2,322 results match your criteria Neuronal Ceroid Lipofuscinoses

Drug-induced hyperthermia with rhabdomyolysis in CLN3 disease.

Eur J Paediatr Neurol 2022 Jun 11;39:74-78. Epub 2022 Jun 11.

Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Pediatrics, Gothenburg, Sweden. Electronic address:

CLN3 disease (MIM# 204200), the most prevalent of the neuronal ceroid lipofuscinoses (NCL), is an autosomal recessive disorder with juvenile onset characterized by blindness, epilepsy, dementia, psychiatric manifestations, and motor deterioration. Problems related to behavior, emotions and thought are among the main features. Antidepressant and antipsychotic drugs have been employed with variable results. Read More

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Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease.

Cells 2022 Jun 4;11(11). Epub 2022 Jun 4.

Molecular Medicine-IRCCS Stella Maris, 56128 Pisa, Italy.

CLN5 disease (MIM: 256731) represents a rare late-infantile form of neuronal ceroid lipofuscinosis (NCL), caused by mutations in the gene that encodes the CLN5 protein (CLN5p), whose physiological roles stay unanswered. No cure is currently available for CLN5 patients and the opportunities for therapies are lagging. The role of lysosomes in the neuro-pathophysiology of CLN5 disease represents an important topic since lysosomal proteins are directly involved in the primary mechanisms of neuronal injury occurring in various NCL forms. Read More

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Acidified drinking water attenuates motor deficits and brain pathology in a mouse model of a childhood neurodegenerative disorder.

Sci Rep 2022 May 30;12(1):9025. Epub 2022 May 30.

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

We recently demonstrated that HCl-acidified drinking water, which is widely used in laboratory animal facilities, had some beneficial effects in the Cln3 mouse model of juvenile Batten disease, a neurodegenerative lysosomal storage disorder. Here we tested if acidified drinking water has therapeutic effects in Cln1 nonsense mutant mice, a model of the infantile form of Batten disease. In Cln1 mice, acidified drinking water received from weaning prevented the impairment in pole climbing ability measured at 3 and 6 months of age. Read More

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Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.

Int J Mol Sci 2022 May 20;23(10). Epub 2022 May 20.

Pediatric Neurology Department, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland.

Neuronal ceroid lipofuscinoses (NCLs) are a group of rare, inherited, neurodegenerative lysosomal storage disorders that affect children and adults. They are traditionally grouped together, based on shared clinical symptoms and pathological ground. To date, 13 autosomal recessive gene variants, as well as one autosomal dominant gene variant, of NCL have been described. Read More

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Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia.

Int J Mol Sci 2022 May 17;23(10). Epub 2022 May 17.

Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China.

Infantile neuronal ceroid lipofuscinosis (INCL), the most severe form of neuronal ceroid lipofuscinoses, is caused by mutations in the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). Typical symptoms of this disease include progressive psychomotor developmental retardation, visual failure, seizures, and premature death. Here, we investigated seizure activity and relevant pathological changes in PPT1 knock-in mice (PPT1 KI). Read More

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Towards Understanding Behaviour and Emotions of Children with CLN3 Disease (Batten Disease): Patterns, Problems and Support for Child and Family.

Int J Environ Res Public Health 2022 05 12;19(10). Epub 2022 May 12.

Faculty of Behavioural and Movement Science, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands.

The juvenile variant of Neuronal Ceroid Lipofuscinosis (CLN3 disease/Batten disease) is a rare progressive brain disease in children and young adults, characterized by vision loss, decline in cognitive and motor capacities and epilepsy. Children with CLN3 disease often show disturbed behaviour and emotions. The aim of this study is to gain a better understanding of the behaviour and emotions of children with CLN3 disease and to examine the support that the children and their parents are receiving. Read More

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CNS-associated T-lymphocytes in a mouse model of Hereditary Spastic Paraplegia type 11 (SPG11) are therapeutic targets for established immunomodulators.

Exp Neurol 2022 May 20;355:114119. Epub 2022 May 20.

Section of Developmental Neurobiology, Department of Neurology, University Hospital, Würzburg, 97080, Würzburg, Germany. Electronic address:

Pharmacological targeting of neuroinflammation in distinct models of genetically mediated disorders of the central nervous system (CNS) has been shown to attenuate disease outcome significantly. These include mouse models mimicking distinct subtypes of neuronal ceroid lipofuscinoses (NCL, CLN diseases) as well as hereditary spastic paraplegia type 2 (HSP/SPG2). We here show in a model of another, complicated HSP form (SPG11) that there is neuroinflammation in distinct compartments of the diseased CNS. Read More

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Contribution of Mendelian disorders in a population-based pediatric neurodegeneration cohort.

J Pediatr 2022 May 13. Epub 2022 May 13.

Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. Electronic address:

Objective: To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients.

Study Design: Patients enrolled in the Center for Applied Genomics (CAG) Biobank at the Children's Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected ICD9 and ICD10 codes. A manual chart review was then performed to abstract detailed clinical information. Read More

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Experimental Therapeutic Approaches for the Treatment of Retinal Pathology in Neuronal Ceroid Lipofuscinoses.

Front Neurol 2022 18;13:866983. Epub 2022 Apr 18.

University Children's [email protected], University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The neuronal ceroid lipofuscinoses (NCLs) are a group of childhood-onset neurodegenerative lysosomal storage disorders mainly affecting the brain and the retina. In the NCLs, disease-causing mutations in 13 different ceroid lipofuscinoses genes (CLN) have been identified. The clinical symptoms include seizures, progressive neurological decline, deterioration of motor and language skills, and dementia resulting in premature death. Read More

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Clinical and genetic characterization of a cohort of 97 CLN6 patients tested at a single center.

Orphanet J Rare Dis 2022 05 3;17(1):179. Epub 2022 May 3.

Centogene GmbH, Am Strande 7, 18057, Rostock, Germany.

Background: Ceroid lipofuscinoses neuronal 6 (CLN6) disease belongs to the neuronal ceroid lipofuscinoses (NCLs), complex and genetically heterogeneous disorders with wide geographical and phenotypic variation. The first clinical signs usually appear between 18 months and 8 years, but examples of later-onset have also been reported. Common manifestations include ataxia, seizures, vision impairment, and developmental regression. Read More

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A man with epilepsy, bradykinesia, and cognitive decline.

Neurol Sci 2022 Apr 28. Epub 2022 Apr 28.

Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, 400016, Chongqing, China.

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Contribution of Whole-Genome Sequencing and Transcript Analysis to Decipher Retinal Diseases Associated with Variants.

Int J Mol Sci 2022 Apr 13;23(8). Epub 2022 Apr 13.

Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, F-59000 Lille, France.

Biallelic gene defects in are not only a cause of the late-infantile form of neuronal ceroid lipofuscinosis, but also of rare isolated retinal degeneration. We report clinical and genetic data of seven patients compound heterozygous or homozygous for variants in , issued from a French cohort with inherited retinal degeneration, and two additional patients retrieved from a Swiss cohort. Next-generation sequencing of large panels combined with whole-genome sequencing allowed for the identification of twelve variants from which seven were novel. Read More

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Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs.

Gene 2022 Jul 18;830:146513. Epub 2022 Apr 18.

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

A progressive neurological disorder was identified in purebred Dalmatian dogs. The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Read More

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Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.

Front Neurol 2022 4;13:886567. Epub 2022 Apr 4.

Pediatric Storage Disorders Laboratory, Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Read More

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The Unified Batten Disease Rating Scale (UBDRS): Validation and reliability in an independent CLN3 disease sample.

Eur J Paediatr Neurol 2022 May 4;38:62-65. Epub 2022 Apr 4.

Department of Neurology, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA.

Background: The neuronal ceroid lipofuscinoses (NCLs) are a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment. Together, NCLs represent the most common cause of cerebral neurodegenerative disease in children. CLN3 disease, the classic juvenile-onset form (JNCL) due to mutations in CLN3, is characterized by progressive vision loss, epilepsy, dementia, behavioral difficulties, and motor impairment. Read More

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Characterization of neurological disease progression in a canine model of CLN5 neuronal ceroid lipofuscinosis.

Dev Neurobiol 2022 05 28;82(4):326-344. Epub 2022 Apr 28.

Neurodegenerative Diseases Research Laboratory, University of Missouri, Columbia, Missouri, USA.

Golden Retriever dogs with a frameshift variant in CLN5 (c.934_935delAG) suffer from a progressive neurodegenerative disorder analogous to the CLN5 form of neuronal ceroid lipofuscinosis (NCL). Five littermate puppies homozygous for the deletion allele were identified prior to the onset of disease signs. Read More

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Cln5 represents a new type of cysteine-based -depalmitoylase linked to neurodegeneration.

Sci Adv 2022 04 15;8(15):eabj8633. Epub 2022 Apr 15.

Department of Pediatric Neurology, University Children's Hospital Zürich, University of Zurich, Steinwiesstrasse 75, 8032 Zürich, Switzerland.

Genetic variants are associated with childhood neurodegeneration and Alzheimer's disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (-depalmitoylation) activity using fluorescent substrates. Read More

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Aggregation chimeras provide evidence of in vivo intercellular correction in ovine CLN6 neuronal ceroid lipofuscinosis (Batten disease).

PLoS One 2022 11;17(4):e0261544. Epub 2022 Apr 11.

Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, Canterbury, New Zealand.

The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are fatal, mainly childhood, inherited neurodegenerative lysosomal storage diseases. Sheep affected with a CLN6 form display progressive regionally defined glial activation and subsequent neurodegeneration, indicating that neuroinflammation may be causative of pathogenesis. In this study, aggregation chimeras were generated from homozygous unaffected normal and CLN6 affected sheep embryos, resulting in seven chimeric animals with varied proportions of normal to affected cells. Read More

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Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function.

PLoS Biol 2022 03 31;20(3):e3001590. Epub 2022 Mar 31.

Departments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.

Loss-of-function mutations in the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) cause neuronal ceroid lipofuscinosis (NCL), a devastating neurodegenerative disease. The substrates of PPT1 are largely undescribed, posing a limitation on molecular dissection of disease mechanisms and therapeutic development. Here, we provide a resource identifying >100 novel PPT1 substrates. Read More

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Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders.

Mol Omics 2022 05 11;18(4):256-278. Epub 2022 May 11.

Department of Chemistry, University of Illinois at Chicago, USA.

The major function of the lysosome is to degrade unwanted materials such as lipids, proteins, and nucleic acids; therefore, deficits of the lysosomal system can result in improper degradation and trafficking of these biomolecules. Diseases associated with lysosomal failure can be lethal and are termed lysosomal storage disorders (LSDs), which affect 1 in 5000 live births collectively. LSDs are inherited metabolic diseases caused by mutations in single lysosomal and non-lysosomal proteins and resulting in the subsequent accumulation of macromolecules within. Read More

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Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models.

Autophagy 2022 May 28;18(5):1127-1151. Epub 2022 Apr 28.

Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (Fau), Erlangen, Germany.

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagy as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. Read More

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Neurophysiological Findings in Neuronal Ceroid Lipofuscinoses.

Front Neurol 2022 25;13:845877. Epub 2022 Feb 25.

Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.

Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of neurodegenerative diseases, characterized by progressive cerebral atrophy due to lysosomal storage disorder. Common clinical features include epileptic seizures, progressive cognitive and motor decline, and visual failure, which occur over different time courses according to subtypes. During the latest years, many advances have been done in the field of targeted treatments, and in the next future, gene therapies and enzyme replacement treatments may be available for several NCL variants. Read More

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February 2022

Natural history of retinal degeneration in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses.

Sci Rep 2022 03 7;12(1):3670. Epub 2022 Mar 7.

Faculty of Agriculture and Life Sciences, Lincoln University, PO Box 85084, Lincoln, Canterbury, 7647, New Zealand.

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases with a common set of symptoms including cognitive and motor decline and vision loss. Naturally occurring sheep models of CLN5 and CLN6 disease display the key clinical features of NCL, including a progressive loss of vision. We assessed retinal histology, astrogliosis, and lysosomal storage accumulation in CLN5 affected (CLN5) and CLN6 affected (CLN6) sheep eyes and age-matched controls at 3, 6, 12, and 18 months of age to determine the onset and progression of retinal pathology in NCL sheep. Read More

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Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).

Front Cell Dev Biol 2022 16;10:812728. Epub 2022 Feb 16.

Department of Biology, Trent University, Peterborough, ON, Canada.

The neuronal ceroid lipofuscinoses (NCLs), also referred to as Batten disease, are a family of neurodegenerative diseases that affect all age groups and ethnicities around the globe. At least a dozen NCL subtypes have been identified that are each linked to a mutation in a distinct ceroid lipofuscinosis neuronal () gene. Mutations in genes cause the accumulation of autofluorescent lipoprotein aggregates, called ceroid lipofuscin, in neurons and other cell types outside the central nervous system. Read More

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February 2022

CLN7 gene therapy: hope for an ultra-rare condition.

J Clin Invest 2022 03;132(5)

CLN7 Batten disease, also known as variant late infantile neuronal ceroid lipofuscinosis type 7 (vLINCL7), is an ultra-rare form of Batten disease that presents early in life with severe neurological symptoms, including visual deficits, motor problems, and frequent seizures. There is high unmet need for disease-modifying therapies, as no existing treatment can halt progression or prevent premature death. In this issue of the JCI, Chen et al. Read More

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A Novel, Apparently Silent Variant in Causes Neuronal Ceroid Lipofuscinosis with Marked Intrafamilial Variability.

Int J Mol Sci 2022 Feb 18;23(4). Epub 2022 Feb 18.

Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany.

Variants in can cause neuronal ceroid lipofuscinoses (NCLs) as well as nonsyndromic retinopathy. The mutation spectrum includes mainly missense and stop variants, but splice sites and frameshift variants have also been reported. To date, apparently synonymous substitutions have not been shown to cause -associated diseases. Read More

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February 2022

: A Model System for Neurological Disorders.

Cells 2022 01 28;11(3). Epub 2022 Jan 28.

Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora 3086, Australia.

Background: The incidence of neurological disorders is increasing due to population growth and extended life expectancy. Despite advances in the understanding of these disorders, curative strategies for treatment have not yet eventuated. In part, this is due to the complexities of the disorders and a lack of identification of their specific underlying pathologies. Read More

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January 2022

Case Report: Novel MFSD8 Variants in a Chinese Family With Neuronal Ceroid Lipofuscinoses 7.

Front Genet 2022 26;13:807515. Epub 2022 Jan 26.

Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, China.

Neuronal ceroid lipofuscinoses (NCLs) are among the most common progressive encephalopathies of childhood. Neuronal ceroid lipofuscinosis 7 (CLN7), one of the late infantile-onset NCLs, is an autosomal recessive disorder caused by mutations in the gene on chromosome 4q28. Almost all reported mutations of in CLN7 patients were SNVs. Read More

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January 2022

Ppt1-deficiency dysregulates lysosomal Ca homeostasis contributing to pathogenesis in a mouse model of CLN1 disease.

J Inherit Metab Dis 2022 05 17;45(3):635-656. Epub 2022 Mar 17.

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

Inactivating mutations in the PPT1 gene encoding palmitoyl-protein thioesterase-1 (PPT1) underlie the CLN1 disease, a devastating neurodegenerative lysosomal storage disorder. The mechanism of pathogenesis underlying CLN1 disease has remained elusive. PPT1 is a lysosomal enzyme, which catalyzes the removal of palmitate from S-palmitoylated proteins (constituents of ceroid lipofuscin) facilitating their degradation and clearance by lysosomal hydrolases. Read More

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Higher order visual dysfunction and myoclonic-atonic seizure: an atypical presentation of CLN6 neuronal ceroid lipofuscinosis.

BMJ Case Rep 2022 Feb 9;15(2). Epub 2022 Feb 9.

Neuromedicine, Institute of Postgraduate Medical Education and Research Bangur Institute of Neurology, Kolkata, West Bengal, India

Neuronal ceroid lipofuscinosis is a rare childhood neurodegenerative disease, classified under the spectrum of progressive myoclonic epilepsy (PME). Cognitive decline, seizures including myoclonus, vision loss and ataxia are the commonly described manifestations of this illness. While visual failure in this disease is largely attributed to retinal, macular degeneration and optic atrophy, with this index case, we report an atypical presentation in the form of higher order visual dysfunction. Read More

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February 2022