Lafora disease is an inherited form of epilepsy that affects miniature wirehaired dachshunds. Pdf lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. Skin biopsies of three patients with lafora disease clinically typical and proven by liver biopsy showed paspositive inclusions in numerous peripheral cells of eccrine sweat ducts. We report an electroencephalographic study in four cases of histologically proven lafora body disease. If you have problems viewing pdf files, download the latest version of adobe reader. Genotypes and phenotypes of patients with lafora disease living in. A recurrent homozygous nhlrc1 variant in siblings with lafora. The condition is characterised by a late onset of epilepsy, myoclonus and dementia. Many of these mutations change single protein building blocks amino acids in the laforin protein. The disease usually manifests in previously healthy. The disease is due to a mutation in the epm2b gene which results in intracellular accumulation of abnormal glycogen lafora bodies.
Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. The cure for all diseases with many case histories of diabetes, high blood pressure, seizures, chronic fatigue syndrome, migraines, alzheimers, parkinsons, multiple sclerosis, and others showing that all of these can be simply investigated and cured. Saltiel 1,3 1 department of internal medicine and department of physiology, life scien ces institute, university of michigan medical center, ann arbor, michigan 48109, usa. This is the first case report describing an association between congenital generalized lipodystrophy and lafora disease. As the disease progresses, the dogs experience other neurological problems, including dementia and difficulty walking. Lafora is a progressive and eventually fatal form of epilepsy. Almost all mutations in this gene prevent cells from producing any laforin or lead.
Lafora bodies are known to be neurotoxic, and therefore gliosis is widely observed in the lafora disease mouse models 10,11,24. To check if the reduction in the lafora bodies is associated with reduced gliosis as well in the double mutant, we looked at the distribution of glial fibrillary acidic protein gfap, an established marker of gliosis. Lafora disease neurology michigan medicine confluence. Lafora disease and congenital generalized lipodystrophy. Fulltext pdf blink reflex in progressive myoclonic epilepsies. Lafora disease was diagnosed based on skin biopsy results, which revealed pathognomonic lafora bodies. Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism disorder. Before you combine the files into one pdf file, use merge pdf to draganddrop pages to reorder or to delete them as you like. Number 1 january 2020 prevalence and incidence of rare diseases. Quick guide to cdbg eligible activities to support infectious disease response march 19, 2020 grantees should coordinate with local health authorities before undertaking any activity to support state or local pandemic response. When you hear, read, or watch news about an outbreak of an infectious disease such as ebola, you may feel anxious and show signs of stresseven when the outbreak affects people far from where you live and you are at low or no risk of getting sick. Lafora disease is the principal form of adolescenceonset progressive myoclonus epilepsy.
Lafora disease in a malaysian with a rare mutation in the epm2a gene. Case study by mental health aspects of developmental disabilities. Issn lafora disease ld is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus andor generalized seizures, visual hallucinations. Lafora disease is a fatal autosomal recessive, genetic disorder characterized by the presence of inclusion bodies, known as lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin. Lafora disease genetic and rare diseases information center. Medical and mental health complications of lafora disease. Besides brain tissue, lafora bodies are found in muscles, skin, liver, and heart. Earliest symptoms are headaches, decline in school performance, spontaneous and induced myoclonus, and. The kennel club charitable trust registered charity no.
Lafora disease affects a small number of people compared to the general population and is considered rare in many parts of the world. Unusual course of lafora disease university of groningen. Lafora disease, is a rare, adultonset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually res. Lafora progressive myoclonus epilepsy lafora disease is a rare. Suppression of leptin signaling reduces polyglucosan. Research open access loss of gabaergic cortical neurons. Canine epilepsy and lafora disease elsa beltran dvm, mrcvs, dipecvn.
Canine epilepsy and lafora disease the dachshund breed. Over time, insoluble starch platelets gradually build up in the central nervous system. Lafora disease is an inherited, severe form of progressive myoclonus epilepsy. Lafora disease in miniature wirehaired dachshunds plos. The average age of onset for the dogs in the survey was 6. Lafora disease is an inherited, severe form of progressive myoclonus. The documents contained in this web site are presented for information purposes only.
This website is intended for pathologists and laboratory personnel, who understand that medical information is imperfect and must be interpreted using reasonable medical judgment. What lafora disease is it is a progressive neurologic disease characterized by seizures, mioclonia, brain symptoms and psychic deterioration. Lafora s disease is a neurometabolic disease characterized by progressive myoclonus epilepsy. Defects in glycogen metabolism underlie the glycogen storage diseases gsds, genetic disorders with variable clinical phenotypes depending on the mutation type and affected genes. Elsa beltran dvm mrcvs made a presentation on lafora disease to the beagle clubs health seminar in february 2011. Quick guide to cdbg eligible activities to support. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for lafora disease. Dachshund health information library dachshund health uk.
Earliest symptoms are headaches, decline in school performance, spontaneous and induced myoclonus, and convulsive seizures, with eeg showing background slowing. Lafora disease ld is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature wirehaired dachshund. Pdf lafora disease from pathogenesis to treatment strategies. Twentyone cases 12 males, 9 females of lafora s disease in 16 families were studied at the national institute of mental health and neuro sciences nimhans, bangalore, india. Export to pdf export to word view visio file copy pages. Pdf lafora disease ld is an autosomal recessive progressive myoclonus epilepsy due to mutations in the epm2a laforin and epm2b malin genes, with. Death within four to ten years has been the inevitable outcome in all reported cases. The disease is hallmarked not only by seizures, of which jess has all types tc, myoclonic, absence, atonic, complex partial, but also intellectual decline, dementia, trouble speaking, walking and generally doing anything fullfunctioning teens can do. Lafora body disease is a rare neurometabolic disorder of autosomal recessive inheritance. Lafora disease is a fatal autosomal recessive, genetic disorder characterized by the presence of inclusion bodies, known as lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin 545 lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism. Signs of lafora disease among the initial signs of lafora disease in miniature wirehaired dachshunds, owners participating in a breed health survey reported the following. The diagnosis of lafora s disease is based on both clinical symptomatology and histologic detection of intracytoplasmic periodic acidschiffpositive inclusions, termed lafora bodies. This is the first reported case in which the diagnosis has been made by axillary skin biopsy in a patient with myoclonus but no other neurological symptoms.
Diagnosis by axilla skin biopsy in an early case of lafora. Psychology and mental health dementia case studies causes of disabled persons myoclonic epilepsy care and treatment development and progression diagnosis. No therapeutics or interventions exist for this devastating disease. All uploads and downloads are deemed secure and files are permanently deleted from the smallpdf servers within an hour. Described for the first time in 1911 by gonzalo rodriguez lafora 18861971 a spanish neurologist. The results of genetic analysis for mutations in epm2a and epm2b genes were negative.
Coping with stress during infectious disease outbreaks. Lafora disease ld is an autosomal recessive progressive myoclonus epilepsy due to mutations in the epm2a laforin and epm2b malin genes, with no. Lafora disease ld is a fatal autosomal recessive form of progressive myoclonus epilepsy. Lafora disease ld is a rare, inherited, severe, progressive myoclonic. Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures epilepsy and a decline in intellectual function. Pdf lafora disease ld is an autosomal recessive progressive myoclonus epilepsy due to mutations in the epm2a laforin and epm2b. More than 50 mutations in the epm2a gene have been identified in people with lafora progressive myoclonus epilepsy.
Lafora progressive myoclonus epilepsy genetics home. Lafora disease in dogs lafora disease is a hereditary disorder and is known to be transmitted as an autosomal recessive pattern. Lafora disease ld is a fatal form of progressive myoclonus epilepsy and a nonclassical gsd. By electronmicroscopy, the inclusions consisted of polyglucosantype material. Research open access loss of gabaergic cortical neurons underlies the neuropathology of lafora disease saida ortolano1, irene vieitez1, roberto carlos agisbalboa2 and carlos spuch2 abstract background. Lafora disease genetic and rare diseases information. Lafora disease lafora disease ld is an adolescenceonset, genetic, and fatal form of neurodegenerative disorder with diseasedefining symptoms such as progressive myoclonus epilepsy, ataxia, muscle wasting, and intellectual disabilities. Bibliographic data prevalence, incidence or number of published cases listed by diseases in alphabetical order. Other signs and symptoms include difficulty walking, muscle spasms myoclonus and dementia. Lafora disease is an autosomal recessive form of progressive myoclonic epilepsy caused by defects in. Breed health plans, report on your dachshunds health, breed health survey data.
Lafora progressive myoclonus epilepsy genetics home reference. It is thought to be transmitted by autosomal recessive inheritance. Myoclonus, seizures and progressive dementia are the main clinical features in lafora s disease. Later in the course, this disease mirrors unverrichtlundborg disease lafora bodies are not present on autopsy in this disease, and the mutation is in the cystatin b gene which causes defective functioning of a cysteine protease inhibitor. The following links will open a pdf file in a new browser window. The definitive place to find health and welfare information on dachshunds in the uk. Most patients are completely normal in childhood, with the exception of early learning difficulties in some ganesh et al. Affected people also experience rapid cognitive deterioration that begins around the same time as the seizures. Symptoms develop because the dog cannot efficiently process starch into sugar. This case study describes in detail a case of lafora disease, from its earliest stages through the clinical progression, including detailed neurophysiological studies, diagnostic biopsy and autopsy. Mutations in two genes, epm2a laforin and epm2b malin are causative of more than 90 percent of ld.
The pathognomonic sign of ld is the presence of abnormal glycogen which precipitates and accumulates into starchlike masses called lafora bodies lb. Lafora disease ld is a devastating childhood epilepsy caused by intracellular, aberrant glycogen aggregates called lafora bodies lbs in the brain and other tissues. The condition most commonly begins with epileptic seizures in late childhood or adolescence. The health and welfare website of the uk dachshund breed council. Grantees may use community development block grant cdbg funds for a range of eligible activities that. Lafora disease myoclonic epilepsy omim 254780 is a familial, degenerative disorder with the clinical triad of seizures, myoclonus, and dementia. Although these pathogenic variants may be associated with a variable phenotype, including both severe and mild clinical course, the clinical presentation of our patient at this age is very unusual for lafora disease. Adult polyglucosan body disease is a chronically progressive. Progressive myoclonus epilepsy with lafora inclusion bodies. Identification and characterization of genes in the lafora. Targeting pathogenic lafora bodies in lafora disease using. Other mutations delete or insert genetic material in the epm2a gene. Lafora disease, is a fatal autosomal recessive genetic disorder characterized by the presence of inclusion bodies, known as lafora bodies, within neurons and the cells of the heart, liver, muscle, and skin.
Structural biochemistrylafora disease wikibooks, open. If you would like to save the pdf file to your computer, follow these steps. Although lafora disease appears as progressive myoclonic epilepsy, it is actually a glycogen metabolism disorder. A role for agl ubiquitination in the glycogen storage. A case report abstract lafora disease is a type of progressive myoclonic epilepsy with poor prognosis, characterized by myoclonus, seizures, cerebellar ataxia and mental disorder.
Typical progression of myoclonic epilepsy of the lafora. Laforin, encoded by the epm2a gene, is a phosphatase, with a carbohydatebinding domain, which is mutated in patients with lafora disease. Senior clinician in neurology neurosurgery the animal health trust, lanwades park, kenford, newmarket introduction epileptic seizures are one of the most common chronic neurological diseases in the canine species. Symptoms begin in the second decade with progressive myoclonic epilepsy and survival is unusual beyond the age of 30. Unfortunately, the field of rare diseases as a whole suffers from a shortage of medical and scientific knowledge, largely due to lack of awareness and funding sources. In internet explorer, rightclick on the link and select save target as. Aht presentation on lafora disease dachshund health uk. Lafora s aforas disease is a rare form of myoclonus epilepsy. Patients manifest myoclonus and tonicclonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. Lafora disease frequently develops at 1018 years of age and tranmission is autosomal recessive.