DOCSLIB.ORG

Lafora Disease in Miniature Wirehairs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lafora Disease in Miniature Wirehairs ACHSHUND Update DA NESTLÉ PURINA PUBLICATION DEDICATED TO DACHSHUND ENTHUSIASTS VOLUME 18 | SPRING 2020 LAFORA DISEASE IN MINIATURE WIREHAIRS Caution & Awareness Advised SPRING 2020 AWARENESS OF LAFORA DISEASE IN MINIATURE WIREHAIRED DACHSHUNDS COULD AID PREVENTION Miniature Wirehaired Dachshund was first recognized in Mini breeder Dianne Graham of Wirehairs in the U.K. more than Pulaski, Virginia, learned about three decades ago. Graham Lafora disease five years ago quickly realized that few U.S. when she discovered an English breeders knew about Lafora. dog in her dog’s pedigree was A late-onset progressive myo- affected. Two of her bitches clonic epilepsy seen in dogs tested as carriers of the auto- around 7 years of age, Lafora dis- somal recessive condition that ease at its peak in 2013 affected 2 DACHSHUND Update GENOTYPE RESULTS FOR LAFORA DISEASE (AUTOSOMAL RECESSIVE INHERITANCE) P/P Affected dogs have two copies of the mutant gene that causes the Positive/Positive condition and will develop the disease. P/N Carrier dogs have one copy of the normal gene and one copy of the Positive/Negative mutant gene. They will not develop the disease but will pass a mutant gene on to about half of their offspring. N/N Clear dogs have no copies of the mutant gene responsible for the Negative/Negative condition and will neither develop the condition nor pass it on to their offspring. up to 10 percent of Miniature FAMILY OF MINI WIRE- Wirehaired Dachshunds in the HAIRS SHARES LAFORA U.K. and 42 percent were carriers. A different scenario took Gradually, after a genetic test place in Miniature Wirehaired became available in 2012 to Dachshunds in the U.K., where owners and breeders, disease for decades before the gene incidence began to decrease. mutation for Lafora disease was In 2017, only 3 percent of Mini discovered, breeders had pro- “As far as I know, there Wirehairs in the U.K. were affected duced litters in which some dogs and 26 percent were deemed later in life showed signs of haven’t been any recent carriers. epilepsy. They suspected it was affected dogs with Lafora Graham made it her mission a hereditary condition, though to educate North American the late onset of clinical signs disease in the U.S.” breeders about the incurable meant that most dogs had already condition that eventually claims been bred when it became Dianne Graham, Miniature Wirehaired the lives of all affected dogs. She apparent they were affected. Dachshund breeder, Pulaski, Virginia began a database to record the In the 1990s, veterinary testing results of North American neurologists Clare Rusbridge, Miniature Wirehaired Dachshunds BVMS, PhD, DipECVN, FRCVS, and investigated the history of of the University of Surrey in affected dogs in America. Guildford, England, and Sue “As far as I know, there haven’t Fitzmaurice, BVSc, MRCVS, been any recent affected dogs DACVIM (Neurology), of The with Lafora disease in the U.S.,” Ralph Veterinary Referral Centre Graham says. “The only dog I am in Marlow, Buckinghamshire, aware of was brought to Canada England, found an extended in the late ‘80s as a 5-year-old family of Miniature Wirehairs in Champion. He started showing which the disease was clearly signs when he was 7 years old inherited. They sent pedigree and was put down when he was information and DNA from those in his teens. His frozen semen dogs to Berge A. Minassian, MD, was later tested, and he was of The Hospital for Sick Children found to be affected.” at the University of Toronto in 3 SPRING 2020 Canada, who was studying a their cells into large accumula- similar inherited, severe form of tions called Lafora bodies. The progressive myoclonic epilepsy gene mutation disables the gene in humans that occurs in late from controlling laforin and from childhood or adolescence. protecting tissue against carbo- Dr. Minassian identified the hydrate accumulation. As the Epm2b gene mutation for Lafora Lafora bodies gradually grow, disease in the Mini Wirehairs they have a neurotoxic effect in 2005 and matched it to the in the central nervous system. human Lafora disease mutations When Lafora bodies amass in the EPM2A gene and the within the nerve cells of the brain, EPM2B gene. Affected dogs, the cells start to malfunction as well as affected people, and degenerate causing neural inherit two copies of the gene problems such as twitching, mutation. The Epm2b gene jerking and sometimes seizures. mutation in dogs results in the As the disease progresses, the intracellular accumulation of dogs experience other neuro- abnormal glycogen phospha- logical problems, including tase laforin, a protein essential dementia and difficulty walking. for making normal structured Besides brain tissue, Lafora glycogen. bodies are found in muscles, Affected dogs are not able skin, liver, and heart. Although to convert starch into sugar, so Lafora disease appears as pro- insoluble glycogen builds up in gressive myoclonic epilepsy, it is actually a glycogen metabo- SIGNS OF LAFORA DISEASE lism disorder. Besides Miniature Wirehaired Among the initial signs of Lafora disease in Miniature Wirehaired Dachshunds, the disease is Dachshunds, owners participating in a breed health survey found in Basset Hounds and reported the following. The average age of onset for the dogs Beagles, with all three breeds in the survey was 6.94 years, with most dogs living a few years sharing the same single muta- after diagnosis. tion that leads to near-absent • Myoclonus, or sudden twitches or jerks, of the neck and limbs expression and loss of function was the most common sign, affecting 78 percent of dogs. of the gene. The canine mutation Myoclonus may be spontaneous or a reflex action triggered consists of a variable expansion by sudden noise, bright light, sudden movement, or flickering of a dodecamer repeat sequence visual stimuli. in the Epm2b gene. • Hypnic jerks, the type of sudden jerks people experience as Originally, gene sequencing they fall asleep, was the second most common sign, occurring options were limited, as the in 52 percent of dogs. traditional method of polymerase • Generalized tonic-clonic seizures were the third most common chain reaction (PCR)-based sign, affecting 41 percent of dogs. sequencing was unreliable for • Less common signs included focal seizures characterized by detecting carriers. At The Hospital “jaw smacking,” “fly catching” or panic attacks. for Sick Children, Dr. Minassian • Later signs include dementia, blindness, aggression to people and his team used a Southern and dogs, deafness, and fecal and urinary incontinence due blot test to identify the mutation to loss of housetraining. and to provide DNA screening of dogs using blood samples. 4 DACHSHUND Update U.K. DACHSHUND more than 40,000 pounds LOVERS JOIN FORCES ($52,000) toward the develop- “If we are concerned with The gene mutation discovery ment of a DNA test and for a for Lafora disease united mem- subsidy program to enable breed- breeding healthy dogs, we bers of the Wirehaired Dachs- ers to screen their dogs. After hund Club of the U.K. to work the test became available at The should be aware of Lafora together to educate breeders Hospital for Sick Children in 2012, and the opportunity to test about the estimation of breeding breeders could take advantage probability of the recessive condi- of the subsidized testing program our dogs to ensure the tion. The goal was to eradicate if they agreed not to breed the disease from the breed. carrier or affected dogs. disease does not affect Efforts to develop a commer- Further, the Wirehaired Dachs- dogs here.” cial test for the gene mutation hund Club asked The Kennel Club to require DNA testing for Lafora would not be easy since PCR Kenneth Levison, treasurer, disease for Miniature Wirehairs sequencing — the more common Dachshund Club of America and affordable type of genetic bred by the club’s Assured testing — was not possible to Breeders, a designation for identify carriers. The Southern breeders who adhere to good blot method required a blood breeding practices for their breed. sample, took months to process Results for every dog tested and cost around $300. would be published on The With help from the Dachshund Kennel Club’s health test website. Breed Council and The Kennel “The DNA test is now an official Club Charitable Trust, the Wire- requirement under The Kennel haired Dachshund Club raised Club’s Assured Breeder program, 5 SPRING 2020 and no responsible breeder in ture Wirehairs in the U.K. were the U.K. would breed Miniature affected with Lafora, possibly Wirehairs without knowing the as many as 500 dogs, with 50 to Lafora status of the parents,” 100 affected dogs born a year, says Ian Seath, chair of the Seath says. “The proportion Dachshund Breed Council. of litters that could potentially To convince breeders who produce an affected puppy were not part of the Assured was estimated to be about Breeders program, Seath and 55 percent,” he says. other members of the Dachs- After the Wirehaired Dachs- hund Breed Council presented hund Club began holding Lafora data on the disease. “It was a screening sessions two times a much more powerful message year, with 50 to 60 dogs screened to state the number of Mini per session, the number began Wirehair puppies born over to decrease. Between 2012 and a particular time period and 2017, more than 700 Miniature the percent that we expect to Wirehairs were DNA tested for be affected by Lafora disease Lafora. With a goal of zero dogs because they were bred from affected, the Wirehaired Dachs- untested parents,” Seath says. hund Club of England continues In 2010, it was estimated that to monitor test results and from 5 to 10 percent of Minia- post them online quarterly.
Load more

Recommended publications
  • Lafora Disease: Molecular Etiology Lafora Hastalığı: Moleküler Etiyoloji S
    Epilepsi 2018;24(1):1-7 DOI: 10.14744/epilepsi.2017.48278 REVIEW / DERLEME Lafora Disease: Molecular Etiology Lafora Hastalığı: Moleküler Etiyoloji S. Hande ÇAĞLAYAN1,2 1Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey S. Hande CAĞLAYAN, Ph.D. 2International Biomedicine and Genome Center, Dokuz Eylül University, İzmir, Turkey Summary Lafora Disease (LD) is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies (LBs). Patients with LD manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurological deteri- oration beginning at the age of 8-18 years. Mutations in either EPM2A gene encoding protein phosphatase laforin or NHLRC1 gene encoding ubiquitin-ligase malin cause LD. Approximately, 200 distinct mutations accounting for the disease are listed in the Lafora progressive my- oclonus epilepsy mutation and polymorphism database. In this review, the genotype-phenotype correlations, the genetic diagnosis of LD, the downregulation of glycogen metabolism as the main cause of LD pathogenesis and the regulation of glycogen synthesis as a key target for the treatment of LD are discussed. Key words: EPM2A and NHLRC1 gene mutations; genotype-phenotype relationship; Lafora progressive myoclonus epilepsy; LD pathogenesis. Özet Lafora hastalığı (LD) Lafora cisimleri (LB) olarak bilinen anormal glikojen yapıların birikmesi ile karakterize olan ölümcül bir nörodejeneratif hastalıktır. Lafora hastalarında 8–18 yaş arası başlayan miyoklonik ve tonik-klonik nöbetler, halüsinasyonlar ve ilerleyen nörolojik bozulma görülür. Lafora hastalığı protein fosfataz laforini kodlayan EPM2A geni veya ubikitin ligaz malini kodlayan NHLRC1 geni mutasyonları ile orta- ya çıkar. Hastalığa sebep olan yaklaşık 200 farklı mutasyon “Lafora Progressive Myoclonus Epilepsy Mutation and Polymorphism Database” de listelenmiştir.
    [Show full text]
  • ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper by the ILAE Task Force on Nosology and Definitions
    ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper by the ILAE Task Force on Nosology and Definitions N Specchio1, EC Wirrell2*, IE Scheffer3, R Nabbout4, K Riney5, P Samia6, SM Zuberi7, JM Wilmshurst8, E Yozawitz9, R Pressler10, E Hirsch11, S Wiebe12, JH Cross13, P Tinuper14, S Auvin15 1. Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu’ Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, Rome, Italy 2. Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester MN, USA. 3. University of Melbourne, Austin Health and Royal Children’s Hospital, Florey Institute, Murdoch Children’s Research Institute, Melbourne, Australia. 4. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker–Enfants Malades Hospital, APHP, Member of European Reference Network EpiCARE, Institut Imagine, INSERM, UMR 1163, Université de Paris, Paris, France. 5. Neurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia. Faculty of Medicine, University of Queensland, Queensland, Australia. 6. Department of Paediatrics and Child Health, Aga Khan University, East Africa. 7. Paediatric Neurosciences Research Group, Royal Hospital for Children & Institute of Health & Wellbeing, University of Glasgow, Member of European Refence Network EpiCARE, Glasgow, UK. 8. Department of Paediatric Neurology, Red Cross War Memorial Children’s Hospital, Neuroscience Institute, University of Cape Town, South Africa. 9. Isabelle Rapin Division of Child Neurology of the Saul R Korey Department of Neurology, Montefiore Medical Center, Bronx, NY USA. 10. Programme of Developmental Neurosciences, UCL NIHR BRC Great Ormond Street Institute of Child Health, Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children, London, UK 11.
    [Show full text]
  • Mutations in the NHLRC1 Gene Are the Common Cause for Lafora Disease in the Japanese Population
    J Hum Genet (2005) 50:347–352 DOI 10.1007/s10038-005-0263-7 ORIGINAL ARTICLE Shweta Singh Æ Toshimitsu Suzuki Æ Akira Uchiyama Satoko Kumada Æ Nobuko Moriyama Æ Shinichi Hirose Yukitoshi Takahashi Æ Hideo Sugie Æ Koichi Mizoguchi Yushi Inoue Æ Kazue Kimura Æ Yukio Sawaishi Kazuhiro Yamakawa Æ Subramaniam Ganesh Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population Received: 11 March 2005 / Accepted: 30 May 2005 / Published online: 15 July 2005 Ó The Japan Society of Human Genetics and Springer-Verlag 2005 Abstract Lafora disease (LD) is a rare autosomal NHLRC1 and encoding a putative E3 ubiquitin ligase, recessive genetic disorder characterized by epilepsy, was recently identified on chromosome 6p22. The LD is myoclonus, and progressive neurological deterioration. relatively common in southern Europe, the Middle East, LD is caused by mutations in the EMP2A gene encoding and Southeast Asia. A few sporadic cases with typical a protein phosphatase. A second gene for LD, termed LD phenotype have been reported from Japan; however, our earlier study failed to find EPM2A mutations in four Japanese families with LD. We recruited four new fam- S. Singh Æ S. Ganesh Department of Biological Sciences and Bioengineering, ilies from Japan and searched for mutations in EPM2A. Indian Institute of Technology, All eight families were also screened for NHLRC1 Kanpur, India mutations. We found five independent families having T. Suzuki Æ K. Yamakawa (&) novel mutations in NHLRC1. Identified mutations in- Laboratory for Neurogenetics, clude five missense mutations (p.I153M, p.C160R, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, p.W219R, p.D245N, and p.R253K) and a deletion Saitama 351-0198, Japan mutation (c.897insA; p.S299fs13).
    [Show full text]
  • Lafora Disease Masquerading As Hepatic Dysfunction
    Thomas Jefferson University Jefferson Digital Commons Abington Jefferson Health Papers Abington Jefferson Health 8-24-2018 Lafora Disease Masquerading as Hepatic Dysfunction Faisal Inayat Allama Iqbal Medical College Waqas Ullah Abington Jefferson Health Hanan T. Lodhi University of Nebraska at Omaha Zarak H. Khan St. Mary Mercy Hospital Livonia Ghulam Ilyas SUNY Downstate Medical Center Follow this and additional works at: https://jdc.jefferson.edu/abingtonfp See next page for additional authors Part of the Gastroenterology Commons, and the Medical Genetics Commons Let us know how access to this document benefits ouy Recommended Citation Inayat, Faisal; Ullah, Waqas; Lodhi, Hanan T.; Khan, Zarak H.; Ilyas, Ghulam; Ali, Nouman Safdar; and Abdullah, Hafez Mohammad A., "Lafora Disease Masquerading as Hepatic Dysfunction" (2018). Abington Jefferson Health Papers. Paper 7. https://jdc.jefferson.edu/abingtonfp/7 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Abington Jefferson Health Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Authors Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, and Hafez Mohammad A.
    [Show full text]
  • Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
    1 Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities Fiona M Menzies1ǂ,#, Angeleen Fleming1ǂ, Andrea Caricasole2ǂ, Carla F Bento1ǂ, Steven P Andrews2ǂ, Avraham Ashkenazi1ǂ, Jens Füllgrabe1ǂ, Anne Jackson1ǂ, Maria Jimenez Sanchez1ǂ, Cansu Karabiyik1ǂ, Floriana Licitra1ǂ, Ana Lopez Ramirez1ǂ, Mariana Pavel1ǂ, Claudia Puri1ǂ, Maurizio Renna1ǂ, Thomas Ricketts1ǂ Lars Schlotawa1ǂ, Mariella Vicinanza1ǂ, Hyeran Won1ǂ, Ye Zhu1ǂ, John Skidmore2ǂ and David C Rubinsztein1* 1 Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK. 2 Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0AH, UK. # Current address: Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road Windlesham, Surrey, GU20 6PH, UK. ǂDenotes equal contribution *E-mail address for correspondence: [email protected] (DCR) 2 In Brief This review discusses the importance of autophagy function for brain health, outlining connections between autophagy dysfunction and neurodegenerative disorders. The potential for autophagy as a therapeutic strategy for neurodegenerative disease is discussed, along with how this may be achieved. Summary Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knock-out studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation, as well as other roles including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases.
    [Show full text]
  • Types of Photic-Induced Seizures and Epileptic Types Associated With
    SEIZURE DISORDERS EPILEPTIC SYNDROMES AND PHOTOSENSITIVE SEIZURES The clinical features of different types of photic-induced seizures and epileptic syndromes characterized by visual sensitivity are reviewed from the University of Pisa, Italy, and Centre St Paul, Marseille, France. Seizure types associated with clinical photosensitivity include eyelid myoclonus, generalized myoclonic jerks, tonic-versive seizures, absence, generalized tonic clonic, and focal seizures. Epileptic syndromes with photic-induced seizures include benign myoclonic epilepsy in infancy, absence epilepsy, juvenile myoclonic epilepsy, epilepsy with myoclonic-astatic seizures, primary reading epilepsy, severe myoclonic epilepsy of infancy, photosensitive occipital lobe epilepsy, and progressive myoclonus epilepsies (PME). PME with photic sensitivity are symptoms of neuronal ceroid lipofuscinosis, Lafora's disease, Unverricht-Lundborg disease, and myoclonus epilepsy and ragged red fibers (MERRF). Visually induced seizures can be generalized or focal, idiopathic or symptomatic, or represent a pure reflex photosensitive epilepsy. (Guerrini R, Genton P. Epileptic syndromes and visually induced seizures. Epilepsia January 2004;45 (Suppl 1): 14- 18). (Reprints: Dr R Guerrini, Division of Child Neurology and Psychiatry, University of Pisa & IRCCS Fondazione Stella Maris, via dei Giacinti 2, 56018 Calambrone, Pisa, Italy). COMMENT. The treatment of photosensitive epilepsies involves preventive measures and antiepileptic medications (AED). (Covanis A et al. Epilepsia Jan 2004;45(Suppl l):40-45; Bureau M et al. Epilepsia Jan 2004;45(Suppl l):24-26). Preventive measures include the following: avoid stimuli (eg TV, videogames); use small TV, 100-Hz screen, remote control, sit >2 m away from screen, wear spectacles, avoid stress and fatigue. Usually a combination of avoidance of stimuli and an AED is necessary.
    [Show full text]
  • Relation of Photosensitivity to Epileptic Syndromes
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.49.12.1386 on 1 December 1986. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1386-1391 Relation of photosensitivity to epileptic syndromes P WOLF,* R GOOSSES Abteilungfiir Neurologie, Klinikum Charlottenburg der Freien Universitdt, Berlin, Federal Republic ofGermany SUMMARY Photosensitivity is the most common mode of seizure precipitation. It is age-related, more frequent in females, and most often found in generalised epilepsies. Little is known about its relation to individual epileptic syndromes. This study on 1062 epileptic patients who had 4007 split screen video EEG investigations revealed that the relation to generalised epilepsy is even more close than generally believed. Versive seizures with visual hallucinations was the only focal seizure type related to photosensitivity. Of the syndromes of generalised epilepsy, only childhood absence epi- lepsy, juvenile myoclonic epilepsy, and epilepsy with grand mal on awakening were related to photosensitivity. The closest correlation was with juvenile myoclonic epilepsy. This is confirmed by a relation to the poly-spike wave pattern, and by an increase of myoclonic seizures by intermittent light stimuli. No relation was found with early childhood syndromes of generalised epilepsy, or generalised tonic-clonic seizures in the evening, or, most remarkably, with juvenile absence epilepsy. guest. Protected by copyright. In generalised epilepsies with onset around puberty, photosensitivity could thus act as a patho- plastic factor. The female preponderance in both childhood absences and photosensitivity could be due to the same unknown factor. Photosensitivity does not necessarily signify epi- of increasing and decreasing frequency from 3 to 30 Hz were lepsy.' In connection with epilepsy, photosensitivity applied.
    [Show full text]
  • A Type of Progressive Myoclonic Epilepsy, Lafora Disease: a Case Report
    Eastern Journal of Medicine 18 (2013) 34-36 Case Report A type of progressive myoclonic epilepsy, Lafora disease: A case report Ömer Bektaşa,*, Arzu Yılmaza, Aylin Heper Okcuc, Serap Teberb, Erhan Aksoya, Gülhis Dedaa aDepartment of Pediatric Neurology, School of Medicine, Ankara University,Turkey bDepartment of Pediatric Neurology, Dıskapı Hematology-Oncology Hospital, Turkey cDepartment of Pediatric Pathology, School of Medicine, Ankara University, Turkey Abstract. Lafora disease is a rare group of progressive myoclonic epilepsies characterized with progressive neurological dysfunction, myoclonus, focal and generalized seizures. Generally, a generalized tonic clonic seizure is the first symptom of the disease. An 11-year-old male patient had been followed-up at another center for epilepsy for 8 years. The patient had a history of myoclonic seizures for nearly every day for the last 2 years and cognitive detoriation for the last 8 months. He admitted to our hospital with the desire of his family. Eccrine sweat gland biopsy was performed. The biopsy of the sweat gland was positive for PAS and contained diastase resistant polyglican content (Lafora bodies), and thus, a diagnosis of Lafora disease was established. The patient presented here constitutes a rare case of pediatric epilepsy, which caused neurodegeneration in late-childhood and onset with typical epilepsy symptoms. This report also aimed to show that biopsy obtained from proper area is important for diagnosis Our patient developed cognitive dysfunction a short period of eight months. To our knowledge, this is the shortest period in literature. Key words: Lafora Disease, progressive myoclonic epilepsy, neurodegeneration 1. Introduction 2. Case report Progressive myoclonic epilepsy is a rare group An 11-year-old male patient had been followed- of diseases characterized with progressive up for epilepsy for 8 years.
    [Show full text]
  • Lafora Disease and Congenital Generalized Lipodystrophy: a Case Report
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector LAFORA DISEASE AND CONGENITAL GENERALIZED LIPODYSTROPHY: A CASE REPORT Chih-Fan Tseng,1 Che-Sheng Ho,1,2 Nan-Chang Chiu,1,2 Shuan-Pei Lin,1,2,3 Chi-Yuan Tzen,2,4 and Yu-Hung Wu2,5 Departments of 1Pediatrics, 3Medical Research, 4Pathology and 5Dermatology, Mackay Memorial Hospital; and 2Mackay Medicine, Nursing and Management College, Taipei, Taiwan. We report a patient with congenital generalized lipodystrophy who had suffered from seizures, myoclonus, ataxia and cognitive decline since late childhood. Lafora disease was diagnosed based on skin biopsy results, which revealed pathognomonic Lafora bodies. The results of genetic analysis for mutations in EPM2A and EPM2B genes were negative. This is the first case report describing an association between congenital generalized lipodystrophy and Lafora dis- ease. Further studies focusing on the relationship between these two diseases and the identifica- tion of a third locus for Lafora disease are needed. Key Words: Lafora disease, lipodystrophy, myoclonus, progressive myoclonic epilepsy (Kaohsiung J Med Sci 2009;25:663–8) Congenital generalized lipodystrophy (Berardinelli- develop during late childhood or adolescence. We Seip syndrome) was initially reported by Berardinelli report a child with congenital generalized lipodys- [1] and Seip [2] and is an extremely rare autosomal trophy and LD, a previously undescribed association, recessive disorder with genetic heterogeneity. Its and attempt to clarify the relationship between these prevalence has been estimated to be less than one in two diseases. one million. Three different loci (AGPAT2, BSCL2 and CAV1), which map to chromosomes 9q34, 11q13 and 7q31, respectively, have been identified [3–5].
    [Show full text]
  • A Novel Deletion Mutation in EPM2A Underlies Progressive Myoclonic Epilepsy (Lafora Body Disease) in a Pakistani Family
    Neurology Asia 2021; 26(2) : 427 – 433 A novel deletion mutation in EPM2A underlies progressive myoclonic epilepsy (Lafora body disease) in a Pakistani family 1Fizza Orooj MRCP, 2Umm-e-Kalsoom PhD, 3XiaoChu Zhao, 1Arsalan Ahmad MD, 4Imran Nazir Ahmed MD, 5Muhammad Faheem PhD, 5Muhammad Jawad Hassan PhD, 3,6Berge A. Minasian MD 1Division of Neurology, Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad, Pakistan; 2Department of Biochemistry, Hazara University, Mansehra, KPK, Pakistan; 3Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada; 4Department of Pathology, Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad, Pakistan; 5Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan; 6Department of Pediatrics, University of Texas Southwestern, Dallas, Teas, USA Abstract Lafora body disease (MIM-254780), a glycogen storage disease, characterized by Lafora bodies (deformed glycogen molecules) accumulating in multiple organs, is a rare form of myoclonic epilepsy. It manifests in early adolescent years, initially with seizures and myoclonus, followed by dementia and progressive cognitive decline, ultimately culminating in death within 10 years. In Pakistan so far 5 cases have been reported. Here, we report a new case of Lafora body disease belonging to a consanguineous family from Pakistan. Histopathological analysis confirmed presence of lafora bodies in the patient`s skin. Sanger sequencing revealed novel homozygous 5bp deletion mutation (NM_005670.4; c.359_363delGTGTG) in exon 2 of the EPM2A gene, which was truly segregated in the family. These results will increase our understanding regarding the aetiology of this disorder and will further add to the mutation spectrum of EPM2A gene.
    [Show full text]
  • The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force
    The Cerebellum (2019) 18:1098–1125 https://doi.org/10.1007/s12311-019-01052-2 CONSENSUS PAPER The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force Marie Beaudin1,2 & Antoni Matilla-Dueñas3 & Bing-Weng Soong4,5 & Jose Luiz Pedroso6 & Orlando G. Barsottini6 & Hiroshi Mitoma7 & Shoji Tsuji8,9 & Jeremy D. Schmahmann10 & Mario Manto11,12 & Guy A Rouleau13 & Christopher Klein14 & Nicolas Dupre1,2 Published online:: 2 J uly 2019 # The Author(s) 2019 Abstract There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus on the classification of autosomal recessive ataxias in order to develop a general approach to a patient presenting with ataxia, organize disorders according to clinical presentation, and define this field of research by identifying common pathogenic molecular mechanisms in these disorders. The work of this task force was based on a previously published systematic scoping review of the literature that identified autosomal recessive disorders characterized primarily by cerebellar motor dysfunction and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. We identified 59 disorders that are classified as primary autosomal recessive cerebellar ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. These primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia.
    [Show full text]
  • An Unprecedented Impact a Series of Fact Sheets on Covid-19 and Biomedical Research July 2020
    AN UNPRECEDENTED IMPACT A SERIES OF FACT SHEETS ON COVID-19 AND BIOMEDICAL RESEARCH JULY 2020 We must maintain and strengthen our nation’s investment in medical research through the National Institutes of Health. This is an urgent priority for Congress, as our nation works to restart stalled research, keep up with pressing public health challenges, continue to fightCOVID-19 and prepare for the next potential pandemic. PART 3 | PROGRESS ON HOLD | Researcher Profiles While research on the disease caused by the novel coronavirus has been on a fast track the past several months, most other medical research ground to a halt in March and has yet to resume at anything near its pre-COVID pace. It is impossible to know the full implications of suspended work, lost experiments and delayed clinical trials, but for those waiting for a cure, time matters. After 17 years of work, DR. MATTHEW GENTRY is within reach of the holy grail — a potential treatment for Lafora disease, a devastating and The episodes increase quickly, and extremely rare form of epilepsy that strikes healthy regression is pretty fast. As we still teens and takes their lives within 10 years. In March, don’t know the window of opportunity his lab was preparing to conduct one final mouse test, a crucial step toward the goal of testing treatments in to treat and find a response, every patients by next year. That’s when COVID hit and the month matters to these patients. University of Kentucky was forced to shut down all non-essential activity — including his.
    [Show full text]