The condition most commonly begins with epileptic seizures in late childhood or adolescence. Lafora disease ld, an autosomal recessive neurodegenerative disorder, is characterized by the presence of cytoplasmic polyglucosan inclusions known as lafora bodies in several tissues including the brain. It has an autosomal recessive mode of inheritance and is. Aug 29, 2012 lafora disease is a rare, fatal, autosomal recessive, progressive myoclonic epilepsy. Pdf files for printing pdf file size approximate download time over a 56k modem. Lafora disease ld is the most severe form of progressive myoclonus epilepsy with teenage onset.
Cancer, other pathologies, inflammation, immunity, infection, and aging, 2016. Structural biochemistrylafora disease wikibooks, open. Unlike most metabolic disorders, the link between lafora disease and metabolism has not been defined in almost 100 years. Lafora is a progressive and eventually fatal form of epilepsy. Check the status of your dogs dam, sire and known littermates on the kennel club test. Research open access loss of gabaergic cortical neurons. Lafora disease ld is a rare autosomal recessive disorder characterized by progressive myoclonic epilepsy followed by continuous neurological decline, culminating in death within 10 years. Laforas disease in an epileptic basset hound article pdf available in new zealand veterinary journal 382. Lafora disease ld is a recessively inherited teenage. Lafora disease neurology michigan medicine confluence. Lafora disease is a rare, fatal, autosomal recessive, progressive myoclonic epilepsy.
Several different types of seizures have been reported. Pdf lafora disease from pathogenesis to treatment strategies. 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. Typical polyglucosan bodies are present in the sweat gland lumina in laforas disease. Besides brain tissue, lafora bodies are found in muscles, skin, liver, and heart. Polyglucosan bodies are the pathologic hallmark of this. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin.
The health and welfare website of the uk dachshund breed council. In total, he published approximately 200 papers covering a wide range of subjects in neurology, psychiatry, and neuropathology. Frequently asked questions about the lafora screening programme. Lafora is an inherited disease, and is fairly rare as it takes two recessive genes. Genotypes and phenotypes of patients with lafora disease. 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, from 1982 to 1990. Lafora disease is a rare neurometabolic condition caused by a mutation in the epm2a andor epm2b genes.
Lafora epilepsy cure initiative, university of kentucky college of. Laforin and malin play a critical role in the survival of nerve cells neurons in the brain studies suggest that laforin and malin work together and may have several functions. Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. A form of stimulus sensitive myoclonic epilepsy inherited as an autosomal recessive condition. Lafora disease definition of lafora disease by medical.
Laforas bodies are present in the nervous system, and sometimes in the retina, heart, muscle, and liver. Histology of lafora bodies lafora bodies vary in size from 1 to 30 micron in diameter and one or more lafora bodies may be present in the cytoplasm. Genedx 207 perry parkway gaithersburg, md 20877 toll free. 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.
Smith, md \sb\laforas disease is a neurometabolic disease char acterized by progressive myoclonus epilepsy. Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. If your dog shows symptoms, alert the breeder of your dog now and get your dog tested as soon as possible. Lafora disease is the principal form of adolescenceonset progressive myoclonus epilepsy.
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. The diagnosis of lafora s disease is based on both clinical. Unlike most metabolic disorders, the link between lafora disease and metabolism has not been defined in. Medical and mental health complications of lafora disease. Laforas disease article about laforas disease by the free. Lafora disease in dogs symptoms, causes, diagnosis. Prior to the onset of symptoms, affected children appear to have normal development although some may have isolated febrile or nonfebrile convulsions in infancy or early childhood. The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of symptom onset. Targeting pathogenic lafora bodies in lafora disease using an. Lafora disease genetic and rare diseases information center. The condition is characterized by epilepsy, myoclonus and dementia.
Lafora disease patients with the malin protein defect live 25% long lives than patients with the laforin defect. Find support for a specific problem on the support section of our website. These mutations in either of these two genes lead to polyglucosan formation or lafora body formation in the cytoplasm of heart, liver, muscle, and skin. Lafora disease can be caused by defects in the epm2a gene, which. Diagnosis and genetic counseling are important aspects of ld, and social support is essential in disease management. Lafora disease is a fatal autosomal recessive form of progressive myoclonus epilepsy. Lafora disease and congenital generalized lipodystrophy. In total, he published approximately 200 papers covering a wide range of. The diagnosis of laforas disease is based on both clinical symptomatology and histologic detection of intra. Smith, md \sb\ lafora s disease is a neurometabolic disease characterized by progressive myoclonus epilepsy. The condition is characterised by a late onset of epilepsy, myoclonus and dementia. Primary symptoms of the pathology include seizures, ataxia, myoclonus, and progressive development of severe dementia. Aht presentation on lafora disease dachshund health uk. The most common presenting feature is a single seizure in the second decade of life.
Earlyonset lafora body disease differs from the progressive myoclonus epilepsies of unverrichtlundborg disease, lafora disease and sialidosis. Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures epilepsy and a decline in intellectual function. Lafora progressive myoclonus epilepsy lafora disease is a rare, usually childhoodonset, fatal neurodegenerative disease caused by biallelic mutations in epm2a laforin or epm2b nhlrc1. Progressive myoclonic epilepsies are characterized by the following. Our case expands the phenotype spectrum of lafora disease resulting. Targeting pathogenic lafora bodies in lafora disease. Described for the first time in 1911 by gonzalo rodriguez lafora 18861971 a spanish neurologist. Breed health plans, report on your dachshunds health, breed health survey data. Lafora disease genetic and rare diseases information. Genetic analyses have also identified two genes involved in glycogen storage as causative of the human disease. Lafora disease myoclonic epilepsy omim 254780 is a familial, degenerative disorder with the clinical triad of seizures, myoclonus, and dementia. Earlyonset lafora body disease brain oxford academic. Lafora disease ld is a severe form of epilepsy that manifests itself in teenagers and eventually leads to death. Typical progression of myoclonic epilepsy of the lafora type.
It is important to know that myoclonus is a clinical sign and not a disease. Although lafora disease appears as progressive myoclonic epilepsy, it is actually a glycogen metabolism disorder. Lafora disease is caused by lossoffunction mutations in epm2a or nhlrc1, which encode laforin and malin, respectively. Issn lafora disease ld is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus andor generalized seizures, visual hallucinations. Its etiopathological hallmark is the lafora body lb, present throughout the brain in profuse ever. Lafora progressive myoclonus epilepsy can be caused by mutations in either the epm2a gene or the nhlrc1 gene. It is this debilitation which frequently brings the parents of a lafora disease afflicted canine to a decision concerning possible euthanasia. Lafora disease from pathogenesis to treatment strategies. Aug 29, 2012 lafora bodies, in any case, have a major pathogenic role in lafora disease as evidenced by the demonstration that preventing lafora bodies formation, by reducing glycogen synthesis in laforindeficient mice, leads to disappearance of myoclonus and neurodegeneration, curing these mice from lafora disease turnbull et al. Muscle in lafora disease jama neurology jama network.
Its onset is earlier, one of its presenting symptoms, dysarthria, is not part of early phases of these diseases, and its myoclonus is somewhat less severe. As the disease progresses, the dogs experience other neurological problems, including dementia and difficulty walking. Progression of electroencephalography eeg changes in a patient with lafora disease. Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or.
Lafora disease ld is a rare, inherited, severe, progressive myoclonic epilepsy characterized. Sep 29, 2015 lafora disease is an inherited, severe form of progressive myoclonus epilepsy. Described for the first time in 1911 by gonzalo rodriguezlafora 18861971 a spanish neurologist. Patients manifest myoclonus and tonicclonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The epidemiology of lafora disease in germany is largely unknown. Nov 12, 2019 lafora progressive myoclonus epilepsy lafora disease is a rare, usually childhoodonset, fatal neurodegenerative disease caused by biallelic mutations in epm2a laforin or epm2b nhlrc1. Ld leads to accumulation of insoluble, abnormal, glycogenlike structures called lafora bodies lbs. At the age of 25, he had been diagnosed with juvenile myoclonic epilepsy. Dr rodriguez lafora was the first to describe lafora disease in 1911.
Other signs and symptoms include difficulty walking, muscle spasms myoclonus and demen. Isolation and preliminary characterization of lafora bodies in two cases. This is the first case report describing an association between congenital generalized lipodystrophy and. The objective of this retrospective case series is to characterize the genotypes and phenotypes of patients with 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. The two genes known to be involved in lafora disease are epm2a and nhlrc1 epm2b. A hallmark of ld is the accumulation of aberrant glycogen aggregates in brain and other tissues. Several works report that photoinhibition of ps ii is inversely proportional. A form of progressive myoclonic epilepsy, it can produce a variety of complications including intellectual disability, various seizure disorders, mental health. Most patients are completely normal in childhood, with the exception of early learning difficulties in some ganesh et al.
Typical progression of myoclonic epilepsy of the lafora. 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 disorder. Earliest symptoms are headaches, decline in school performance, spontaneous and induced myoclonus, and convulsive seizures, with eeg showing. Lafora disease is a hereditary epilepsy that is considered to be one of the progressive myoclonic epilepsies. The objective of this retrospective case series is to characterize the genotypes and phenotypes of patients with lafora. Pdf lafora disease ld is an autosomal recessive progressive myoclonus epilepsy due to mutations in the epm2a laforin and epm2b malin genes, with. It will, however, likely cause significant debilitation to your canine family member as the disease progresses. Laforas disease article about laforas disease by the. Lafora disease proteins malin and laforin are recruited to. Targeting pathogenic lafora bodies in lafora disease using.
Unusual course of lafora disease zutt 2016 epilepsia open. Washing in ethanol, drying, and manual application to carbon tape did not. Dachshund health information library dachshund health uk. What lafora disease is it is a progressive neurologic disease characterized by seizures, mioclonia, brain symptoms and psychic deterioration. Diabetes mellitus in a patient with lafora disease. Lafora disease was diagnosed based on skin biopsy results, which revealed pathognomonic lafora bodies. It is thought to be transmitted by autosomal recessive inheritance. He was best known now for describing in 1911 the intracytoplasmic inclusion bodies in lafora disease. Lafora disease in dogs, though a rare inherited disease, is not generally fatal for your pet. Lafora disease is a hereditary disorder and is known to be transmitted as an autosomal recessive pattern. Gonzalo rodriguez lafora 25 july 1886 27 december 1971 was a spanish neurologist. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. The most common feature of lafora disease is recurrent seizures. Lbs are overwhelmingly composed of an abnormally formed glycogen sakai et al, 1970 and likely.
The definitive place to find health and welfare information on dachshunds in the uk. Lafora disease can be caused by defects in the epm2a gene, which encodes the laforin protein phosphatase, or in the nhlrc1 gene also called. Other signs and symptoms include difficulty walking, muscle spasms myoclonus and dementia. Affected people also experience rapid cognitive deterioration that begins around the same time as the seizures. What lafora disease is it is a progressive neurologic disease characterized by seizures. Lafora disease epilepsy, progressive myoclonic, lafora. This is the first case report describing an association between congenital generalized lipodystrophy and lafora disease. The results of genetic analysis for mutations in epm2a and epm2b genes were negative. Some diseases are acute, producing severe symptoms that terminate after a short time, e. Lafora disease is a metabolic disorder resulting in insoluble glucan accumulation in the cytoplasm, and manifests as a debilitating neurodegeneration that ends with the death of the patient. It is a clinicopathologic form of unverrichts disease. Lafora disease is an autosomal recessive form of progressive myoclonic epilepsy caused by defects in the epm2a and epm2b genes. Lafora disease presentation, two cases in a mexican family.
It is caused by mutations in the gene encoding glycogen phosphatase epm2a or the e3 ubiquitin ligase. Glycogen is the sole carbohydrate storage molecule found in mammalian cells and plays an important role in cellular metabolism in nearly all tissues, including the brain. Adult polyglucosan body disease is a chronically progressive. These genes provide instructions for making proteins called laforin and malin, respectively. Treatment with metformin in twelve patients with lafora disease. It is thought to be transmitted by autosomal recessive inheri tance. With loss of function of either, structurally abnormal glycogen becomes insoluble and accumulates as lafora bodies, responsible for disease. Genetic analyses have also identified two genes involved. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for lafora disease.
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