30,635 results match your criteria Lysosomal Storage Disease


Wiad Lek 2021 ;74(4):1032-1036


At all ages, skeletal muscle weakness characterizes Pompe disease, causes mobility problems and affects the respiratory system. We aimed to provide a narrative review of terminology, etiology, epidemiology, clinical manifestations, complications, and prognosis of Pompe disease, supported with a clinical case presentation. The clinical manifestation and complications of Pompe disease are illustrated with the clinical case presentation of a late-onset form in a white child. Read More

View Article and Full-Text PDF

Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity.

Mol Genet Metab 2021 Jun 15. Epub 2021 Jun 15.

Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA, USA; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA, USA. Electronic address:

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. Read More

View Article and Full-Text PDF

Precision medicine in Fabry disease.

Nephrol Dial Transplant 2021 Jun;36(Supplement_2):14-23

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster, University Hospital Münster, Münster, Germany.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (GLA) gene, leading to a deficiency in α-galactosidase A. The lysosomal accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its deacylated form, globotriaosylsphingosine (lyso-Gb3), results in progressive renal failure, cardiomyopathy associated with cardiac arrhythmia and recurrent cerebrovascular events, significantly limiting life expectancy in affected patients. In male patients, a definitive diagnosis of FD involves demonstrating a GLA deficiency in leucocytes. Read More

View Article and Full-Text PDF

Longitudinal Data in Patients with Niemann-Pick Type C Disease Under Combined High Intrathecal and Low Intravenous Dose of 2-hydroxylpropyl-β-cyclodextrin.

Innov Clin Neurosci 2021 Jan-Mar;18(1-3):11-16. Epub 2021 Jan 1.

Drs. Bountouvi, Giorgi, Papadopoulou, Tsirouda, Fryganas, Spanou, Georgaki, Asprogeraka, and Dinopoulos are with the Third Department of Pediatrics, Athens University Medical School, at the University General Hospital "Attikon" in Athens, Greece.

Niemann-Pick Type C disease (NPC) is a rare, incurable, autosomal-recessive, lysosomal storage disorder with protean and progressive neurovisceral manifestations characterized by accumulation of intracellular unesterified cholesterol. The investigational use of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) in the treatment of NPC has shown promising results in improving life expectancy and reducing neurological damage in this patient population. This case report describes two children with the neurological form of NPC: a 5-year-old male patient in advanced stage of the disease and an 11-year-old female patient in moderately advanced stage. Read More

View Article and Full-Text PDF
January 2021

Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease.

Front Neurol 2021 4;12:679927. Epub 2021 Jun 4.

Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, United Kingdom.

Genetics has driven significant discoveries in the field of neurodegenerative diseases (NDDs). An emerging theme in neurodegeneration warrants an urgent and comprehensive update: that carrier status of early-onset autosomal recessive (AR) disease, typically considered benign, is associated with an increased risk of a spectrum of late-onset NDDs. () gene mutations, responsible for the AR lysosomal storage disorder Gaucher disease, are a prominent example of this principle, having been identified as an important genetic risk factor for Parkinson disease. Read More

View Article and Full-Text PDF

MPSBase: Comprehensive repository of differentially expressed genes for mucopolysaccharidoses.

Mol Genet Metab 2021 Jun 15. Epub 2021 Jun 15.

Cells, Tissues and Genes Laboratory, HCPA, Porto Alegre 90035903, Brazil; Bioinformatics Core, HCPA, Porto Alegre 90035903, Brazil; Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501970, Brazil; Department of Genetics, UFRGS, Porto Alegre 91501970, Brazil. Electronic address:

Mucopolysaccharidoses (MPS) are lysosomal storage diseases (LSDs) caused by the deficiency of enzymes essential for the metabolism of extracellular matrix components called glycosaminoglycans (GAGs). To understand the physiopathology and alterations due to the lysosomal accumulation resulting from enzymatic deficiencies and their secondary outcomes can improve the diagnosis and treatment of rare genetic diseases. This work presents a database for differentially expressed genes from different public MPS data. Read More

View Article and Full-Text PDF

Telemedicine and GM-2 gangliosidosis (Tay-Sachs) disease - A new savior on the horizon during COVID-19 pandemic.

Indian J Ophthalmol 2021 Jul;69(7):1955

Department of Vitreoretina, Sunetra Eye Care Centre, Ghaziabad, Uttar Pradesh, India.

View Article and Full-Text PDF

[Median nerve compression in the carpal tunnel in children - a delayed diagnosis. About 20 clinical cases].

Ann Chir Plast Esthet 2021 Jun 15. Epub 2021 Jun 15.

Service de chirurgie plastique et reconstructrice, Centre des Brûlés, CHU de Nantes, 1, place Alexis-Ricordeau, 44093 Nantes, France.

Objectives: The carpal tunnel syndrome is rare in children. We performed a retrospective study of 10 children. The aim is to show that the diagnosis of carpal tunnel syndrome is difficult in children. Read More

View Article and Full-Text PDF

Hepatocellular carcinoma as a complication of Niemann-Pick disease type C1.

Am J Med Genet A 2021 Jun 17. Epub 2021 Jun 17.

Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Niemann-Pick disease type C (NPC) is a rare and fatal lysosomal storage disorder characterized by neurodegeneration and hepatic involvement. Mutations in either NPC1 or NPC2, two genes encoding lysosomal proteins, lead to an intracellular accumulation of unesterified cholesterol and sphingolipids in late endosomes/lysosomes. Early cholestatic disease is considered a hallmark of patients with early disease onset. Read More

View Article and Full-Text PDF

Does administration of hydroxychloroquine/amiodarone accelerate accumulation of globotriaosylceramide and globotriaosylsphingosine in Fabry mice?

Mol Genet Metab Rep 2021 Sep 29;28:100773. Epub 2021 May 29.

Department of Functional Bioanalysis, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.

Drug-induced lysosomal storage disease (DILSD) caused by cationic amphiphilic drugs (CADs), which exhibits toxic manifestations and pathological findings mimicking Fabry disease (α-galactosidase A deficiency), has attracted the interests of clinicians and pathologists. Although the affected region is lysosomes in both the diseases, DILSD is characterized by intralysosomal accumulation of phospholipids and Fabry disease that of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3). However, it is unknown whether administration of CADs affects the catabolism of Gb3 and Lyso-Gb3 in Fabry disease. Read More

View Article and Full-Text PDF
September 2021

Gaucher disease: Identification and novel variants in Mexican and Spanish patients.

Arch Med Res 2021 Jun 13. Epub 2021 Jun 13.

Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, CMN-SXXI, IMSS, Ciudad de México, Méx. Electronic address:

Background: Gaucher disease (GD) is the most prevalent lysosomal storage disorder, affecting all ethnic groups, although its prevalence is higher in Ashkenazi Jewish populations. Three clinical forms of GD have been described: Type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute neuronopathic. An autosomal recessive disorder is caused by variants in the human glucocerebrosidase gene (GBA; MIM*606463) located on chromosome 1q21, resulting from deficit or lack of activity of the β-glucocerebrosidase enzyme, leading to the accumulation of glucocerebroside substrate in the cells of the macrophage-monocyte system. Read More

View Article and Full-Text PDF

X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay.

Clin Exp Nephrol 2021 Jun 14. Epub 2021 Jun 14.

Department of Nephrology, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Read More

View Article and Full-Text PDF

Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

View Article and Full-Text PDF

SARS-CoV-2 infection and COVID‒19 in Gaucher disease: indications for vaccination

László Maródi

Orv Hetil 2021 06 13;162(24):938-942. Epub 2021 Jun 13.

1 Semmelweis Egyetem, Általános Orvostudományi Kar, Bőr-, Nemikórtani és Dermatoonkológiai Klinika, Primer Immundeficiencia Klinikai Egység és Laboratórium, Budapest, Mária u. 41., 1085.

At the start of the pandemic caused by the novel coronavirus (SARS-CoV-2), the Gaucher disease community anticipated that infection with this emerging viral pathogen would be associated with high morbidity and mortality in individuals with this chronic metabolic disorder. Surprisingly, however, preliminary studies suggest that Gaucher disease does not confer a higher risk of severe, life-threatening effects of SARS-CoV-2 infection, and no severe cases have been reported in large cohorts of patients from the United States, Europe and Israel. It is thought that the accumulation of glucocerebroside in the cells of Gaucher patients may promote immune tolerance rather than inflammation on exposure to SARS-CoV-2. Read More

View Article and Full-Text PDF

A pathogenic HEXA missense variant in wild boars with Tay-Sachs disease.

Mol Genet Metab 2021 Jul 7;133(3):297-306. Epub 2021 May 7.

Department of Veterinary Science, University of Parma, Via Taglio, 8, 43100 Parma, Italy.

Gangliosidoses are inherited lysosomal storage disorders caused by reduced or absent activity of either a lysosomal enzyme involved in ganglioside catabolism, or an activator protein required for the proper activity of a ganglioside hydrolase, which results in the intra-lysosomal accumulation of undegraded metabolites. We hereby describe morphological, ultrastructural, biochemical and genetic features of GM2 gangliosidosis in three captive bred wild boar littermates. The piglets were kept in a partially-free range farm and presented progressive neurological signs, starting at 6 months of age. Read More

View Article and Full-Text PDF

Frequency of Fabry disease in a juvenile idiopathic arthritis cohort.

Pediatr Rheumatol Online J 2021 Jun 12;19(1):91. Epub 2021 Jun 12.

Rheumatology Unit, School of Medical Sciences and University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Background: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including in the musculoskeletal system. Read More

View Article and Full-Text PDF

UDP-GlcNAc-1-phosphotransferase is a clinically important regulator of human and mouse hair pigmentation.

J Invest Dermatol 2021 Jun 8. Epub 2021 Jun 8.

Centre for Dermatology Research, University of Manchester, UK; The NIHR Biomedical Research Centre, Manchester, UK;; Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA;; Monasterium Laboratory, Münster, Germany. Electronic address:

UDP-GlcNAc-1-phosphotransferase, a product of two separate genes (GNPTAB, GNPTG), is essential for sorting and transport of lysosomal enzymes to lysosomes. GNPTAB gene defects cause extracellular missorting of lysosomal enzymes resulting in lysosomal storage diseases, namely mucolipidosis (ML) type II, which is associated with hair discoloration. Yet, the physiological functions of GNPTAB in the control of hair follicle (HF) pigmentation remain unknown. Read More

View Article and Full-Text PDF

A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-β-cyclodextrin for acute liver disease in infants with Niemann-Pick C1.

Mol Genet Metab Rep 2021 Sep 26;28:100772. Epub 2021 May 26.

Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America.

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in -lysosomal storage of unesterified cholesterol in the central nervous system and liver. Acute liver disease in the newborn period may be self-limited or fatal. 2-hydroxypropyl-β-cyclodextrin (2HPBCD) is a cholesterol-binding agent that reduces lysosomal cholesterol storage. Read More

View Article and Full-Text PDF
September 2021

Trigger finger in children with hurler syndrome - distribution pattern and treatment options.

GMS Interdiscip Plast Reconstr Surg DGPW 2021 5;10:Doc04. Epub 2021 May 5.

Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany.

Mucopolysaccharidosis is a rare and congenital autosomal recessive lysosomal storage disorder of glycosaminoglycans. An enzyme defect leads to cell, tissue and organ dysfunction. Carpal tunnel syndrome and trigger finger are the results of mucopolysaccharid deposition. Read More

View Article and Full-Text PDF

Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders.

Nat Commun 2021 06 9;12(1):3495. Epub 2021 Jun 9.

Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy.

Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Read More

View Article and Full-Text PDF

Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.

PLoS One 2021 9;16(6):e0252325. Epub 2021 Jun 9.

The Michael J. Fox Foundation for Parkinson's Research, Grand Central Station, New York, New York, United States of America.

Multiple mutations have been described in the human GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase) that degrades glucosylceramide and is pivotal in glycosphingolipid substrate metabolism. Depletion of GCase, typically by homozygous mutations in GBA1, is linked to the lysosomal storage disorder Gaucher's disease (GD) and distinct or heterozygous mutations in GBA1 are associated with increased Parkinson's disease (PD) risk. While numerous genes have been linked to heritable PD, GBA1 mutations in aggregate are the single greatest risk factor for development of idiopathic PD. Read More

View Article and Full-Text PDF

Ocular Manifestations of Neuronal Ceroid Lipofuscinoses.

Semin Ophthalmol 2021 Jun 9:1-14. Epub 2021 Jun 9.

Department of Ophthalmology, Dayanand Medical College & Hospital, Ludhiana, India.

Neuronal ceroid lipofuscinoses (NCLs) are a group of rare neurodegenerative storage disorders associated with devastating visual prognosis, with an incidence of 1/1,000,000 in the United States and comparatively higher incidence in European countries. The pathophysiological mechanisms causing NCLs occur due to enzymatic or transmembrane defects in various sub-cellular organelles including lysosomes, endoplasmic reticulum, and cytoplasmic vesicles. NCLs are categorized into different types depending upon the underlying cause i. Read More

View Article and Full-Text PDF

[Diffuse parenchymal lung diseases in Niemann-Pick disease type C2].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):519-521

Department of Pulmonology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.

View Article and Full-Text PDF

[To improve the understanding of diagnosis and treatment of lysosomal storage diseases].

Y Liang X P Luo

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):435-438

Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

View Article and Full-Text PDF

More than tubular dysfunction: cystinosis and kidney outcomes.

J Nephrol 2021 Jun 7. Epub 2021 Jun 7.

Department of Pediatric Metabolism and Nutrition, Cukurova University Faculty of Medicine, Adana, Turkey.

Background: Cystinosis is a lysosomal storage disease that affects many tissues. Its prognosis depends predominantly on kidney involvement. Cystinosis has three clinical forms: nephropathic infantile, nephropathic juvenile and non-nephropathic adult. Read More

View Article and Full-Text PDF

Anderson-Fabry Disease: From Endothelial Dysfunction to Emerging Therapies.

Adv Pharmacol Pharm Sci 2021 13;2021:5548445. Epub 2021 May 13.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

The Anderson-Fabry disease is a rare, X-linked, multisystemic, progressive lysosomal storage disease caused by -galactosidase A total or partial deficiency. The resulting syndrome is mainly characterized by early-onset autonomic neuropathy and life-threatening multiorgan involvement, including renal insufficiency, heart disease, and early stroke. The enzyme deficiency leads to tissue accumulation of the glycosphingolipid globotriaosylceramide and its analogues, but the mechanisms linking such accumulation to organ damage are only partially understood. Read More

View Article and Full-Text PDF

Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice.

Front Mol Neurosci 2021 21;14:677895. Epub 2021 May 21.

NeuroGenCell, Institut du Cerveau et de la Moelle Épinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in both glial cells and neurons. MLD results from an inherited deficiency of arylsulfatase A (ARSA) and myelin degeneration in the central and peripheral nervous systems. Currently, no effective treatment is available for the most frequent late infantile (LI) form of MLD after symptom onset. Read More

View Article and Full-Text PDF

Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: A nationwide survey in Japan.

Mol Genet Metab 2021 Jul 12;133(3):277-288. Epub 2021 May 12.

Advanced Clinical Research Center, Southern Tohoku Research Center for Neuroscience, Kanagawa, Japan.

Introduction: Lysosomal storage disorders and peroxisomal disorders are rare diseases caused by the accumulation of substrates of the metabolic pathway within lysosomes and peroxisomes, respectively. Owing to the rarity of these diseases, the prevalence of lysosomal storage disorders and peroxisomal disorders in Japan is unknown. Therefore, we conducted a nationwide survey to estimate the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. Read More

View Article and Full-Text PDF