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Ophthalmic Genet 2019 Apr 22:1-5. Epub 2019 Apr 22.

a Genetics Research Center , University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.

Background: Cone-rod dystrophies are a group of genetically and phenotypically heterogeneous inherited degenerative retinal diseases primarily affecting macular and cone system function. MFSD8 loss-of-function variants are mainly related to the variant late-infantile neuronal ceroid lipofuscinoses which present with progressive motor and mental regression in combination with seizures, ataxia, and visual impairment.

Material And Methods: Clinical examination and genomic DNA extraction were collected from two unrelated Iranian families presenting with autosomal recessive cone-rod dystrophy. Read More

ASN Neuro 2019 Jan-Dec;11:1759091419843393

1 Department of Pediatrics, Biological Sciences Division, The University of Chicago, IL, USA.

In humans, homozygous mutations in the TPP1 gene results in loss of tripeptidyl peptidase 1 (TPP1) enzymatic activity, leading to late infantile neuronal ceroid lipofuscinoses disease. Using a mouse model that targets the Tpp1 gene and recapitulates the pathology and clinical features of the human disease, we analyzed end-stage (4 months) transcriptional changes associated with lack of TPP1 activity. Using RNA sequencing technology, Tpp1 expression changes in the forebrain/midbrain and cerebellum of 4-month-old homozygotes were compared with strain-related controls. Read More

Adv Healthc Mater 2019 Apr 18:e1801271. Epub 2019 Apr 18.

Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. Read More

Mol Genet Metab 2019 Mar 27. Epub 2019 Mar 27.

Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Read More

Neuromolecular Med 2019 Mar 27. Epub 2019 Mar 27.

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders caused by mutations in fourteen distinct ceroid lipofuscinoses, neuronal (CLN) genes described with various severe symptoms such as seizures, visual failure, motor decline, and progressive cognitive deterioration. The current research represents novel CLN5 (c.741G > A) and CLN8 (c. Read More

CNS Drugs 2019 Apr;33(4):315-325

Department of Pediatrics, Section Biochemistry, University Medical Center Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epilepsy, loss of vision, motor disturbances, and early death. While various therapeutic strategies are currently being explored as treatment options for these fatal disorders, there is presently only one clinically approved drug that has been shown to effectively attenuate the progression of a specific form of neuronal ceroid lipofuscinosis, CLN2 disease (cerliponase alfa, a lysosomal enzyme infused into the brain ventricles of patients with CLN2 disease). Read More

Nat Rev Neurol 2019 Mar;15(3):161-178

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Batten disease (also known as neuronal ceroid lipofuscinoses) constitutes a family of devastating lysosomal storage disorders that collectively represent the most common inherited paediatric neurodegenerative disorders worldwide. Batten disease can result from mutations in 1 of 13 genes. These mutations lead to a group of diseases with loosely overlapping symptoms and pathology. Read More

Clin Chim Acta 2019 May 13;492:69-71. Epub 2019 Feb 13.

Metabolic Laboratory, Center of Diagnostics, Hamburg, Germany; NCL Clinic, Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany. Electronic address:

Purpose: CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. CLN2 disease has recently become treatable by enzyme replacement, which can only be effective when the disease is diagnosed early. We have investigated the reliability of a test for TPP1 deficiency in dried blood specimens (DBS) to detect CLN2 disease. Read More

Ann Transl Med 2018 Dec;6(24):476

Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that are caused for the most part by enzyme deficiencies within the lysosome resulting in accumulation of undegraded substrate. This storage process leads to a broad spectrum of clinical manifestations depending on the specific substrate and site of accumulation. Examples of LSDs include the mucopolysaccharidoses, mucolipidoses, oligosaccharidoses, Pompe disease, Gaucher disease, Fabry disease, the Niemann-Pick disorders, and neuronal ceroid lipofuscinoses. Read More

Cells 2019 Feb 2;8(2). Epub 2019 Feb 2.

Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2, Canada.

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. Read More

Orphanet J Rare Dis 2019 01 21;14(1):19. Epub 2019 Jan 21.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Background: CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression.

Results: A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Read More

Sci Rep 2019 Jan 17;9(1):151. Epub 2019 Jan 17.

Division of Biology, Kansas State University, Manhattan, KS, 66506, USA.

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN5 deficiency causes a subtype of NCL, referred to as CLN5 disease. CLN5 is a soluble lysosomal protein with an unclear function in the cell. Read More

Mol Neurodegener 2019 01 16;14(1). Epub 2019 Jan 16.

Section on Developmental Genetics, Program on Endocrinology and Molecular Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland, 20892-1830, USA.

Neuronal Ceroid Lipofuscinoses (NCLs), commonly known as Batten disease, constitute a group of the most prevalent neurodegenerative lysosomal storage disorders (LSDs). Mutations in at least 13 different genes (called CLNs) cause various forms of NCLs. Clinically, the NCLs manifest early impairment of vision, progressive decline in cognitive and motor functions, seizures and a shortened lifespan. Read More

BMC Neurol 2018 Dec 12;18(1):203. Epub 2018 Dec 12.

FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, Gujarat, 380015, India.

Background: Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively. Till date, nearly 76 mutations in PPT1 and approximately 140 mutations, including large deletion/duplications, in TPP1 genes have been reported in the literature. The present study includes 34 unrelated Indian patients (12 females and 22 males) having epilepsy, visual impairment, cerebral atrophy, and cerebellar atrophy. Read More

Ann Clin Transl Neurol 2018 Nov 14;5(11):1385-1393. Epub 2018 Oct 14.

Department of Neuropathology Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Germany.

Objective: The neuronal ceroid lipofuscinoses (NCL) are genetic degenerative disorders of brain and retina. NCL with juvenile onset (JNCL) is genetically heterogeneous but most frequently caused by mutations of CLN3. Classical juvenile CLN3 includes a rare protracted form, which has previously been linked to autophagic vacuolar myopathy (AVM). Read More

Lancet Neurol 2019 Jan 21;18(1):107-116. Epub 2018 Nov 21.

UCL Institute of Ophthalmology, University College London, London, UK.

Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect children. Diagnosis has improved with the use of comprehensive DNA-based tests that simultaneously screen for many genes. The identification of disease-causing mutations in 13 genes provides a basis for understanding the molecular mechanisms underlying neuronal ceroid lipofuscinoses, and for the development of targeted therapies. Read More

Biochim Biophys Acta Mol Basis Dis 2019 Feb 16;1865(2):322-328. Epub 2018 Nov 16.

Division of Biology, Kansas State University, Manhattan, KS 66506, USA; Graduate Biochemistry Group, Kansas State University, Manhattan, Kansas 66506, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN8 deficiency causes a subtype of NCL, referred to as CLN8 disease. CLN8 is an ER resident protein with unknown function; however, a role in ceramide metabolism has been suggested. Read More

Doc Ophthalmol 2019 02 16;138(1):55-70. Epub 2018 Nov 16.

Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia.

Purpose: Mutation of the CLN3 gene, associated with juvenile neuronal ceroid lipofuscinosis, has recently been associated with late-onset, non-syndromic retinal dystrophy. Herein we describe the multimodal imaging, immunological and systemic features of an adult with compound heterozygous CLN3 mutations.

Methods: A 50-year-old female with non-syndromic retinal dystrophy from the age of 36 years underwent multimodal retinal imaging, electroretinography, neuroimaging, immunological studies and genetic testing. Read More

Nat Cell Biol 2018 12 5;20(12):1370-1377. Epub 2018 Nov 5.

Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.

Organelle biogenesis requires proper transport of proteins from their site of synthesis to their target subcellular compartment. Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and traffic through the Golgi complex before being transferred to the endolysosomal system, but how they are transferred from the ER to the Golgi is unknown. Here, we show that ER-to-Golgi transfer of lysosomal enzymes requires CLN8, an ER-associated membrane protein whose loss of function leads to the lysosomal storage disorder, neuronal ceroid lipofuscinosis 8 (a type of Batten disease). Read More

Cells 2018 Oct 29;7(11). Epub 2018 Oct 29.

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

Despite the increased focus on the role of calcium in the neuronal ceroid lipofuscinoses (NCLs, also known as Batten disease), links between calcium signalling and the proteins associated with the disease remain to be identified. A central protein in calcium signalling is calmodulin (CaM), which regulates many of the same cellular processes affected in the NCLs. In this study, we show that 11 of the 13 NCL proteins contain putative CaM-binding domains (CaMBDs). Read More

Biochim Biophys Acta Mol Basis Dis 2018 11 11;1864(11):3559-3573. Epub 2018 Aug 11.

Department of Biology, Trent University, Peterborough, Ontario, Canada. Electronic address:

Mutations in CLN3 cause a juvenile form of neuronal ceroid lipofuscinosis (NCL), commonly known as Batten disease. Currently, there is no cure for NCL and the mechanisms underlying the disease are not well understood. In the social amoeba Dictyostelium discoideum, the CLN3 homolog, Cln3, localizes predominantly to the contractile vacuole (CV) system. Read More

Ann Clin Transl Neurol 2018 Sep 14;5(9):1089-1103. Epub 2018 Aug 14.

Department of Biochemistry and Molecular Genetics American University of Beirut Medical Center Beirut Lebanon.

Objective: Neuronal Ceroid Lipofuscinoses (NCL) are fatal inherited neurodegenerative diseases with established neuronal cell death and increased ceramide levels in brain, hence, a need for disease-modifying drug candidates, with potential to enhance growth, reduce apoptosis and lower ceramide in neuronal precursor PC12 cells and human NCL cell lines using enhanced flupirtine aromatic carbamate derivatives in vitro.

Methods: Aromatic carbamate derivatives were tested by establishing growth curves under pro-apoptotic conditions and activity evaluated by trypan blue and JC-1 staining, as well as a drop in pro-apoptotic ceramide in neuronal precursor PC12 cells following siRNA knockdown of the gene, and CLN1-/CLN2-/CLN3-/CLN6-/CLN8 patient-derived lymphoblasts. Ceramide levels were determined in CLN1-/CLN2-/CLN3-/CLN6-/CLN8 patient-derived lymphoblasts before and after treatment. Read More

J Med Case Rep 2018 Sep 25;12(1):281. Epub 2018 Sep 25.

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

Background: The neuronal ceroid lipofuscinoses are a group of neurodegenerative, lysosomal storage disorders. They are inherited as an autosomal recessive pattern with the exception of adult neuronal ceroid lipofuscinosis, which can be inherited in either an autosomal recessive or an autosomal dominant manner. The neuronal ceroid lipofuscinoses are characterized by accumulation of autofluorescent lipopigments in the cells and one of the most important pathological manifestations is ceroid accumulation in the lysosomes. Read More

Mol Neurodegener 2018 09 4;13(1):48. Epub 2018 Sep 4.

Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.

Background: Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes. Read More

BMC Med Genet 2018 08 25;19(1):151. Epub 2018 Aug 25.

Institute of Biomedical Chemistry, Pogodinskaya street 10 building 8, 119121, Moscow, Russia.

Background: Neuronal ceroid lipofuscinoses (NCLs) are the most common autosomal recessive neurodegenerative disorders in children. Clinical manifestations include progressive cognitive decline, motor impairment, ataxia, visual loss, seizures and early death. To date more than 440 NCL-causing mutations in 13 genes are known. Read More

Brain Behav 2018 Sep 23;8(9):e01096. Epub 2018 Aug 23.

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

Introduction: The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal neurodegenerative lysosomal storage diseases of children caused by various mutations in a range of genes. Forms associated with mutations in two of these, CLN5 and CLN6, are being investigated in well-established sheep models. Brain atrophy leading to psychomotor degeneration is among the defining features, as is regional progressive ossification of the inner cranium. Read More

Lancet Child Adolesc Health 2018 08 2;2(8):547-548. Epub 2018 Jul 2.

Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address:

Acta Neuropathol Commun 2018 08 8;6(1):74. Epub 2018 Aug 8.

Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, 5 Cutcombe Road, London, SE5 9RX, UK.

The neuronal ceroid lipofuscinoses (NCLs) are the most common cause of childhood dementia and are invariably fatal. Early localized glial activation occurs in these disorders, and accurately predicts where neuronal loss is most pronounced. Recent evidence suggests that glial dysfunction may contribute to neuron loss, and we have now explored this possibility in infantile NCL (INCL, CLN1 disease). Read More

PLoS One 2018 7;13(8):e0201470. Epub 2018 Aug 7.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota, United States of America.

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Read More

Mol Ther 2018 Oct 17;26(10):2366-2378. Epub 2018 Jul 17.

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

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are neurodegenerative lysosomal storage diseases predominantly affecting children. Single administration of brain-directed lentiviral or recombinant single-stranded adeno-associated virus 9 (ssAAV9) vectors expressing ovine CLN5 into six pre-clinically affected sheep with a naturally occurring CLN5 NCL resulted in long-term disease attenuation. Treatment efficacy was demonstrated by non-invasive longitudinal in vivo monitoring developed to align with assessments used in human medicine. Read More

Zhonghua Er Ke Za Zhi 2018 Aug;56(8):601-604

Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.

To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis. The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents. Read More

Clin Chim Acta 2018 Nov 24;486:151-155. Epub 2018 Jul 24.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong. Electronic address:

Background: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is a hereditary progressive neurodegenerative disease well documented among Caucasians, but such clinical data and genetic characterization is lacking among Asian populations.

Patient And Methods: A 13-year-old Chinese girl presented for diagnostic evaluation with retinitis pigmentosa, generalised tonic-clonic seizure and cerebellar ataxia. Electron microscopy of whole blood and skin biopsy, and mutation analysis of CLN3 gene with genomic DNA and cDNA, were performed. Read More

Biochim Biophys Acta Mol Cell Res 2018 Jul 23;1865(10):1437-1450. Epub 2018 Jul 23.

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

Mutations in CLN5 cause neuronal ceroid lipofuscinosis (NCL), a currently untreatable neurodegenerative disorder commonly known as Batten disease. Several genetic models have been generated to study the function of CLN5, but one limitation has been the lack of a homolog in lower eukaryotic model systems. Our previous work revealed a homolog of CLN5 in the social amoeba Dictyostelium discoideum. Read More

Dis Model Mech 2018 09 5;11(9). Epub 2018 Sep 5.

Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, 50931 Cologne, Germany

Juvenile neuronal ceroid lipofuscinosis (jNCL) is a rare but fatal inherited lysosomal storage disorder mainly affecting children. The disease is caused by mutations in the gene that lead to the accumulation of storage material in many tissues, prominent immune responses and neuronal degeneration. One of the first symptoms is vision loss followed by motor dysfunction and mental decline. Read More

Mol Syst Biol 2018 07 11;14(7):e8071. Epub 2018 Jul 11.

Neuroproteomics, Max Delbrück Center for Molecular Medicine and Berlin Institute of Health, Berlin, Germany

Information on protein-protein interactions (PPIs) is of critical importance for studying complex biological systems and developing therapeutic strategies. Here, we present a double-readout bioluminescence-based two-hybrid technology, termed LuTHy, which provides two quantitative scores in one experimental procedure when testing binary interactions. PPIs are first monitored in cells by quantification of bioluminescence resonance energy transfer (BRET) and, following cell lysis, are again quantitatively assessed by luminescence-based co-precipitation (LuC). Read More

Expert Opin Biol Ther 2018 07 2;18(7):755-764. Epub 2018 Jul 2.

a Department of Neurosurgery , Emory University , Atlanta , GA , USA.

Introduction: The neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases (LSDs) that cause myoclonic epilepsy, loss of cognitive and motor function, degeneration of the retina leading to blindness, and early death. Most are caused by loss-of-function mutations in either lysosomal proteins or transmembrane proteins. Current therapies are supportive in nature. Read More

Mol Cell Neurosci 2018 10 1;92:17-26. Epub 2018 Jun 1.

Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA. Electronic address:

Loss-of-function mutations in ATP13A2 are associated with three neurodegenerative diseases: a rare form of Parkinson's disease termed Kufor-Rakeb syndrome (KRS), a lysosomal storage disorder termed neuronal ceroid lipofuscinosis (NCL), and a form of hereditary spastic paraplegia (HSP). Furthermore, recent data suggests that heterozygous carriers of mutations in ATP13A2 may confer risk for the development of Parkinson's disease, similar to the association of mutations in glucocerebrosidase (GBA) with both Parkinson's disease and Gaucher's disease, a lysosomal storage disorder. Mutations in ATP13A2 are generally thought to be loss of function; however, the lack of human autopsy tissue has prevented the field from determining the pathological consequences of losing functional ATP13A2. Read More

eNeuro 2018 Mar-Apr;5(2). Epub 2018 May 17.

Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. Read More

Epilepsy Res 2018 08 16;144:49-52. Epub 2018 May 16.

Department of Neurology, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina. Electronic address:

Purpose: The objective of the study was to describe the initial clinical and electroencephalographic findings in children with late-infantile neuronal ceroid lipofuscinosis (LINCL).

Method: The clinical charts of 35 patients seen between 1990 and 2016 were reviewed. The patients were divided into two groups: Group 1 (G1) consisting of 12 patients with NCL type 2 (CLN2) disease confirmed by enzymatic activity in dried blood spots on filter paper and/or genetic studies, and Group 2 (G2) consisting of 23 patients with a diagnosis of LINCL based on pathology studies by muscle biopsy. Read More

Adv Exp Med Biol 2018 ;1074:91-99

UCL Institute of Ophthalmology, Department of Genetics & NIHR BRC at Moorfields Eye Hospital, London, UK.

Neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, inherited lysosomal storage disorders mostly affecting the central nervous system of children. Symptoms include vision loss, seizures, motor deterioration and cognitive decline ultimately resulting in premature death. Studies in animal models showed that the diseases are amenable to gene supplementation therapies, and over the last decade, major advances have been made in the (pre)clinical development of these therapies. Read More

N Engl J Med 2018 05 24;378(20):1898-1907. Epub 2018 Apr 24.

From the Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (A.S., A.K.); BioMarin Pharmaceutical, Novato, CA (T.A., H.C., P.S., D.J.); the Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome (N.S.); Nationwide Children's Hospital and Ohio State University, Columbus (E.L.R.); UCL Great Ormond Street Institute of Child Health, London (P.G.); and the Citigroup Biomedical Imaging Center, Departments of Radiology and Genetic Medicine, Weill Cornell Medical College, New York (D.B., J.P.D.).

Background: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.

Methods: In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years. Treatment was initiated at a dose of 30 mg, 100 mg, or 300 mg; all the patients then received the 300-mg dose for at least 96 weeks. Read More

Neurobiol Dis 2018 Jul 13;115:182-193. Epub 2018 Apr 13.

The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Pathology & Laboratory Medicine, Philadelphia, PA 19104, United States. Electronic address:

The neuronal ceroid lipofuscinoses are a class of inherited neurodegenerative diseases characterized by the accumulation of autofluorescent storage material. The most common neuronal ceroid lipofuscinosis has juvenile onset with rapid onset blindness and progressive degeneration of cognitive processes. The juvenile form is caused by mutations in the CLN3 gene, which encodes the protein CLN3. Read More

Medicine (Baltimore) 2018 Apr;97(15):e0299

Department of Neurology and Neuroscience Center, The First Hospital of JiLin University, Changchun.

Introduction: Progressive myoclonic epilepsy (PME) is rare epilepsy syndrome. Although EEG is a useful neurophysiological technique in the evaluation of epilepsy, few EEG abnormalities have been described in PME. So, how to use EEG hints to establish the suspected diagnosis of PME as soon as possible should be addressed. Read More

Front Aging Neurosci 2018 26;10:79. Epub 2018 Mar 26.

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Collaborative Innovation Center for Brain Science, Xiamen University, Xiamen, China.

The retromer complex and associated sorting nexins (SNXs) comprise a critical trafficking machinery which mediates endosomal protein sorting. Retromer and/or SNX dysfunction has been linked to several neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS). In AD, deficiency of the retromer complex or its cargo proteins impairs endosomal trafficking of amyloid precursor protein (APP), resulting in the overproduction of β-amyloid (Aβ). Read More

Orphanet J Rare Dis 2018 04 10;13(1):54. Epub 2018 Apr 10.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, 20892, USA.

Background: Infantile and late infantile neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases affecting the central nervous system (CNS). The infantile NCL (INCL) is caused by mutations in the PPT1 gene and late-infantile NCL (LINCL) is due to mutations in the TPP1 gene. Deficiency in PPT1 or TPP1 enzyme function results in lysosomal accumulation of pathological lipofuscin-like material in the patient cells. Read More

Mol Ther 2018 05 2;26(5):1343-1353. Epub 2018 Mar 2.

Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, City Road, London EC1V 2PD, UK. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. Read More

Mol Genet Metab 2018 05 19;124(1):64-70. Epub 2018 Mar 19.

Advanced Clinical Research Center, Institute of Neurological Disorder, Kanagawa, Japan; Jikei University School of Medicine, Tokyo, Japan. Electronic address:

We first characterized PPT1 and TPP1 enzymes in dried blood spots (DBS), plasma/serum, and leukocytes/lymphocytes using neuronal ceroid lipofuscinosis (NCL) 1 and 2 patients and control subjects. PPT1 enzyme had only one acid form in control DBS, plasma/serum, and leukocytes/lymphocytes and showed deficient activities in these samples from NCL 1 patients. Conversely, TPP1 enzymes in control DBS and leukocytes/lymphocytes consisted of two forms, an acidic form and a neutral form, whereas serum TPP1 enzyme had only a neutral form. Read More

Rev Neurol 2018 Mar;66(S01):S17-S23

Hospital de Ninos Doctor Ricardo Gutierrez, Buenos Aires, Argentina.

Introduction: Autism spectrum disorders are neurodevelopmental dysfunctions that are characterised by deficits in social integration and communication, associated with restricted interests and stereotypic behaviour. A high percentage are related to language disorders, sensory dysfunctions, attention deficit disorder, bipolarity, intellectual disability or epilepsy, among other comorbidities. It is estimated that around 30% of children with autism, with typical early development, may present regression in the first years of life, which was already reported by Kanner in one of his original cases. Read More

Hum Mol Genet 2018 05;27(10):1711-1722

Section Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Defects in the MFSD8 gene encoding the lysosomal membrane protein CLN7 lead to CLN7 disease, a neurodegenerative lysosomal storage disorder belonging to the group of neuronal ceroid lipofuscinoses. Here, we have performed a SILAC-based quantitative analysis of the lysosomal proteome using Cln7-deficient mouse embryonic fibroblasts (MEFs) from a Cln7 knockout (ko) mouse model. From 3335 different proteins identified, we detected 56 soluble lysosomal proteins and 29 highly abundant lysosomal membrane proteins. Read More

Can J Neurol Sci 2018 03;45(2):150-157

3Department of Medicine (Geriatric Medicine and Neurology),Dalhousie University,Halifax,Nova Scotia,Canada.

Objective: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. Read More