on series of cellular mechanisms that are precisely regulated by multiple proteins, signalling pathways and non-protein-coding genes. A crucial process during cerebral cortex development is the migration of nascent neuronal cells to their appropriate positions and their associated differentiation into layer-specific neurons. Read More

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http://dx.doi.org/10.1002/jimd.12194DOI Listing
January 2020

PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.

Proc Natl Acad Sci U S A 2019 12 18;116(49):24819-24829. Epub 2019 Nov 18.

Department of Medical Microbiology & Immunology, University of California Davis School of Medicine, Davis, CA 95616;

Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4 T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Read More

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http://dx.doi.org/10.1073/pnas.1908977116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900595PMC
December 2019

Longitudinal diffusion MRI as surrogate outcome measure for myelopathy in adrenoleukodystrophy.

Neurology 2019 12 12;93(23):e2133-e2143. Epub 2019 Nov 12.

From the Department of Paediatric Neurology, Emma Children's Hospital (I.C.H., W.J.C.v.B., J.M.B.W.V., M.E.), Laboratory Genetic Metabolic Diseases (S.K.), and Department of Biomedical Engineering & Physics (M.W.A.C.), Amsterdam UMC, University of Amsterdam, the Netherlands.

Objective: To prospectively determine the potential of diffusion MRI (dMRI) of the cervical spinal cord and the corticospinal tracts in brain as surrogate outcome measure for progression of myelopathy in men with adrenoleukodystrophy, as better outcome measures to quantify progression of myelopathy would enable clinical trials with fewer patients and shorter follow-up.

Methods: Clinical assessment of myelopathy included Expanded Disability Status Scale (EDSS), Severity Scoring System for Progressive Myelopathy (SSPROM), Timed Up-and-Go, and 6-Minute Walk Test. Applied dMRI metrics included fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Read More

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http://dx.doi.org/10.1212/WNL.0000000000008572DOI Listing
December 2019

Hematopoietic Stem Cell Transplantation in Inborn Errors of Metabolism.

Front Pediatr 2019 25;7:433. Epub 2019 Oct 25.

Metabolic and Blood and Marrow Transplant Units, Royal Manchester Children's Hospital, Manchester, United Kingdom.

Hematopoietic stem cell transplantation (HSCT) has been established as an effective therapy for selected inborn errors of metabolism. The success of HSCT in metabolic disease is best exemplified through the treatment of Hurler's syndrome, a lysosomal storage disease. Through the collaborative effort of several international centers, factors that predict successful patient and transplant outcomes have been identified. Read More

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http://dx.doi.org/10.3389/fped.2019.00433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824291PMC
October 2019

[Genetic analysis of a pedigree affected with X-linked adrenoleukodystrophy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Nov;36(11):1104-1106

Department of Neurology, the First People's Hospital of Wuyi County, Wuyi, Zhejiang 321200, China.

Objective: To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs.

Methods: Genomic DNA was extracted from peripheral blood samples of the patient and his mother. Potential variant was detected with a panel for genes associated with spastic paraplegia. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.11.012DOI Listing
November 2019

Leukoencephalopathy With Predominant Infratentorial Involvement Caused by a Novel ABCD1 Mutation: Does the Spinocerebellar Variant of Adrenoleukodystrophy Exist?

Neurologist 2019 Nov;24(6):194-197

Fondazione IRCCS Istituto Neurologico "C. Besta".

Introduction: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear.

Case Report: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. Read More

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http://dx.doi.org/10.1097/NRL.0000000000000252DOI Listing
November 2019

Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center.

J Pediatr (Rio J) 2019 Oct 31. Epub 2019 Oct 31.

Universidade Federal do Rio Grande do Sul (UFRGS), Programa de Pós Graduação em Ciências Médicas, Porto Alegre, RS, Brazil; Hospital de Clínicas de Porto Alegre (HCPA), Serviço de Genética Médica, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul (UFRGS), Departamento de Genética, Porto Alegre, RS, Brazil. Electronic address:

Objectives: To characterize cases of suspected congenital disorders of glycosylation (CDG) investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017.

Method: Observational, cross-sectional, retrospective study. The laboratory records of 1546 individuals (median age=36 months, 25-75 IQR=10-108; males=810) submitted to the TfIEF test during the period were reviewed. Read More

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http://dx.doi.org/10.1016/j.jped.2019.05.008DOI Listing
October 2019

Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy.

J Pediatr Endocrinol Metab 2019 Nov;32(11):1207-1215

Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different manifestations varying in patients and families. Methods Four pedigrees with X-ALD consisting of patients and healthy members were selected for investigation of ABCD1 gene mutations. Read More

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http://dx.doi.org/10.1515/jpem-2019-0244DOI Listing
November 2019

Mitochondrial dysfunction, AMPK activation and peroxisomal metabolism: A coherent scenario for non-canonical 3-methylglutaconic acidurias.

Biochimie 2020 Jan 15;168:53-82. Epub 2019 Oct 15.

Laboratory of Molecular Biology of the Gene, Department of Molecular Biology, ULB Immunology Research Center (UIRC), Free University of Brussels (ULB), Gosselies, Belgium.

The occurrence of 3-methylglutaconic aciduria (3-MGA) is a well understood phenomenon in leucine oxidation and ketogenesis disorders (primary 3-MGAs). In contrast, its genesis in non-canonical (secondary) 3-MGAs, a growing-up group of disorders encompassing more than a dozen of inherited metabolic diseases, is a mystery still remaining unresolved for three decades. To puzzle out this anthologic problem of metabolism, three clues were considered: (i) the variety of disorders suggests a common cellular target at the cross-road of metabolic and signaling pathways, (ii) the response to leucine loading test only discriminative for primary but not secondary 3-MGAs suggests these latter are disorders of extramitochondrial HMG-CoA metabolism as also attested by their failure to increase 3-hydroxyisovalerate, a mitochondrial metabolite accumulating only in primary 3-MGAs, (iii) the peroxisome is an extramitochondrial site possessing its own pool and displaying metabolism of HMG-CoA, suggesting its possible involvement in producing extramitochondrial 3-methylglutaconate (3-MG). Read More

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http://dx.doi.org/10.1016/j.biochi.2019.10.004DOI Listing
January 2020

Teaching NeuroImages: Frontal lobe involvement in adult-onset cerebral X-linked adrenoleukodystrophy.

Neurology 2019 09;93(13):e1326-e1327

From the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1212/WNL.0000000000008181DOI Listing
September 2019

Clinical, neuroimaging, biochemical, and genetic features in six Chinese patients with Adrenomyeloneuropathy.

BMC Neurol 2019 Sep 16;19(1):227. Epub 2019 Sep 16.

Department of Neurology, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, People's Republic of China.

Background: Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients.

Methods: We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Read More

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http://dx.doi.org/10.1186/s12883-019-1449-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745787PMC
September 2019
2 Reads
2.040 Impact Factor

Cervical Spine Deformities in Children With Rhizomelic Chondrodysplasia Punctata.

J Pediatr Orthop 2019 Oct;39(9):e680-e686

Department of Orthopedics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE.

Background: Cervical spine deformity in rhizomelic chondrodysplasia punctata (RCDP) has been described with different findings reported in the literature. However, available literature provides limited data from a few cases with magnetic resonance imaging (MRI) of the cervical spine. Our report describes the MRI findings in a group of children with RCDP, aiming to reach a better understanding of this pathology. Read More

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http://dx.doi.org/10.1097/BPO.0000000000001014DOI Listing
October 2019

Mevalonate kinase deficiency masked by cytomegalovirus infection and obscure liver disease.

Clin Chim Acta 2019 Nov 17;498:122-125. Epub 2019 Aug 17.

Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service (NHLS) Tshwane Academic Division, Pretoria, South Africa; Division of Chemical Pathology, University of Cape Town, South Africa. Electronic address:

Background: Chronic liver disease with conjugated hyperbilirubinaemia and failure to thrive can have multifactorial aetiologies. Investigations can be complex and difficult especially when obscured by a viral infection affecting liver function.

Methods: A 5 month old male infant was referred for investigation of chronic liver disease and a history of jaundice with multiple febrile episodes. Read More

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http://dx.doi.org/10.1016/j.cca.2019.08.014DOI Listing
November 2019
2 Reads

Teaching NeuroImages: X-linked adrenoleukodystrophy: Spinocerebellar variant.

Neurology 2019 08;93(7):e731-e732

From Lui Che Woo Institute of Innovative Medicine, Margaret K.L. Cheung Research Centre for Management of Parkinsonism, Chinese University of Hong Kong.

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http://dx.doi.org/10.1212/WNL.0000000000007958DOI Listing

ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells.

BMB Rep 2019 Sep;52(9):566-571

Department of Medical Oncology, Wuming Hospital of Guangxi Medical University, Naning 530199, China.

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid β-oxidation. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774419PMC
September 2019
2 Reads

Gene-Based Approaches to Inherited Neurometabolic Diseases.

Hum Gene Ther 2019 10 10;30(10):1222-1235. Epub 2019 Sep 10.

Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

In the last decade, the gene therapy (GT) field experienced a renaissance, thanks to crucial understandings and innovations in vector design, stem cell manipulation, conditioning protocols, and cell/vector delivery. These efforts were successfully coupled with unprecedented clinical results of the trials employing the newly developed technology and with the novel establishment of academic-industrial partnerships. A renewed and strengthened interest is rising in the development of gene-based approaches for inherited neurometabolic disorders with severe neurological involvement. Read More

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http://dx.doi.org/10.1089/hum.2019.190DOI Listing
October 2019
7 Reads

The fate of medium-chain fatty acids in very long-chain acyl‑CoA dehydrogenase deficiency (VLCADD): A matter of sex?

Biochim Biophys Acta Mol Cell Biol Lipids 2019 11 5;1864(11):1591-1605. Epub 2019 Aug 5.

Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Mathildenstrasse 1, Freiburg, Germany. Electronic address:

Medium-chain-triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders (lcFAOD). Long-term treatment with MCT led to a sexually dimorphic response in the mouse model of very-long-chain-acyl-CoA-dehydrogenase-deficiency (VLCAD) with the subsequent development of a metabolic syndrome in female mice. In order to evaluate the molecular mechanisms responsible for this sex specific response we performed a comprehensive metabolic phenotyping, SILAC-based quantitative proteomics and characterized the involved signaling pathways by western blot analysis and gene expression. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.08.001DOI Listing
November 2019
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Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex.

Int J Mol Sci 2019 Aug 1;20(15). Epub 2019 Aug 1.

Institute of Biochemistry and Biology, University of Potsdam, D-14476 Potsdam, Germany.

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. Read More

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http://dx.doi.org/10.3390/ijms20153756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696164PMC

X-linked adrenoleukodystrophy diagnosed in three brothers.

Pediatr Endocrinol Diabetes Metab 2019 ;25(2):95-98

Department of Basic Medical Sciences, Wroclaw Medical University.

Adrenoleukodystrophy is a genetic diseases classified in the group of peroxisomal disorders caused by mutations in ABCD1, gene located on the X chromosome (Xq28). It demonstrates X-linked recessive inheritance. There is an accumulation of very long-chain fatty acids (VLCFA) in plasma and all tissues in the process of ALD. Read More

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http://dx.doi.org/10.5114/pedm.2019.85821DOI Listing
February 2020
4 Reads

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder.

JCI Insight 2019 07 25;4(14). Epub 2019 Jul 25.

Department of Nutrition and.

Mitochondrial dysfunction characterizes many rare and common age-associated diseases. The biochemical consequences, underlying clinical manifestations, and potential therapeutic targets, remain to be better understood. We tested the hypothesis that lipid dyshomeostasis in mitochondrial disorders goes beyond mitochondrial fatty acid β-oxidation, particularly in liver. Read More

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http://dx.doi.org/10.1172/jci.insight.123231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675547PMC
July 2019
2 Reads

Pearls & Oy-sters: Adolescent-onset adrenomyeloneuropathy and arrested cerebral adrenoleukodystrophy.

Neurology 2019 07;93(2):81-84

From the Department of Medicine (J.E.L.), University of Illinois at Chicago; Division of Child Neurology, Department of Neurology (J.E.L., E.A.A., A.H., J.M.B.), Division of Medical Genetics, Department of Pediatrics (C.U., A.D.I.), and Department of Anesthesia (J.C.), Columbia University College of Physicians and Surgeons; The Columbia University Irving Medical Center (J.E.L, E.A.A, A.H, J.M.B, C.U., A.D.I, J.J.C); and Division of Child Neurology (E.J.M.), Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York.

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http://www.neurology.org/lookup/doi/10.1212/WNL.000000000000
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http://dx.doi.org/10.1212/WNL.0000000000007755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656648PMC
July 2019
3 Reads