2,198 results match your criteria Neuronal Ceroid Lipofuscinoses


Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder.

Eur J Med Genet 2021 Jun 11:104259. Epub 2021 Jun 11.

Murdoch Children's Research Institute, The Royal Children's Hospital, Victoria, Australia; Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia. Electronic address:

RNA sequencing (RNAseq) is emerging as a complementary tool to DNA sequencing, providing utility in diagnosis for disorders such as neuronal ceroid lipofuscinosis CLN2 disease. We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391. Read More

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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

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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

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The neuronal ceroid lipofuscinosis-related protein CLN8 regulates endo-lysosomal dynamics and dendritic morphology.

Biol Cell 2021 May 22. Epub 2021 May 22.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones Médicas "Mercedes y Martin Ferreyra"- IMMF-UNC-CONICET, Laboratorio de Neurobiología, Av. Friuli 2434, 5016 Córdoba, Argentina, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina.

Background Information: The endo-lysosomal system (ELS) comprises a set of membranous organelles responsible for transporting intracellular and extracellular components within cells. Defects in lysosomal proteins usually affect a large variety of processes and underlie many diseases, most of them with a strong neuronal impact. Mutations in the endoplasmic reticulum-resident CLN8 protein cause CLN8 disease. Read More

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Evolution of the retinal function by flash-ERG in one child suffering from neuronal ceroid lipofuscinosis CLN2 treated with cerliponase alpha: case report.

Doc Ophthalmol 2021 May 6. Epub 2021 May 6.

Service des Explorations Fonctionnelles, Hôpital Robert Debré, AP-HP, Paris, France.

Introduction: Neuronal ceroid lipofuscinoses (CLN) are neurodegenerative disorders among the most frequent, inherited as an autosomal recessive trait. Affected patients can present with progressive decline in cognitive and motor functions, seizures, a shortened life span and visual deficiency. CLN2 is one of the rare CLN that benefits from treatment by cerliponase alpha an enzyme replacement therapy. Read More

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Intravitreal gene therapy protects against retinal dysfunction and degeneration in sheep with CLN5 Batten disease.

Exp Eye Res 2021 Jun 28;207:108600. Epub 2021 Apr 28.

Faculty of Agricultural and Life Sciences, Lincoln University, Lincoln, 7647, New Zealand; Department of Radiology, University of Otago, Christchurch, 8140, New Zealand. Electronic address:

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases primarily affecting children. A common feature across most NCLs is the progressive loss of vision. We performed intravitreal injections of self-complementary AAV9 vectors packaged with either ovine CLN5 or CLN6 into one eye of 3-month-old CLN5 or CLN6 animals, respectively. Read More

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The converging roles of Batten disease proteins in neurodegeneration and cancer.

iScience 2021 Apr 19;24(4):102337. Epub 2021 Mar 19.

Department of Biology, Trent University, Peterborough, ON K9L 0G2, Canada.

Epidemiological studies have reported an inverse correlation between cancer and neurodegenerative disorders, and increasing evidence shows that similar genes and pathways are dysregulated in both diseases but in a contrasting manner. Given the genetic convergence of the neuronal ceroid lipofuscinoses (NCLs), a family of rare neurodegenerative disorders commonly known as Batten disease, and other neurodegenerative diseases, we sought to explore the relationship between cancer and the NCLs. In this review, we survey data from The Cancer Genome Atlas and available literature on the roles of NCL genes in different oncogenic processes to reveal links between all the NCL genes and cancer-related processes. Read More

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A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses.

Acta Neurol Belg 2021 Jun 30;121(3):737-748. Epub 2021 Mar 30.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Mutations in CLN3 (OMIM: 607042) are associated with juvenile neuronal ceroid lipofuscinoses (JNCL)-a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration. The study aimed to determine the underlying genetic factors justifying the NCL phenotype in a large Iraqi consanguineous family. Four affected individuals with an initial diagnosis of NCL were recruited. Read More

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Cathepsin D Variants Associated With Neurodegenerative Diseases Show Dysregulated Functionality and Modified α-Synuclein Degradation Properties.

Front Cell Dev Biol 2021 11;9:581805. Epub 2021 Feb 11.

Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.

Cathepsin D (CTSD) is a lysosomal protease important for the degradation of various substrates, including disease-associated proteins like α-synuclein (a-syn), amyloid precursor protein (APP) and tau, all of which tend to aggregate if not efficiently degraded. Hence, it is not surprising that genetic variants within the gene have been linked to neurodegenerative diseases, like Parkinson's and Alzheimer's disease (PD, AD), as well as the lysosomal storage disorder neuronal ceroid lipofuscinosis type-10 (NCL10). Although recent studies have shown the molecular dependence of substrate degradation via CTSD within autophagic pathways, only little is known about the precise role of lysosomal CTSD function in disease development. Read More

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February 2021

Characterizing upper limb function in the context of activities of daily living in CLN3 disease.

Am J Med Genet A 2021 05 8;185(5):1399-1413. Epub 2021 Feb 8.

Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

In CLN3 disease, impairments in motor function are frequently reported to have later onset compared to visual and cognitive decline, but upper limb motor function has yet to be explored in this population. In a cohort of 22 individuals with CLN3, we used a novel application of multiple measures to (1) characterize motor function, particularly of the upper limbs, in activities of daily living (ADLs), and (2) explore associations between motor function and age as well as visual ability, disease severity, and cognitive function, as evaluated by the Unified Batten Disease Rating Scale (UBDRS), a validated CLN3 disease measure. ADLs that required coordination, speed, and fine motor control were particularly challenging for children with CLN3 based on item-level performance across direct assessments (Jebsen-Taylor Hand Function Test [JTHFT] and MyoSet Tools) and caregiver reports (Pediatric Evaluation of Disability Inventory-Computer Adaptive Testing [PEDI-CAT] and Patient-Reported Outcomes Measurement Information System [PROMIS] Pediatric Upper Extremity). Read More

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[Neuronal ceroid lipofuscinoses].

Ophthalmologe 2021 02 4;118(2):96-97. Epub 2021 Feb 4.

Klinik und Poliklinik für Augenheilkunde, Experimentelle Ophthalmologie, Universitätsklinikum Hamburg-Eppendorf (UKE), Martinistr. 52, 20246, Hamburg, Deutschland.

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February 2021

Urine proteomics analysis of patients with neuronal ceroid lipofuscinoses.

iScience 2021 Feb 31;24(2):102020. Epub 2020 Dec 31.

Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Unit, Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.

The neuronal ceroid lipofuscinoses (NCL) are a group of 13 rare neurodegenerative disorders characterized by accumulation of cellular storage bodies. There are few therapeutic options, and existing tests do not monitor disease progression and treatment response. However, urine biomarkers could address this need. Read More

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February 2021

Neuronal ceroid lipofuscinosis: genetic and phenotypic spectrum of 14 patients from Turkey.

Neurol Sci 2021 Mar 23;42(3):1103-1111. Epub 2021 Jan 23.

Clinical Chemistry Department, Ege University Faculty of Medicine, İzmir, Turkey.

Introduction And Purpose: Neuronal ceroid lipofuscinoses (NCLs) is a group of congenital metabolic diseases where the neurodegenerative process with the accumulation of ceroid and lipofuscin autofluorescent storage materials is at the forefront. According to the age of presentation, NCLs are classified as congenital, infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) NCLs. In our study, it was aimed to discuss the clinical and molecular characteristics of our patients diagnosed with NCL. Read More

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[Neuroinflammation in neuronal ceroid lipofuscinosis].

Authors:
V Behnke T Langmann

Ophthalmologe 2021 Feb 7;118(2):98-105. Epub 2021 Jan 7.

Lehrstuhl für Experimentelle Immunologie des Auges, Zentrum für Augenheilkunde, Medizinische Fakultät und Uniklinik Köln, Joseph-Stelzmann-Str. 9, 50931, Köln, Deutschland.

Background: Retinal degeneration and neuroinflammation are often early hallmarks of different subtypes of neuronal ceroid lipofuscinosis (NCL) in patients and genetic animal models.

Objective: This article gives a summary of recently published research articles and novel concepts in the field of NCL-related neuroinflammation.

Material And Methods: A search was carried out in PubMed for relevant publications and the results as well as own NCL-related research are discussed. Read More

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February 2021

Revealing the clinical phenotype of atypical neuronal ceroid lipofuscinosis type 2 disease: Insights from the largest cohort in the world.

J Paediatr Child Health 2021 04 30;57(4):519-525. Epub 2020 Dec 30.

UCL MRC Laboratory for Molecular Cell Biology and UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Aim: Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme, leading to progressive deterioration of neurological functions commonly occurring in children aged 2-4 years and culminating in early death. Atypical cases associated with earlier or later symptom onset, or even protracted course, have already been reported. Such variable manifestations may constitute an additional challenge to early diagnosis and initiation of appropriate treatment. Read More

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An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease.

J Neurochem 2021 05 16;157(3):764-780. Epub 2021 Jan 16.

Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation of auto-fluorescent storage material in lysosomes, NCLs are largely characterised by region-specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations in the extracellular environment-making the secretome an area of significant interest. Read More

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Status dystonicus associated with CLN8 disease.

Brain Dev 2021 Apr 24;43(4):571-575. Epub 2020 Dec 24.

Department of Pediatrics, Konya Research and Training Hospital, Konya, Turkey.

Background: Status dystonicus is an underdiagnosed condition, probably due to heterogeneous etiology, presentation and course. Herein, we report the first case of CLN8 disease in the literature presenting with status dystonicus who responded well to pharmacological intervention.

Case: A boy aged five years and three months presented with fever, loss of appetite, intermittent excessive dystonic contractions, opisthotonus with retrocollis, and irritability for three days. Read More

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Cerliponase alfa changes the natural history of children with neuronal ceroid lipofuscinosis type 2: The first French cohort.

Eur J Paediatr Neurol 2021 Jan 8;30:17-21. Epub 2020 Dec 8.

Service of Paediatric Neurology, Centre for Inherited Metabolic Diseases, University Hospital of Marseille, Hôpital Timone Enfants, 278 Rue Saint-Pierre, 13005, Marseille, France.

Introduction: Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution: cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa. Read More

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January 2021

Macula as a Window to Diagnosis.

J Pediatr 2021 04 15;231:284-285. Epub 2020 Dec 15.

Department of Neuropathology, National Institute of Mental Health and Neurosciences, Karnataka, India.

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[Ophthalmological manifestations of neuronal ceroid lipofuscinoses (NCL) : NCL as diseases of brain and retina-the role of ophthalmologists].

Ophthalmologe 2021 Feb;118(2):113-118

Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.

Background: Neuronal ceroid lipofuscinoses are hereditary lysosomal storage diseases, which lead to a progressive neurodegeneration of the brain and retina. Visual loss can be the initial symptom but can also occur later in the course of the disease.

Objective: The aim of this article is to provide ophthalmologists with an overview of the characteristic ocular alterations and the general disease course of the 13 currently known various forms of NCL. Read More

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February 2021

Enzymatic diagnosis of neuronal lipofuscinoses in dried blood spots using substrates for concomitant tandem mass spectrometry and fluorimetry.

J Mass Spectrom 2021 Jan 13;56(1):e4675. Epub 2020 Dec 13.

Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry, Mass Spectrometry Laboratory, Marktstrasse 29, Ruesselsheim am Main, D-65428, Germany.

Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative diseases predominantly in childhood that are characterized by psychomotor deterioration, epilepsy, and early death of patients. The NCLs analyzed in the present study are caused by defects of the specific enzymes, CLN1 (palmitoyl protein thioesterase 1; PPT1), CLN2 (tripeptidyl peptidase 1; TPP1), and CLN10 (cathepsin D). Specific and sensitive diagnostic assays of NCLs were the main goal of this study. Read More

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January 2021

Neurofilament light chain levels correlate with clinical measures in CLN3 disease.

Genet Med 2021 04 26;23(4):751-757. Epub 2020 Nov 26.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.

Purpose: CLN3 disease is a neurodegenerative disorder with onset in childhood. It affects multiple functions at different developmental stages. Incomplete understanding of the pathophysiology hampers identification of cell and tissue biochemical compounds reflective of the disease process. Read More

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Current Insights in Elucidation of Possible Molecular Mechanisms of the Juvenile Form of Batten Disease.

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

Laboratory of Mechanisms of Gene Expression, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.

The neuronal ceroid lipofuscinoses (NCLs) collectively constitute one of the most common forms of inherited childhood-onset neurodegenerative disorders. They form a heterogeneous group of incurable lysosomal storage diseases that lead to blindness, motor deterioration, epilepsy, and dementia. Traditionally the NCL diseases were classified according to the age of disease onset (infantile, late-infantile, juvenile, and adult forms), with at least 13 different NCL varieties having been described at present. Read More

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October 2020

Batten disease: an expert update on agents in preclinical and clinical trials.

Expert Opin Investig Drugs 2020 Dec 1;29(12):1317-1322. Epub 2020 Nov 1.

University of Rochester Division of Child Neurology, Box 631, University of Rochester Medical Center , Rochester, NY, USA.

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December 2020

Sex- and region-biased depletion of microglia/macrophages attenuates CLN1 disease in mice.

J Neuroinflammation 2020 Oct 28;17(1):323. Epub 2020 Oct 28.

Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg, Würzburg, Germany.

Background: The neuronal ceroid lipofuscinoses (CLN diseases) are fatal lysosomal storage diseases causing neurodegeneration in the CNS. We have previously shown that neuroinflammation comprising innate and adaptive immune reactions drives axonal damage and neuron loss in the CNS of palmitoyl protein thioesterase 1-deficient (Ppt1) mice, a model of the infantile form of the diseases (CLN1). Therefore, we here explore whether pharmacological targeting of innate immune cells modifies disease outcome in CLN1 mice. Read More

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October 2020

An iPSC-Derived Neuron Model of CLN3 Disease Facilitates Small Molecule Phenotypic Screening.

ACS Pharmacol Transl Sci 2020 Oct 1;3(5):931-947. Epub 2020 Sep 1.

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

The neuronal ceroid lipofuscinoses (NCLs) are a family of rare lysosomal storage disorders. The most common form of NCL occurs in children harboring a mutation in the gene. This form is lethal with no existing cure or treatment beyond symptomatic relief. Read More

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October 2020

[Experimental therapeutic approaches for the treatment of retinal dystrophy in neuronal ceroid lipofuscinosis].

Ophthalmologe 2021 Feb;118(2):106-112

Klinik und Poliklinik für Augenheilkunde, Experimentelle Ophthalmologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.

Background: Neuronal ceroid lipofuscinosis (NCL) is a group of rare and fatal neurodegenerative lysosomal storage diseases. Progressive retinal degeneration and loss of vision are among the characteristic symptoms of affected patients. A brain-directed enzyme replacement therapy has been shown to significantly attenuate the neurological symptoms in CLN2 patients and is currently the only approved therapy for NCL; however, there is presently no treatment option for retinal dystrophy in NCL. Read More

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February 2021

Moyamoya and progressive myoclonic epilepsy secondary to bi-allelic mutations - A previously unreported association.

Epilepsy Behav Rep 2020 31;14:100389. Epub 2020 Aug 31.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.

The neuronal ceroid lipofuscinoses (NCL) are a collection of lysosomal storage diseases characterised by the accumulation of characteristic inclusions containing lipofuscin in various tissues of the body and are one of the causes of progressive myoclonic epilepsy. Mutations in at least thirteen genes have been identified as causes of NCL, which can present as infantile, late-infantile, juvenile or adult forms. codes for an endoplasmic reticulum transmembrane protein of unknown function. Read More

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Functional Analysis of a Novel CLN5 Mutation Identified in a Patient With Neuronal Ceroid Lipofuscinosis.

Front Genet 2020 2;11:536221. Epub 2020 Sep 2.

Precision Medical Center, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive inherited neurodegenerative disorders mainly affecting children, and at least 13 causative genes ( to and to ) have been identified. Here, we reported a novel homozygous missense mutation (c.434G > C, p. Read More

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September 2020