29,467 results match your criteria Lysosomal Storage Disease


Cardiac manifestations in patients with classical or cardiac subtype of Fabry disease.

J Chin Med Assoc 2020 Jun 22. Epub 2020 Jun 22.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder engendered by a deficiency of the enzyme α-galactosidase A, leading to a systemic accumulation of glycolipids. Studies have reported that the cardiac subtype of FD has a later onset and minimal extracardiac involvement. However, whether the severity of cardiac involvement differs between the classic and cardiac subtypes of FD remains unclear. Read More

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http://dx.doi.org/10.1097/JCMA.0000000000000379DOI Listing

Peripheral Nerve Compression Syndromes in Children.

J Hand Surg Am 2020 Jul 6. Epub 2020 Jul 6.

Department of Pediatric Orthopaedics and Adult Foot and Ankle Surgery, Orthopedic Hospital Speising, Vienna, Austria. Electronic address:

Nontraumatic neuropathies of the upper limb are rare in children. In this paper, we present the latest updates in this field and also critically review the diagnosis and treatment of nerve compression syndromes in children. This review describes the most common manifestations including idiopathic carpal tunnel syndrome (CTS), CTS occurring as a component of lysosomal storage diseases (mucopolysaccharidosis) and hereditary neuropathies, ulnar nerve neuropathy, and atraumatic radial nerve neuropathies. Read More

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http://dx.doi.org/10.1016/j.jhsa.2020.04.028DOI Listing

Distinct Modes of Balancing Glomerular Cell Proteostasis in Mucolipidosis Type II and III Prevent Proteinuria.

J Am Soc Nephrol 2020 Jul 8. Epub 2020 Jul 8.

Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Background: The mechanisms balancing proteostasis in glomerular cells are unknown. Mucolipidosis (ML) II and III are rare lysosomal storage disorders associated with mutations of the Golgi-resident GlcNAc-1-phosphotransferase, which generates mannose 6-phosphate residues on lysosomal enzymes. Without this modification, lysosomal enzymes are missorted to the extracellular space, which results in lysosomal dysfunction of many cell types. Read More

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http://dx.doi.org/10.1681/ASN.2019090960DOI Listing

Cornea Verticillata in classical Fabry disease, first from Sri Lanka: a case report.

BMC Pediatr 2020 Jul 8;20(1):338. Epub 2020 Jul 8.

Department of Paediatrics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.

Background: Fabry disease is a rare inborn error of metabolism with profound clinical consequences if untreated. It is caused by the deficiency of α galactosidase A enzyme and is the only lysosomal storage disorder with an X linked inheritance. Confirmation requires genetic analysis of Galactosidase Alpha (GLA) Gene, which is often a challenge in resource-poor settings. Read More

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http://dx.doi.org/10.1186/s12887-020-02237-zDOI Listing

Genetic Management Algorithm in High-Risk Fabry Disease Cases; especially in Female Indexes with Mutations.

Endocr Metab Immune Disord Drug Targets 2020 Jul 8. Epub 2020 Jul 8.

Department of Medical Genetics, Intergen Genetic Centre, Ankara. Turkey.

Background: Fabry Disease (FD, OMIM#301500) is a progressive, life-threatening, multisystemic, rare lysosomal storage disease. Today, approximately 1000 mutations are recorded in the Human Gene Mutation Database (www.hgmd. Read More

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http://dx.doi.org/10.2174/1871530320666200708135826DOI Listing

An Expert Consensus Document on the Management of Cardiovascular Manifestations of Fabry Disease.

Eur J Heart Fail 2020 Jul 8. Epub 2020 Jul 8.

Institute of Cardiovascular Science, University College London and Barts Heart Centre, London, UK.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A gene (GLA) that leads to reduced or undetectable α-galactosidase A (AGAL-A) enzyme activity and progressive accumulation of globotriaosylceramide (Gb ) and its deacylated form globotriaosylsphingosine (lysoGb ) in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. Read More

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http://dx.doi.org/10.1002/ejhf.1960DOI Listing

Intravitreal enzyme replacement inhibits progression of retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis.

Exp Eye Res 2020 Jul 4:108135. Epub 2020 Jul 4.

Neurodegenerative Diseases Research Laboratory, University of Missouri, Columbia, MO, 65212, USA. Electronic address:

CLN2 neuronal ceroid lipofuscinosis is a rare recessive hereditary retinal and neurodegenerative disease resulting from deleterious sequence variants in TPP1 that encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Children with this disorder develop normally, but starting at 2-4 years of age begin to exhibit neurological signs and visual deficits. Vision loss that progresses to blindness is associated with progressive retinal degeneration and impairment of retinal function. Read More

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http://dx.doi.org/10.1016/j.exer.2020.108135DOI Listing

Metachromatic leukodystrophy genotypes in The Netherlands reveal novel pathogenic ARSA variants in non-Caucasian patients.

Neurogenetics 2020 Jul 7. Epub 2020 Jul 7.

Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children's Hospital, Amsterdam University Medical Center, VU University Amsterdam and Amsterdam Neuroscience, De Boelelaan, 1117, Amsterdam, The Netherlands.

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited sulfatide storage disease caused by deficient activity of the lysosomal enzyme arylsulfatase A (ASA). Genetic analysis of the ARSA gene is important in MLD diagnosis and screening of family members. In addition, more information on genotype prevalence will help interpreting MLD population differences between countries. Read More

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http://dx.doi.org/10.1007/s10048-020-00621-6DOI Listing

Nephropathic Cystinosis: A Distinct Form of CKD-Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23.

J Am Soc Nephrol 2020 Jul 6. Epub 2020 Jul 6.

Skeletal Disorders and Mineral Homeostasis Section, National Institutes of Dental and Craniofacial Research, Bethesda, Maryland.

Background: The rare lysosomal storage disease nephropathic cystinosis presents with renal Fanconi syndrome that evolves in time to CKD. Although biochemical abnormalities in common causes of CKD-mineral and bone disorder have been defined, it is unknown if persistent phosphate wasting in nephropathic cystinosis is associated with a biochemical mineral pattern distinct from that typically observed in CKD-mineral and bone disorder.

Methods: We assessed and compared determinants of mineral homeostasis in patients with nephropathic cystinosis across the predialysis CKD spectrum to these determinants in age- and CKD stage-matched patients, with causes of CKD other than nephropathic cystinosis. Read More

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http://dx.doi.org/10.1681/ASN.2019111172DOI Listing

Efficient engraftment of genetically modified cells is necessary to ameliorate central nervous system involvement of murine model of mucopolysaccharidosis type II by hematopoietic stem cell targeted gene therapy.

Mol Genet Metab 2020 Jun 24. Epub 2020 Jun 24.

Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. Electronic address:

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease (LSD) caused by a deficiency of the iduronate-2-sulfatase (IDS) that catabolizes glycosaminoglycans (GAGs). Abnormal accumulations of GAGs in somatic cells lead to various manifestations including central nervous system (CNS) disease. Enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are the currently available therapy for MPS II, but both therapies fail to improve CNS manifestations. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.06.007DOI Listing

A systematic review and meta-analysis of published cases reveals the natural disease history in Multiple Sulfatase Deficiency.

J Inherit Metab Dis 2020 Jul 4. Epub 2020 Jul 4.

Department of Medical Statistics, University Medical Center Göttingen, Germany.

Multiple Sulfatase Deficiency (MSD, MIM#272200) is an ultra-rare lysosomal storage disorder arising from mutations in the SUMF1 gene, which encodes the formylglycine-generating enzyme (FGE). FGE is necessary for the activation of sulfatases, a family of enzymes that are involved in the degradation of sulfated substrates such as glycosaminoglycans and sulfolipids. SUMF1 mutations lead to functionally impaired FGE and individuals with MSD demonstrate clinical signs of single sulfatase deficiencies, including metachromatic leukodystrophy (MLD) and several mucopolysaccharidosis (MPS) subtypes. Read More

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http://dx.doi.org/10.1002/jimd.12282DOI Listing

Engineering monocyte/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing.

Nat Commun 2020 Jul 3;11(1):3327. Epub 2020 Jul 3.

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebroside activity. Its hallmark manifestations are attributed to infiltration and inflammation by macrophages. Current therapies for Gaucher disease include life-long intravenous administration of recombinant glucocerebroside and orally-available glucosylceramide synthase inhibitors. Read More

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http://dx.doi.org/10.1038/s41467-020-17148-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335164PMC

Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment.

Mol Genet Metab 2020 Jun 24. Epub 2020 Jun 24.

Clinical Development, Sanofi Genzyme, Cambridge, MA, United States of America.

The liver is a major site of lipoprotein synthesis and metabolism. Liver manifestations of chronic visceral ASMD include hepatomegaly, fibrosis, elevated liver enzymes and a pro-atherogenic lipid profile. Measurements of sphingomyelin (SM) levels in liver biopsies and lyso-SM in plasma were used as pharmacodynamic biomarkers. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.06.010DOI Listing

Clinical relevance of endpoints in clinical trials for acid sphingomyelinase deficiency enzyme replacement therapy.

Mol Genet Metab 2020 Jun 24. Epub 2020 Jun 24.

Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A).

Purpose And Methods: We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DL) and splenomegaly, with clinical parameters and outcome measures. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.06.008DOI Listing

Bridging the Gap Between Vessels and Nerves in Fabry Disease.

Front Neurosci 2020 16;14:448. Epub 2020 Jun 16.

Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Purpose: Fabry disease frequently includes pain as an early disease feature, which was characterized as a dysfunctional processing of somatosensory information in various studies. The pathomechanism involves the mutation in the x-chromosomal GLA-gene and a consequent reduction of the α-galactosidase. This results in an insufficient reduction of globotriaosylceramide (GL3). Read More

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http://dx.doi.org/10.3389/fnins.2020.00448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308469PMC

miR-143 Regulates Lysosomal Enzyme Transport across the Blood-Brain Barrier and Transforms CNS Treatment for Mucopolysaccharidosis Type I.

Mol Ther 2020 Jun 15. Epub 2020 Jun 15.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45219, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA. Electronic address:

During brain maturation, cation-independent mannose-6-phosphate receptor (CI-MPR), a key transporter for lysosomal hydrolases, decreases significantly on the blood-brain barrier (BBB). Such a phenomenon leads to poor brain penetration of therapeutic enzymes and subsequent failure in reversing neurological complications in patients with neuropathic lysosomal storage diseases (nLSDs), such as Hurler syndrome (severe form of mucopolysaccharidosis type I [MPS I]). In this study, we discover that upregulation of microRNA-143 (miR-143) contributes to the decline of CI-MPR on the BBB during development. Read More

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http://dx.doi.org/10.1016/j.ymthe.2020.06.011DOI Listing

Enhancing the Activity of Glucocerebrosidase as a Treatment for Parkinson Disease.

CNS Drugs 2020 Jul 1. Epub 2020 Jul 1.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.

Mutations in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson disease (PD). Homozygous or compound heterozygous GBA1 mutations cause the lysosomal storage disorder Gaucher disease (GD), characterized by deficient activity of the glucocerebrosidase enzyme (GCase). Both individuals with GD type I and heterozygous carriers of pathogenic variants of GBA1 have an increased risk of developing PD, by approximately ten- to 20-fold compared to non-carriers. Read More

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http://dx.doi.org/10.1007/s40263-020-00746-0DOI Listing

Diagnosis and Screening of Patients with Fabry Disease.

Ther Clin Risk Manag 2020 22;16:551-558. Epub 2020 Jun 22.

Department of Medicine I, Klinikum Vest, Knappschaftskrankenhaus Recklinghausen, Academic Teaching Hospital, Ruhr-University Bochum, Recklinghausen, Germany.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by absence or deficient activity of α-galactosidase A (α-Gal A) due to mutations in the α-galactosidase A gene (), leading to progressive accumulation of globotriaosylceramide (Gb3) in tissues and organs including heart, kidney, the eyes, vascular endothelium, the nervous system and the skin. Cardiac involvement is leading to fatal complications and reduced life expectancy. FD is treatable with disease-specific treatment (enzyme replacement therapy (ERT) or with chaperone therapy). Read More

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http://dx.doi.org/10.2147/TCRM.S247814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319521PMC

Treatment Efficiency in Gaucher Patients Can Reliably Be Monitored by Quantification of Lyso-Gb1 Concentrations in Dried Blood Spots.

Int J Mol Sci 2020 Jun 27;21(13). Epub 2020 Jun 27.

CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany.

Gaucher disease (GD) is a lysosomal storage disorder that responds well to enzyme replacement therapy (ERT). Certain laboratory parameters, including blood concentration of glucosylsphingosine (Lyso-Gb1), the lyso-derivate of the common glycolipid glucocerebroside, correlate with clinical improvement and are therefore considered candidate-monitoring biomarkers. Whether they can indicate a reduction or loss of treatment efficiency, however, has not been systematically addressed for obvious reasons. Read More

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http://dx.doi.org/10.3390/ijms21134577DOI Listing

Neuropathophysiology, Genetic Profile, and Clinical Manifestation of Mucolipidosis IV-A Review and Case Series.

Int J Mol Sci 2020 Jun 26;21(12). Epub 2020 Jun 26.

Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK.

Mucolipidosis type IV (MLIV) is an ultra-rare lysosomal storage disorder caused by biallelic mutations in gene encoding the transient receptor potential channel mucolipin-1. So far, 35 pathogenic or likely pathogenic MLIV-related variants have been described. Clinical manifestations include severe intellectual disability, speech deficit, progressive visual impairment leading to blindness, and myopathy. Read More

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http://dx.doi.org/10.3390/ijms21124564DOI Listing

A tailored Cln3 mouse model for testing therapeutic interventions in CLN3 Batten disease.

Sci Rep 2020 Jun 29;10(1):10591. Epub 2020 Jun 29.

Pediatrics and Rare Diseases Group, Sanford Research, 2301 E. 60th N, Sioux Falls, SD, 57104, USA.

CLN3 Batten disease (CLN3 disease) is a pediatric lysosomal storage disorder that presents with progressive blindness, motor and cognitive decline, seizures, and premature death. CLN3 disease results from mutations in CLN3 with the most prevalent mutation, a 966 bp deletion spanning exons 7-8, affecting ~ 75% of patients. Mouse models with complete Cln3 deletion or Cln3 mutation have been invaluable for learning about both the basic biology of CLN3 and the underlying pathological changes associated with CLN3 disease. Read More

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http://dx.doi.org/10.1038/s41598-020-67478-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324379PMC

Identification of Brain-Specific Treatment Effects in NPC1 Disease by Focusing on Cellular and Molecular Changes of Sphingosine-1-Phosphate Metabolism.

Int J Mol Sci 2020 Jun 24;21(12). Epub 2020 Jun 24.

Research Group Anatomy, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany.

Niemann-Pick type C1 (NPC1) is a lysosomal storage disorder, inherited as an autosomal-recessive trait. Mutations in the gene result in malfunction of the NPC1 protein, leading to an accumulation of unesterified cholesterol and glycosphingolipids. Beside visceral symptoms like hepatosplenomegaly, severe neurological symptoms such as ataxia occur. Read More

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http://dx.doi.org/10.3390/ijms21124502DOI Listing

Transplantation of Stem Cells as a Potential Therapeutic Strategy in Neurodegenerative Disorders.

Curr Stem Cell Res Ther 2020 Jun 28. Epub 2020 Jun 28.

Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz. Iran.

Stem cells are considered to have significant capacity to differentiate into various cell types in humans or animals. Unlike specialized cells, these cells can proliferate several times to produce millions of cells. Nowadays, pluripotent stem cells are important candidates to provide a renewable source for replacement of cells in tissues of interest. Read More

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http://dx.doi.org/10.2174/1574888X15666200628141314DOI Listing

Enzyme therapy: a forerunner in catalyzing a healthy society?

Expert Opin Biol Ther 2020 Jul 8:1-23. Epub 2020 Jul 8.

Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University , Doha, Qatar.

Introduction: The use of enzymes in various industries has been prevalent for centuries. However, their potency as therapeutics remained latent until the late 1950 s, when scientists finally realized the gold mine they were sitting on. Enzyme therapy has seen rapid development over the past few decades and has been widely used for the therapy of myriad diseases, including lysosomal storage disorders, cancer, Alzheimer's disease, irritable bowel syndrome, exocrine pancreatic insufficiency, and hyperuricemia. Read More

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http://dx.doi.org/10.1080/14712598.2020.1787980DOI Listing

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value.

Front Neurosci 2020 11;14:579. Epub 2020 Jun 11.

Neuropharmacology, QPS Austria GmbH, Grambach, Austria.

Neurofilament-light chain (NF-L) is a well-known clinical biomarker of many neurodegenerative diseases. By analyzing amyotrophic lateral sclerosis (ALS) patients cerebrospinal fluid (CSF) or plasma, progression of NF-L levels can forecast conversion from the presymptomatic to symptomatic stage and time of survival. The use of plasma for NF-L measurement makes this biomarker exceptionally valuable for clinical studies since sample collection can be performed repeatedly without causing much harm. Read More

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http://dx.doi.org/10.3389/fnins.2020.00579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300175PMC

Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retina pigment epithelium.

Biochim Biophys Acta Mol Basis Dis 2020 Jun 24:165883. Epub 2020 Jun 24.

Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, United States; Markey Cancer Center, University of Kentucky, Lexington, KY, United States. Electronic address:

Juvenile neuronal ceroid lipofuscinosis (JNCL, aka. juvenile Batten disease or CLN3 disease) is a lysosomal storage disease characterized by progressive blindness, seizures, cognitive and motor failures, and premature death. JNCL is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene, whose function is unclear. Read More

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http://dx.doi.org/10.1016/j.bbadis.2020.165883DOI Listing

Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice.

Mol Ther 2020 Jun 19. Epub 2020 Jun 19.

Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address:

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme β-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. Read More

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http://dx.doi.org/10.1016/j.ymthe.2020.06.021DOI Listing

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease.

BMC Med Genet 2020 Jun 26;21(1):137. Epub 2020 Jun 26.

AP-HM, Centre de Néphrologie et Transplantation Rénale, CHU de la Conception, AP-HM, Marseille, France.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes.

Case Presentation: The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Read More

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http://dx.doi.org/10.1186/s12881-020-01071-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320597PMC

Genotype/phenotype relationship in Gaucher disease patients. Novel mutation in glucocerebrosidase gene.

Clin Chem Lab Med 2020 Jun 25. Epub 2020 Jun 25.

Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain.

Objectives Gaucher disease (GD) is the most common inherited lysosomal storage disease, caused by mutations in acid β-glucosidase (GBA) gene. This study aimed to identify mutations in Andalusia patients with GD and their genotype-phenotype correlation. Methods Descriptive observational study. Read More

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http://dx.doi.org/10.1515/cclm-2020-0306DOI Listing

Early evidence of delayed oligodendrocyte maturation in the mouse model of mucolipidosis type IV.

Dis Model Mech 2020 Jun 25. Epub 2020 Jun 25.

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA

Mucolipidosis type IV (MLIV) is a lysosomal disease caused by mutations in the gene that encodes the endolysosomal transient receptor potential channel mucolipin-1, or TRPML1. MLIV results in developmental delay, motor and cognitive impairments, and vision loss. Brain abnormalities include thinning and malformation of the corpus callosum, white matter abnormalities, accumulation of undegraded intracellular "storage" material and cerebellar atrophy in older patients. Read More

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http://dx.doi.org/10.1242/dmm.044230DOI Listing

Stratification of Fabry mutations in clinical practice: a closer look at α-galactosidase A-3D structure.

J Intern Med 2020 Jun 24. Epub 2020 Jun 24.

From the, Department of Neurology, University of Würzburg, Würzburg, Germany.

Background: Fabry disease (FD) is an X-linked lysosomal storage and multi-system disorder due to mutations in the α-galactosidase A (α-GalA) gene. We investigated the impact of individual amino acid exchanges in the α-GalA 3D-structure on the clinical phenotype of FD patients.

Patients And Methods: We enrolled 80 adult FD patients with α-GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α-GalA 3D-structure: patients with active site mutations, buried mutations and other mutations. Read More

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http://dx.doi.org/10.1111/joim.13125DOI Listing

LRRK2-Related Parkinson's Disease Due to Altered Endolysosomal Biology With Variable Lewy Body Pathology: A Hypothesis.

Front Neurosci 2020 4;14:556. Epub 2020 Jun 4.

Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States.

Mutations in the gene encoding for leucine-rich repeat kinase 2 (LRRK2) are associated with both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large protein comprised of a GTPase and a kinase domain. All pathogenic variants converge on enhancing LRRK2 kinase substrate phosphorylation, and distinct LRRK2 kinase inhibitors are currently in various stages of clinical trials. Read More

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http://dx.doi.org/10.3389/fnins.2020.00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287096PMC

A Case with Neonatal-onset Type 2 Neuronal Ceroid Lipofuscinosis: A Novel Mutation.

J Coll Physicians Surg Pak 2020 May;30(5):543-544

Department of Pediatrics, Faculty of Medicine, Division of Pediatric Neurology, İzmir Kâtip Çelebi University, İzmir, Turkey.

Neuronal ceroid lipofuscinosis (NCL) is a lysosomal storage disorder that causes progressive neurodegenerative disease as a result of storage in neurons and other cells. Late infantile type (NCL Type 2) of NCL, which is the most common neurodegenerative disease in childhood, is characterised by a homozygous mutation in the tripeptidyl peptidase-1 (TPP-1) gene. A male infant was referred to our neonatal intensive care unit (NICU) on 26th day of life with a diagnosis of metabolic disease. Read More

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http://dx.doi.org/10.29271/jcpsp.2020.05.543DOI Listing

Hearing loss in patients with mucopolysaccharidoses-1 and -6 after hematopoietic cell transplantation: A longitudinal analysis.

J Inherit Metab Dis 2020 Jun 24. Epub 2020 Jun 24.

Sylvia Toth Center for Multidisciplinary Follow up after Hematopoietic Cell Transplantation, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Hearing loss is frequently seen in mucopolysaccharidoses (MPS) patients. Although hematopoietic cell transplantation (HCT) increases overall survival, disease progression is observed in certain tissues. This study describes the course of hearing loss (HL) over time in transplanted MPS patients. Read More

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http://dx.doi.org/10.1002/jimd.12277DOI Listing

[The long-term follow-up of enzyme replacement treatment in late onset Pompe disease].

Ideggyogy Sz 2020 05;73(05-06):151-159

Nemzeti Egészségbiztosítási Alapkezelô, Budapest.

Pompe disease (PD) is a rare lysosomal disease caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the GAA gene. The enzymatic deficiency leads to the accumulation of glycogen within the lysosomes. Clinically, the disease has been classically classified in infantile and childhood/adult forms. Read More

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http://dx.doi.org/10.18071/isz.73.0151DOI Listing

Gene therapy targeting the inner retina rescues the retinal phenotype in a mouse model of CLN3 Batten disease.

Hum Gene Ther 2020 Jun 24. Epub 2020 Jun 24.

Institute of Ophthalmology, Molecular Therapy, London, United Kingdom of Great Britain and Northern Ireland.

The neuronal ceroid lipofuscinoses (NCLs), often referred to as Batten disease, are inherited lysosomal storage disorders that represent the most common neurodegeneration during childhood. Symptoms include seizures, vision loss, motor and cognitive decline and premature death. The development of brain-directed treatments for NCLs has made noteworthy progress in recent years. Read More

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http://dx.doi.org/10.1089/hum.2020.038DOI Listing

The contribution of copper efflux transporters ATP7A and ATP7B to chemoresistance and personalized medicine in ovarian cancer.

Biomed Pharmacother 2020 Jun 19;129:110401. Epub 2020 Jun 19.

Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. Electronic address:

Ovarian cancer has the highest mortality rate among all gynecologic cancers, with most patients presenting with advanced stage tumors. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time up to 80 % of others develop chemoresistance, rendering recurrent disease incurable. Moreover, according to latest EMSO-ESGO (European Society for Medical Oncology - European Society for Gynecological Oncology) consensus conference manuscript on ovarian cancer, there are currently no validated molecular predictive biomarkers for platinum resistance. Read More

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http://dx.doi.org/10.1016/j.biopha.2020.110401DOI Listing

Nephropathic cystinosis: an update on genetic conditioning.

Authors:
Rezan Topaloglu

Pediatr Nephrol 2020 Jun 20. Epub 2020 Jun 20.

Department of Pediatric Nephrology, School of Medicine, Hacettepe University, Ankara, Turkey.

Cystinosis is an autosomal recessive lysosomal storage disorder caused by CTNS gene mutations. The CTNS gene encodes the protein cystinosin, which transports free cystine from lysosomes to cytoplasm. In cases of cystinosin deficiency, free cystine accumulates in lysosomes and forms toxic crystals that lead to tissue and organ damage. Read More

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http://dx.doi.org/10.1007/s00467-020-04638-9DOI Listing

Fabry disease during the COVID-19 pandemic. Why and how treatment should be continued.

Authors:
Juan Politei

Mol Genet Metab 2020 Jun 6. Epub 2020 Jun 6.

Fundation for the Study of Neurometabolic Diseases, FESEN, Argentina. Electronic address:

Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include acroparesthesia, anhydrosis and angiokeratoma, which may present during childhood followed by cardiac, cerebral and renal complications. Even though pulmonary involvement is not widely appreciated by clinicians, an obstructive lung disease is another recognized component of Fabry disease. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274950PMC

Novel biomarkers for lysosomal storage disorders: Metabolomic and proteomic approaches.

Clin Chim Acta 2020 Jun 17;509:195-209. Epub 2020 Jun 17.

Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Lysosomal storage disorders (LSDs) are characterized by the accumulation of specific disease substrates inside the lysosomes of various cells, eventually leading to the deterioration of cellular function and multisystem organ damage. With the continuous discovery and validation of novel and advanced therapies for most LSDs, there is an urgent need to discover more versatile and clinically relevant biomarkers. The utility of these biomarkers should ideally extend beyond the screening and diagnosis of LSDs to the evaluation of disease severity and monitoring of therapy. Read More

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http://dx.doi.org/10.1016/j.cca.2020.06.028DOI Listing

Placental Findings in Lysosomal Storage Disease Diagnosis: A Case Report of Galactosialidosis.

Case Rep Pathol 2020 30;2020:8181056. Epub 2020 May 30.

Department of Pathology, UZA, Wilrijkstraat 10, 2650 Edegem, Belgium.

. Lysosomal storage disorders (LSDs) are rare diseases with more than 50 different entities described today. The spectrum of phenotypes varies from severe to lethal and early-onset disease to mild and late onset. Read More

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http://dx.doi.org/10.1155/2020/8181056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277025PMC

Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism.

Int J Mol Sci 2020 Jun 12;21(12). Epub 2020 Jun 12.

Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.

Mucopolysaccharidoses (MPSs) are inherited disorders of the glycosaminoglycan (GAG) metabolism. The defective digestion of GAGs within the intralysosomal compartment of affected patients leads to a broad spectrum of clinical manifestations ranging from cardiovascular disease to neurological impairment. The molecular mechanisms underlying the progression of the disease downstream of the genetic mutation of genes encoding for lysosomal enzymes still remain unclear. Read More

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http://dx.doi.org/10.3390/ijms21124211DOI Listing

Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice.

Lipids 2020 Jun 14. Epub 2020 Jun 14.

Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA, 90502, USA.

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Read More

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http://dx.doi.org/10.1002/lipd.12261DOI Listing

Chemical inhibition of β-glucocerebrosidase does not affect phagocytosis and early containment of Leishmania by murine macrophages.

Exp Parasitol 2020 Jun 12;216:107939. Epub 2020 Jun 12.

Cell Activation and Gene Expression Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; Departamento de Ciências Médicas, Universidade de Aveiro, Aveiro, Portugal. Electronic address:

Gaucher disease is a lysosomal storage disease in which a genetic deficiency in β-glucocerebrosidase leads to the accumulation of glycosphingolipids in lysosomes. Macrophages are amongst the cells most severely affected in Gaucher disease patients. One phenotype associated with Gaucher macrophages is the impaired capacity to fight bacterial infections. Read More

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http://dx.doi.org/10.1016/j.exppara.2020.107939DOI Listing

Cell-based no-wash fluorescence assays for compound screens using a fluorescence cytometry plate reader.

J Pharmacol Exp Ther 2020 Jun 12. Epub 2020 Jun 12.

National Institutes of Health.

High-throughput cell-based fluorescent imaging assays often require removal of background fluorescent signal to obtain robust measurements. Processing high density microplates to remove background signal is challenging due to equipment requirements and increasing variation after multiple plate wash steps. Here, we present the development of a wash-free cell-based fluorescence assay method for high-throughput screening (HTS) using a laser scanning fluorescence plate cytometer. Read More

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http://dx.doi.org/10.1124/jpet.120.265207DOI Listing

Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?

Am Heart J 2020 Apr 18;226:114-126. Epub 2020 Apr 18.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3Bs PT Government Associate Laboratory, Braga/Guimarães, Portugal.

Background: Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM.

Methods: Multicenter study including 780 patients with the ESC definition of HCM. Read More

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http://dx.doi.org/10.1016/j.ahj.2020.04.006DOI Listing

Lysosomal storage diseases: current therapies and future alternatives.

J Mol Med (Berl) 2020 Jul 11;98(7):931-946. Epub 2020 Jun 11.

Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Cra. 7 No. 43-82 Building 54, Room 305A, Bogotá D.C, 110231, Colombia.

Lysosomal storage disorders (LSDs) are a group of monogenic diseases characterized by progressive accumulation of undegraded substrates into the lysosome, due to mutations in genes that encode for proteins involved in normal lysosomal function. In recent years, several approaches have been explored to find effective and successful therapies, including enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, hematopoietic stem cell transplantation, and gene therapy. In the case of gene therapy, genome editing technologies have opened new horizons to accelerate the development of novel treatment alternatives for LSD patients. Read More

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http://dx.doi.org/10.1007/s00109-020-01935-6DOI Listing

Finding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: Opportunities for shared therapeutic interventions.

Biochim Biophys Acta Mol Basis Dis 2020 Jun 6;1866(10):165875. Epub 2020 Jun 6.

Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address:

Lysosomal storage disorders (LSDs) are diseases characterized by the accumulation of macromolecules in the late endocytic system and are caused by inherited defects in genes that encode mainly lysosomal enzymes or transmembrane lysosomal proteins. Niemann-Pick type C disease (NPCD), a LSD characterized by liver damage and progressive neurodegeneration that leads to early death, is caused by mutations in the genes encoding the NPC1 or NPC2 proteins. Both proteins are involved in the transport of cholesterol from the late endosomal compartment to the rest of the cell. Read More

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http://dx.doi.org/10.1016/j.bbadis.2020.165875DOI Listing

Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon in .

G3 (Bethesda) 2020 Jun 9. Epub 2020 Jun 9.

University of Missouri.

A neutered male domestic medium-haired cat presented at a veterinary neurology clinic at 20 months of age due to progressive neurological signs that included visual impairment, focal myoclonus, and frequent severe generalized seizures that were refractory to treatment with phenobarbital. Magnetic resonance imaging revealed diffuse global brain atrophy. Due to the severity and frequency of its seizures, the cat was euthanized at 22 months of age. Read More

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http://dx.doi.org/10.1534/g3.120.401407DOI Listing

The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases.

Cells 2020 Jun 5;9(6). Epub 2020 Jun 5.

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

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Read More

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http://dx.doi.org/10.3390/cells9061411DOI Listing