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Sphingolipid Metabolism Diseases ⁎ Thomas Kolter, Konrad Sandhoff
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1758 (2006) 2057–2079 www.elsevier.com/locate/bbamem Review Sphingolipid metabolism diseases ⁎ Thomas Kolter, Konrad Sandhoff Kekulé-Institut für Organische Chemie und Biochemie der Universität, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany Received 23 December 2005; received in revised form 26 April 2006; accepted 23 May 2006 Available online 14 June 2006 Abstract Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated “cross correction”, gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT. © 2006 Elsevier B.V. All rights reserved. Keywords: Ceramide; Lysosomal storage disease; Saposin; Sphingolipidose Contents 1. Sphingolipid structure, function and biosynthesis ..........................................2058 1.1. -
Retted Q&A: Epilepsy Incidence, Treatments and Research Dr. Eric
RettEd Q&A: Epilepsy Incidence, Treatments and Research Dr. Eric Marsh, MD PhD, Medical Director Rett Clinic, NHS Investigator, and Basic Scientist, Children’s Hospital of Philadelphia Webcast 09/11/2018 Facilitator: Paige Nues, Rettsyndrome.org Recording link: https://attendee.gotowebinar.com/recording/2303318923907771398 ATTENDEE QUESTIONS RESPONSE REFERENCES AED Questions: Treatments and Triggers I want to know what about relation between Stressors are anecdotally reported to lower the seizure pain, digestive pain, apnea and seizure threshold- these would all be stressful features that could discharge. lower seizure threshold and theoretically increase seizure frequency. Any opinions on fycompa? Very limited experience so far to make a clear judgment. I have tried it in 2 Rett patients without great success, both in patients with very severe seizures. Is there a way to tell the difference between There is a slide in the talk that goes over some features, such a seizure and a “Rett spell” other than EEG? as retained awareness, repetitive nature of the events, that can give some hints as to the nature of the event, but only EEG can definitively discern the difference. My daughter has epilepsy and always has Without knowing all of her clinical details, it is hard for me to seizures. She takes medication Onfi and give recommendations. Depending on seizure types, EEG, Keppra and still have seizures. What should and previous medications tried, I would suggest other meds I do? I need help and ideas thanks. such as Rufinamide, valproic acid or trying the ketogenic diet. Do you see seizures connected to puberty or You can look at Jane Lane’s RettEd about puberty. -
Communication Intervention in Rett Syndrome: a Systematic Review Research in Autism Spectrum Disorders
Research in Autism Spectrum Disorders 3 (2009) 304–318 Contents lists available at ScienceDirect Research in Autism Spectrum Disorders Journal homepage: http://ees.elsevier.com/RASD/default.asp Review Communication intervention in Rett syndrome: A systematic review Jeff Sigafoos a,*, Vanessa A. Green a, Ralf Schlosser b, Mark F. O’eilly c, Giulio E. Lancioni d, Mandy Rispoli c, Russell Lang c a Victoria University of Wellington, New Zealand b Northeastern University, Boston and Childrens Hospital Boston at Waltham, MA, USA c Meadows Center for Preventing Educational Risk, The University of Texas at Austin, Austin, TX, USA d University of Bari, Bari, Italy ARTICLE INFO ABSTRACT Article history: We reviewed communication intervention studies involving people Received 25 September 2008 with Rett syndrome. Systematic searches of five electronic databases, Accepted 26 September 2008 selected journals, and reference lists identified nine studies meeting the inclusion criteria. These studies were evaluated in terms of: (a) Keywords: participant characteristics, (b) target skills, (c) procedures, (d) main Communication intervention findings, and (e) certainty of evidence. Across the nine studies, Rett syndrome intervention was provided to a total of 31 participants aged 2:7–17:0 Systematic review (years:months). Communication modes included speech, gestures, communication boards, and computer-based systems. Targeted communication functions included imitative speech, requesting, naming/commenting, and various receptive language skills (e.g., respond to requests, answer questions, receptively identify symbols). Intervention approaches included early intensive behavioral inter- vention, systematic instruction, and music therapy. Positive out- comes were reported for 26 (84%) of the 31 participants. However, these outcomes must be interpreted with caution because the certainty of evidence was inconclusive for all but one of the studies. -
Disease Reference Book
The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia............................................................................................................................................................................................................................................................. -
Epilepsy and Rett Syndrome
EPILEPSY AND RETT SYNDROME Liisa Metsähonkala, Pediatric Neurologist Epilepsia-Helsinki, Helsinki University Hospital HUS Helsinki University Hospital RETT Epilepsy -syndrome Epilepsy in Epilepsy in Rett Rett syndrome syndrome Epilepsy may be a major or minor problem for people with Rett syndrome and their families 2 28.9.19 HUS Helsinki University Hospital EPILEPSY AND RETT SYNDROME - Some general aspects of epilepsy - Epilepsy in Rett syndrome (focus on children) - Diversity of epileptic seizures - Diversity of nonepileptic paroxysmal attacks - How to make the diagnosis? - Treatment of epilepsy 3 28.9.19 HUS Helsinki University Hospital WHAT IS EPILEPSY ? International - epilepsy is not one disease but a large group of different League disorders Against Epilepsy - an epileptic seizure is a transient occurrence of signs and/ or symptoms due to abnormal and certain kind of neuronal activity (excessive or synchronous) in the brain - versus nonepileptic symptoms - epilepsy is a disease characterized by an enduring predisposition to generate epileptic seizures – versus seizures that anyone can have because of an acute provoking factor 4 28.9.19 HUS Helsinki University Hospital Seizure types Etiology Focal Generalized Unknown onset onset onset Structural Genetic Epilepsy types Infectious Combined FocalFocal Generalized Unknown Generalized Metabolic & Focal Immune Co-morbidities Unknown Epilepsy Syndromes HUS Helsinki University Hospital Generalized seizures Focal seizures • Originate at some point within • Originate within networks and rapidly -
Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 6 April 2021 doi:10.20944/preprints202104.0161.v1 Review Sphingolipids and cell signaling: Relationship between health and disease in the central nervous system Andrés Felipe Leal1, Diego A. Suarez1,2, Olga Yaneth Echeverri-Peña1, Sonia Luz Albarracín3, Carlos Javier Alméciga-Díaz1*, Angela Johana Espejo-Mojica1* 1 Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C., 110231, Colombia; [email protected] (A.F.L.), [email protected] (D.A.S.), [email protected] (O.Y.E.P.) 2 Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C., Colombia; [email protected] (D.A.S.) 3 Nutrition and Biochemistry Department, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C., Colombia; [email protected] (S.L.A.) * Correspondence: [email protected]; Tel.: +57-1-3208320 (Ext 4140) (C.J.A-D.). [email protected]; Tel.: +57-1-3208320 (Ext 4099) (A.J.E.M.) Abstract Sphingolipids are lipids derived from an 18-carbons unsaturated amino alcohol, the sphingosine. Ceramide, sphingomyelins, sphingosine-1-phosphates, gangliosides and globosides, are part of this group of lipids that participate in important cellular roles such as structural part of plasmatic and organelle membranes maintaining their function and integrity, cell signaling response, cell growth, cell cycle, cell death, inflammation, cell migration and differentiation, autophagy, angiogenesis, immune system. The metabolism of these lipids involves a broad and complex network of reactions that convert one lipid into others through different specialized enzymes. Impairment of sphingolipids metabolism has been associated with several disorders, from several lysosomal storage diseases, known as sphingolipidoses, to polygenic diseases such as diabetes and Parkinson and Alzheimer diseases. -
GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies
International Journal of Molecular Sciences Review GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies Andrés Felipe Leal 1 , Eliana Benincore-Flórez 1, Daniela Solano-Galarza 1, Rafael Guillermo Garzón Jaramillo 1 , Olga Yaneth Echeverri-Peña 1, Diego A. Suarez 1,2, Carlos Javier Alméciga-Díaz 1,* and Angela Johana Espejo-Mojica 1,* 1 Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá 110231, Colombia; [email protected] (A.F.L.); [email protected] (E.B.-F.); [email protected] (D.S.-G.); [email protected] (R.G.G.J.); [email protected] (O.Y.E.-P.); [email protected] (D.A.S.) 2 Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 110231, Colombia * Correspondence: [email protected] (C.J.A.-D.); [email protected] (A.J.E.-M.); Tel.: +57-1-3208320 (ext. 4140) (C.J.A.-D.); +57-1-3208320 (ext. 4099) (A.J.E.-M.) Received: 6 July 2020; Accepted: 7 August 2020; Published: 27 August 2020 Abstract: GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. -
Clinicians Using the Classification Will Identify a Seizure As Focal Or Generalized Onset If There Is About an 80% Confidence Level About the Type of Onset
GENERALIZED ONSET SEIZURES Generalized onset seizures are not characterized by level of awareness, because awareness is almost always impaired. Generalized tonic-clonic: Immediate loss of Generalized epileptic spasms: Brief seizures with awareness, with stiffening of all limbs (tonic phase), flexion at the trunk and flexion or extension of the followed by sustained rhythmic jerking of limbs and limbs. Video-EEG recording may be required to face (clonic phase). Duration is typically 1 to 3 minutes. determine focal versus generalized onset. The seizure may produce a cry at the start, falling, tongue biting, and incontinence. Generalized typical absence: Sudden onset when activity stops with a brief pause and staring, Generalized clonic: Rhythmical sustained jerking of sometimes with eye fluttering and head nodding or limbs and/or head with no tonic stiffening phase. other automatic behaviors. If it lasts for more than These seizures most often occur in young children. several seconds, awareness and memory are impaired. Recovery is immediate. The EEG during these seizures Generalized tonic: Stiffening of all limbs, without always shows generalized spike-waves. clonic jerking. Generalized atypical absence: Like typical absence Generalized myoclonic: Irregular, unsustained jerking seizures, but may have slower onset and recovery and of limbs, face, eyes, or eyelids. The jerking of more pronounced changes in tone. Atypical absence generalized myoclonus may not always be left-right seizures can be difficult to distinguish from focal synchronous, but it occurs on both sides. impaired awareness seizures, but absence seizures usually recover more quickly and the EEG patterns are Generalized myoclonic-tonic-clonic: This seizure is like different. -
Ceramide and Related Molecules in Viral Infections
International Journal of Molecular Sciences Review Ceramide and Related Molecules in Viral Infections Nadine Beckmann * and Katrin Anne Becker Department of Molecular Biology, University of Duisburg-Essen, 45141 Essen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-201-723-1981 Abstract: Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit. Keywords: ceramide; acid sphingomyelinase; sphingolipids; lipid-rafts; α-galactosylceramide; viral Citation: Beckmann, N.; Becker, K.A. -
Report of the 2014 ELA Families / Scientists Meeting
Report 2014 ELA Families - Scientists meeting April 5 & 6, 2014 Paris, France 2014 ELA FAMILIES – SCIENTISTS MEETING April 5‐6, 2014 Paris, France The 2014 ELA Families/Scientists meeting gathered 360 participants in Paris, among them 27 international scientists with expertise in leukodystrophies and myelin diseases. During the 8 diseases’ workshops and the plenary session organized, scientists presented the results of their research work in lay language and answered questions from patients and their families. This special report compiles the information presented during the scientific workshops. Summary Diseases’ workshops . Workshop on ALD/AMN . Workshop on Refsum disease . Workshop on MLD . Workshop on Krabbe disease . Workshop on CACH/VWM syndrome, Alexander disease, MLC and Canavan disease . Workshop on PMD and other hypomyelinating leukodystrophies . Workshop on undetermined leukodystrophies . Workshop on Aicardi‐Goutières syndrome ‐‐‐ *ALD: AdrenoLeukoDystrophy; AMN: AdrenoMyeloNeuropathy; MLD: Metachromatic Leukodystrophy; CACH/VWM: Childhood Ataxia with Central nervous system Hypomyelination / Vanishing White Matter; MLC: Megalencephalic Leukoencephalopathy with subcortical Cysts; PMD: Pelizaeus‐Merzbacher Disease 2014 ELA Families/Scientists meeting ‐ Report Page 1 DISEASES’ WORKSHOPS WORKSHOP ON ALD/AMN CLINICAL TRIALS EVALUATING THE IMPORTANCE OF STRENGTH ON FUNCTION IN AMN Kathleen Zackowski Ph.D., OTR, MSCS Kennedy Krieger Institute, Baltimore, MD, USA X‐linked adrenoleukodystrophy, a progressive neurodegenerative disease, is caused by a defect in the ABCD1 gene. The disease has multiple subtypes, but the most common form is adrenomyeloneuropathy (AMN). Our previous studies identified the symptoms of the disease in men as slowly progressive spasticity, weakness and sensory dysfunction. The worsening of these symptoms results in the progressive difficulty of walking and of balance problems. -
Neuropathology Category Code List
Neuropathology Page 1 of 27 Neuropathology Major Category Code Headings Revised 10/2018 1 General neuroanatomy, pathology, and staining 65000 2 Developmental neuropathology, NOS 65400 3 Epilepsy 66230 4 Vascular disorders 66300 5 Trauma 66600 6 Infectious/inflammatory disease 66750 7 Demyelinating diseases 67200 8 Complications of systemic disorders 67300 9 Aging and neurodegenerative diseases 68000 10 Prion diseases 68400 11 Neoplasms 68500 12 Skeletal Muscle 69500 13 Peripheral Nerve 69800 14 Ophthalmic pathology 69910 Neuropathology Page 2 of 27 Neuropathology 1 General neuroanatomy, pathology, and staining 65000 A Neuroanatomy, NOS 65010 1 Neocortex 65011 2 White matter 65012 3 Entorhinal cortex/hippocampus 65013 4 Deep (basal) nuclei 65014 5 Brain stem 65015 6 Cerebellum 65016 7 Spinal cord 65017 8 Pituitary 65018 9 Pineal 65019 10 Tracts 65020 11 Vascular supply 65021 12 Notochord 65022 B Cell types 65030 1 Neurons 65031 2 Astrocytes 65032 3 Oligodendroglia 65033 4 Ependyma 65034 5 Microglia and mononuclear cells 65035 6 Choroid plexus 65036 7 Meninges 65037 8 Blood vessels 65038 C Cerebrospinal fluid 65045 D Pathologic responses in neurons and axons 65050 1 Axonal degeneration/spheroid/reaction 65051 2 Central chromatolysis 65052 3 Tract degeneration 65053 4 Swollen/ballooned neurons 65054 5 Trans-synaptic neuronal degeneration 65055 6 Olivary hypertrophy 65056 7 Acute ischemic (hypoxic) cell change 65057 8 Apoptosis 65058 9 Protein aggregation 65059 10 Protein degradation/ubiquitin pathway 65060 E Neuronal nuclear inclusions 65100 -
Myoclonic Status Epilepticus in Juvenile Myoclonic Epilepsy
Original article Epileptic Disord 2009; 11 (4): 309-14 Myoclonic status epilepticus in juvenile myoclonic epilepsy Julia Larch, Iris Unterberger, Gerhard Bauer, Johannes Reichsoellner, Giorgi Kuchukhidze, Eugen Trinka Department of Neurology, Medical University of Innsbruck, Austria Received April 9, 2009; Accepted November 18, 2009 ABSTRACT – Background. Myoclonic status epilepticus (MSE) is rarely found in juvenile myoclonic epilepsy (JME) and its clinical features are not well described. We aimed to analyze MSE incidence, precipitating factors and clini- cal course by studying patients with JME from a large outpatient epilepsy clinic. Methods. We retrospectively screened all patients with JME treated at the Department of Neurology, Medical University of Innsbruck, Austria between 1970 and 2007 for a history of MSE. We analyzed age, sex, age at seizure onset, seizure types, EEG, MRI/CT findings and response to antiepileptic drugs. Results. Seven patients (five women, two men; median age at time of MSE 31 years; range 17-73) with MSE out of a total of 247 patients with JME were identi- fied. The median follow-up time was seven years (range 0-35), the incidence was 3.2/1,000 patient years. Median duration of epilepsy before MSE was 26 years (range 10-58). We identified three subtypes: 1) MSE with myoclonic seizures only in two patients, 2) MSE with generalized tonic clonic seizures in three, and 3) generalized tonic clonic seizures with myoclonic absence status in two patients. All patients responded promptly to benzodiazepines. One patient had repeated episodes of MSE. Precipitating events were identified in all but one patient. Drug withdrawal was identified in four patients, one of whom had additional sleep deprivation and alcohol intake.