4,497 results match your criteria Peroxisomal Disorders


Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania.

Int J Neonatal Screen 2022 Mar 23;8(2). Epub 2022 Mar 23.

Section of Biochemical Genetics, Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in , which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Read More

View Article and Full-Text PDF

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy.

Front Nutr 2022 8;9:864358. Epub 2022 Apr 8.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). Read More

View Article and Full-Text PDF

[Analysis of MVK gene variant in a child with high IgD syndrome caused by mevalonate kinase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Apr;39(4):413-416

Deparment of Paediatrics, The Third People' s Hospital of Hubei Province, Wuhan, Hubei 430415, China.

Objective: To analyze the clinical and genetic features of a patient with mevalonate kinase deficiency (MKD).

Methods: Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing. Read More

View Article and Full-Text PDF

Late onset AMACR deficiency with metabolic stroke-like episodes and seizures.

BMJ Case Rep 2022 Apr 15;15(4). Epub 2022 Apr 15.

Department of Neurology, Leeds General Infirmary, Leeds, UK.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. Read More

View Article and Full-Text PDF

Homozygous V377I mutation causing mevalonate kinase.

BMJ Case Rep 2022 Apr 6;15(4). Epub 2022 Apr 6.

Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, EPE, Setubal, Portugal.

Hyperimmunoglobulinaemia D syndrome (HIDS) is a rare autosomal recessive disorder caused by mutations in the mevalonate kinase (MVK) gene, located on chromosome 12. The most common mutation identified in MVK gene so far is V377I. Compound heterozygotes that include this variant may exhibit a more severe phenotype of the disease and homozygotes are rarely found in clinical practice probably they express a milder phenotype. Read More

View Article and Full-Text PDF

Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism.

Kidney360 2021 Oct 16;2(10):1576-1591. Epub 2021 Jul 16.

Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Background: Multiple studies of tissue and cell samples from patients and preclinical models of autosomal dominant polycystic kidney disease report abnormal mitochondrial function and morphology and suggest metabolic reprogramming is an intrinsic feature of this disease. Peroxisomes interact with mitochondria physically and functionally, and congenital peroxisome biogenesis disorders can cause various phenotypes, including mitochondrial defects, metabolic abnormalities, and renal cysts. We hypothesized that a peroxisomal defect might contribute to the metabolic and mitochondrial impairments observed in autosomal dominant polycystic kidney disease. Read More

View Article and Full-Text PDF
October 2021

Current treatment options for monogenic periodic fever syndromes - the role of interleukin 1 inhibitors.

Cas Lek Cesk 2022 ;161(1):3-10

Monogenic periodic fever syndromes are heterogeneous group of autoinflammatory diseases including distinct syndromes, such as cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor alpha receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). Individual diseases differ in pathogenesis, clinical manifestations, and severity. However, cytokines from the interleukin 1 (IL-1) family play a key role in all of them. Read More

View Article and Full-Text PDF

Insights Into the Peroxisomal Protein Inventory of Zebrafish.

Front Physiol 2022 28;13:822509. Epub 2022 Feb 28.

College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, United Kingdom.

Peroxisomes are ubiquitous, oxidative subcellular organelles with important functions in cellular lipid metabolism and redox homeostasis. Loss of peroxisomal functions causes severe disorders with developmental and neurological abnormalities. Zebrafish are emerging as an attractive vertebrate model to study peroxisomal disorders as well as cellular lipid metabolism. Read More

View Article and Full-Text PDF
February 2022

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy.

Cells 2022 03 7;11(5). Epub 2022 Mar 7.

Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.

Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in , the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Read More

View Article and Full-Text PDF

Early Neuroimaging in Zellweger Spectrum Disorders.

Neurol India 2022 Jan-Feb;70(1):172-173

Department of Pediatric Neurology, PD Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India.

View Article and Full-Text PDF

Restless Legs Syndrome in X-linked adrenoleukodystrophy.

Sleep Med 2022 03 16;91:31-34. Epub 2022 Feb 16.

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Objective/background: X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease that causes progressive gait and balance problems. Leg discomfort, sleep disturbances, and pain contribute to daily disability. We sought to investigate the prevalence and severity of Restless Legs Syndrome (RLS) in patients with ALD. Read More

View Article and Full-Text PDF

Time to Transplant in X-Linked Adrenoleukodystrophy.

J Child Neurol 2022 04 3;37(5):397-400. Epub 2022 Mar 3.

7061Intermountain Healthcare, Salt Lake City, Utah, USA.

Objectives: Cerebral X-linked adrenoleukodystrophy (cALD) is an inflammatory demyelination of the brain that can lead to death unless treated by hematopoietic stem cell transplantation. Survival and improved outcomes for cerebral adrenoleukodystrophy are associated with hematopoietic stem cell transplantation at earliest evidence of disease on magnetic resonance imaging (MRI). Our goal was to determine average duration between diagnosis of cALD and hematopoietic stem cell transplantation. Read More

View Article and Full-Text PDF

Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses.

Cell Rep 2022 03;38(9):110433

Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada; Dalhousie University, Department of Pediatrics, Halifax, NS B3K 6R8, Canada. Electronic address:

Phagocytosis, signal transduction, and inflammatory responses require changes in lipid metabolism. Peroxisomes have key roles in fatty acid homeostasis and in regulating immune function. We find that Drosophila macrophages lacking peroxisomes have perturbed lipid profiles, which reduce host survival after infection. Read More

View Article and Full-Text PDF

Renal tubular peroxisomes are dispensable for normal kidney function.

JCI Insight 2022 02 22;7(4). Epub 2022 Feb 22.

Department of Biomedical Sciences.

Peroxisomes are specialized cellular organelles involved in a variety of metabolic processes. In humans, mutations leading to complete loss of peroxisomes cause multiorgan failure (Zellweger's spectrum disorders, ZSD), including renal impairment. However, the (patho)physiological role of peroxisomes in the kidney remains unknown. Read More

View Article and Full-Text PDF
February 2022

Uveitis, glaucoma, and cataract with mevalonate kinase deficiency.

J AAPOS 2022 04 11;26(2):93-95. Epub 2022 Feb 11.

Department of Pediatric Ophthalmology, Jyotirmay Eye Clinic for Children and Adult Squint and Ocular Motility Laboratory, Thane, Maharashtra, India.

We report 7 years of follow-up data on ocular findings in a 2-month-old boy who presented with early-onset bilateral granulomatous panuveitis with subsequent development of secondary glaucoma and total cataract, along with multisystem involvement. He was diagnosed with mevalonate kinase deficiency (MKD), with a homozygous missense variant in exon-6 of the mevalonate kinase (MVK) gene on chromosome-12 that resulted in the substitution of aspartic acid for asparagine at codon 205 (p.Asn205Asp). Read More

View Article and Full-Text PDF

Therapeutic regulation of autophagy in hepatic metabolism.

Acta Pharm Sin B 2022 Jan 28;12(1):33-49. Epub 2021 Jul 28.

Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ that governs body energy metabolism. Read More

View Article and Full-Text PDF
January 2022

Peroxisome-generated succinate induces lipid accumulation and oxidative stress in the kidneys of diabetic mice.

J Biol Chem 2022 03 4;298(3):101660. Epub 2022 Feb 4.

School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan, China. Electronic address:

Diabetes normally causes lipid accumulation and oxidative stress in the kidneys, which plays a critical role in the onset of diabetic nephropathy; however, the mechanism by which dysregulated fatty acid metabolism increases lipid and reactive oxygen species (ROS) formation in the diabetic kidney is not clear. As succinate is remarkably increased in the diabetic kidney, and accumulation of succinate suppresses mitochondrial fatty acid oxidation and increases ROS formation, we hypothesized that succinate might play a role in inducing lipid and ROS accumulation in the diabetic kidney. Here we demonstrate a novel mechanism by which diabetes induces lipid and ROS accumulation in the kidney of diabetic animals. Read More

View Article and Full-Text PDF

Clinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series.

Neurogenetics 2022 04 2;23(2):115-127. Epub 2022 Feb 2.

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

Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal recessive disorders caused by mutations in any of 13 PEX genes involved in peroxisome assembly. Compared to other PEX-related disorders, some PEX16 defects are associated with an atypical phenotype consisting of spasticity, cerebellar dysfunction, preserved cognition, and prolonged survival. In this case series, medical records and brain MRIs from 7 patients with this PEX16 presentation were reviewed to further characterize this phenotype. Read More

View Article and Full-Text PDF

Sequential lipidomic, metabolomic, and proteomic analyses of serum, liver, and heart tissue specimens from peroxisomal biogenesis factor 11α knockout mice.

Anal Bioanal Chem 2022 Mar 27;414(6):2235-2250. Epub 2022 Jan 27.

Institute of Inorganic and Analytical Chemistry, Justus Liebig University Giessen, 35392, Giessen, Germany.

Peroxisomes are versatile single membrane-enclosed cytoplasmic organelles, involved in reactive oxygen species (ROS) and lipid metabolism and diverse other metabolic processes. Peroxisomal disorders result from mutations in Pex genes-encoded proteins named peroxins (PEX proteins) and single peroxisomal enzyme deficiencies. The PEX11 protein family (α, β, and γ isoforms) plays an important role in peroxisomal proliferation and fission. Read More

View Article and Full-Text PDF

A Novel Variant in the AGPS Gene Causes the Rare Rhizomelic Chondrodysplasia Punctata Type 3: A Case Report.

Cureus 2021 Dec 20;13(12):e20543. Epub 2021 Dec 20.

Pathology and Laboratory Medicine/Genetics, King Abdulaziz Medical City Jeddah, Jeddah, SAU.

Rhizomelic chondrodysplasia punctata (RCDP) is a devastating medical condition for patients and their families. It is a rare peroxisomal autosomal recessive disorder. It was recognized clinically with skeletal abnormalities and intellectual disabilities mainly due to plasmalogen deficiency. Read More

View Article and Full-Text PDF
December 2021

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation.

Int J Mol Sci 2022 Jan 17;23(2). Epub 2022 Jan 17.

Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.

Peroxisomal fatty acid α-oxidation is an essential pathway for the degradation of β-carbon methylated fatty acids such as phytanic acid. One enzyme in this pathway is 2-hydroxyacyl CoA lyase (HACL1), which is responsible for the cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA. Hacl1 deficient mice do not present with a severe phenotype, unlike mice deficient in other α-oxidation enzymes such as phytanoyl-CoA hydroxylase deficiency (Refsum disease) in which neuropathy and ataxia are present. Read More

View Article and Full-Text PDF
January 2022

Structure and Function of the Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy.

Cells 2022 01 14;11(2). Epub 2022 Jan 14.

Department of Pediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam Neuroscience, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

The progressive neurometabolic disorder X-linked adrenoleukodystrophy (ALD) is caused by pathogenic variants in the gene, which encodes the peroxisomal ATP-binding transporter for very-long-chain fatty acids. The clinical spectrum of ALD includes adrenal insufficiency, myelopathy, and/or leukodystrophy. A complicating factor in disease management is the absence of a genotype-phenotype correlation in ALD. Read More

View Article and Full-Text PDF
January 2022

Cell Type-Selective Loss of Peroxisomal β-Oxidation Impairs Bipolar Cell but Not Photoreceptor Survival in the Retina.

Cells 2022 01 4;11(1). Epub 2022 Jan 4.

Laboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.

Retinal degeneration is a common feature in peroxisomal disorders leading to blindness. Peroxisomes are present in the different cell types of the retina; however, their precise contribution to retinal integrity is still unclear. We previously showed that mice lacking the central peroxisomal β-oxidation enzyme, multifunctional protein 2 (MFP2), develop an early onset retinal decay including photoreceptor cell death. Read More

View Article and Full-Text PDF
January 2022

An Infant with Blended Phenotype of Zellweger Spectrum Disorder and Congenital Muscular Dystrophy.

Ann Indian Acad Neurol 2021 Sep-Oct;24(5):759-760. Epub 2021 Feb 24.

Department of Medical Genetics, Fernandez Foundation, Hyderabad, Telangana, India.

We report a newborn born to a consanguineous couple with antenatally detected dilatation of third ventricle, unilateral talipes, and intra uterine growth retardation. On examination, there was facial dysmorphism, hypotonia, encephalopathy, joint laxity and muscle hypertrophy in addition to left foot talipes. On evaluation, there were renal cortical cysts, rhizomelia, chondrodysplasia punctata and elevated muscle enzymes, along with a dilated third ventricle. Read More

View Article and Full-Text PDF
February 2021

Typical and atypical phenotype and neuroimaging of X-linked adrenoleukodystrophy in a Chinese cohort.

Neurol Sci 2022 May 8;43(5):3255-3263. Epub 2022 Jan 8.

Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, 100730, China.

Objective: The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD.

Methods: Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. Read More

View Article and Full-Text PDF

The Peroxisome-Autophagy Redox Connection: A Double-Edged Sword?

Front Cell Dev Biol 2021 16;9:814047. Epub 2021 Dec 16.

Laboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

Peroxisomes harbor numerous enzymes that can produce or degrade hydrogen peroxide (HO). Depending on its local concentration and environment, this oxidant can function as a redox signaling molecule or cause stochastic oxidative damage. Currently, it is well-accepted that dysfunctional peroxisomes are selectively removed by the autophagy-lysosome pathway. Read More

View Article and Full-Text PDF
December 2021

[Clinical features and genetic analysis of a Chinese pedigree affected with X-linked adrenoleukodystrophy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jan;39(1):60-63

Department of Neurology, Huizhou First People's Hospital, Huizhou, Guangdong 516003, China.

Objective: To analyze the clinical features and variants of ABCD1 gene in a Chinese pedigree affected with X-linked adrenoleukodystrophy.

Methods: Clinical data of the proband were collected and analyzed. Potential variant of the ABCD1 gene were analyzed by PCR and Sanger sequencing of the proband, his parents and 100 unrelated healthy individuals. Read More

View Article and Full-Text PDF
January 2022

A clinically validated method to separate and quantify underivatized acylcarnitines and carnitine metabolic intermediates using mixed-mode chromatography with tandem mass spectrometry.

J Chromatogr A 2022 Jan 16;1663:462749. Epub 2021 Dec 16.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 W. Walnut St., IB-344C, Indianapolis, IN 46202, United States. Electronic address:

Acylcarnitines are intermediate metabolites of the mitochondria that serve as biomarkers for inherited disorders of fatty acid oxidation and amino acid metabolism. The prevailing clinical method used to quantify acylcarnitines involves flow-injection tandem mass spectrometry, an approach with a number of limitations; foremost the inability to separate and therefore distinguish key isobaric acylcarnitine species. To address these issues, we report a clinically validated liquid chromatography tandem mass spectrometry method to quantify acylcarnitines, free carnitine, and carnitine metabolic intermediates in human plasma. Read More

View Article and Full-Text PDF
January 2022

Case Report: Mevalonic Aciduria Complicated by Acute Myeloid Leukemia After Hematopoietic Stem Cell Transplantation.

Front Immunol 2021 7;12:782780. Epub 2021 Dec 7.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, South Korea.

Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Read More

View Article and Full-Text PDF
February 2022