Lafora disease in dogs symptoms, causes, diagnosis. Progressive myoclonic epilepsy journal of the neurological sciences. Pdf lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. Clinically it is characterised by generalised tonicclonic. Skin biopsies are reported with high sensitivity and specificity, observing inclusion bodies, and neurophysiological and electroencephalographic studies are undoubtedly nonspecific. It is a rare, autosomal recessive disease characterized by epilepsy, myoclonus, dementia and the presence of lafora bodies in various tissues 1,4. The last four traces are contralateral to first four. The beagle breed seems predisposed to a more severe type of lafora disease than other canine breeds and it seems that the beagle variety of the disease is more.
Veterinary pathology accumulation of laforin and other. 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 which is one of these 3 epilepsies in this group was described by lafora and glueck 1 in 1911. Nationwide genetic testing towards eliminating lafora. Miniature wirehaired dachshund breeder dianne graham of. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. While it can afflict any breed of canine, it seems to be most often found in the miniature wirehaired dachshund, basset hound and beagle breeds, with the beagle breed seeming to suffer more severe cases of it. Lafora disease is a fatal autosomal recessive, genetic disorder characterized by the presence of inclusion bodies, known as lafora bodies, within the cytoplasm. Lafora disease is fatal intractable progressive myoclonic epilepsy. Lafora disease is a fatal progressive myoclonus epilepsy. Epilepsy is one of the most frequent chronic neurological diseases in dogs affecting approximately 5 % of all dogs.
Disease progression was aggressive, with multiple generalised tonicclonic, myoclonic. The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of. Lbs induce neuronal apoptosis and are the causative agent of ld. Pdf the progressive myoclonic epilepsy of lafora or lafora disease ld is a neurodegenerative disorder characterized by recurrent seizures and. More than 90% of cases of lafora disease are due to mutations in epm2a coding for laforin protein and epm2b coding for malin protein. This is definitely a good thing as we can finally view pdf files without having to install thirdparty apps, but its more of a basic pdf reader. Pdf lafora disease from pathogenesis to treatment strategies.
Aug 01, 2015 skin inflammatory nontumor lafora body disease ld this website is intended for pathologists and laboratory personnel but not for patients. The disease is due to a mutation in the epm2b gene which results in intracellular accumulation of abnormal glycogen lafora bodies. Other signs and symptoms include difficulty walking, muscle spasms myoclonus and dementia. Lafora disease, is a rare, adultonset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually res. Lafora disease ld is a form of progressive my oclonic epilepsy, characterized by seizures, myoc lonus, dementia, and ataxia, with onset in adoles cence and progression to death within several years van heycop ten ham, 1968. Lafora disease ld is a recessively inherited teenageonset severe and fatal progressive myoclonus epilepsy. Structural mechanism of laforin function in glycogen. Researchers are searching for other genetic changes that may underlie this disease. Lafora disease is an uncommon genetic disorder characterized by progressive myoclonic epilepsy 1.
Lafora disease seizures electroencephalograph ygenetics. As noted above, lafora disease is a myoclonic epilepsy, meaning that it presents with jerking motions as its primary characteristic. Occipital independent multiple spikes are frequently observed and could correlate with the visual symptoms observated in the lafora disease. Omim 254780 is an autosomal within 510 years genton et al. Lafora disease five years ago when she discovered an english dog. It can be observed worldwide, but it is most commonly. Matthew gentry, director of the lafora epilepsy cure initiative leci and professor at the university of kentucky college of medicine. Fixed drug eruption caused by carbamazepine in a patient with.
Some 90% of the instances of lafora disease can be traced to mutations in. Eeg patterns orienting to lafora disease diagnosisa. 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. Lafora s disease is confirmed by mutation detection. Fixed drug eruption caused by carbamazepine in a patient. We have had to adopt a different way of living trying at all times to make adjustments that will. Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism disorder.
Most descriptions of the electroencephalogram eeg in ld have been isolated case reports. Glycogen phosphomonoester distribution in mouse models of the. Lafora disease, progressive myoclonus epilepsy, genetic study, prdm8, lafora bodies. Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures epilepsy and a decline in intellectual function. It was first described in 1911 by lafora and glueck in the brain and spinal cord of an adolescent patient who presented with a progressive and fatal form of myoclonic epilepsy 2. We herein report clinical and genetic findings of 26 italian ld patients.
Cureus lafora disease masquerading as hepatic dysfunction. Lafora disease ld is a devastating childhood epilepsy caused by intracellular, aberrant glycogen aggregates called lafora bodies lbs in the brain and other tissues. In humans also, another gene, laforin epm2a causes the disease, but epm2a has not been associated with it in dogs 17. Diagnosis by axilla skin biopsyin an early case of laforas disease. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that formswaterinsolubleinclusionscalledlaforabodies lbs. The disease usually manifests in previously healthy. Definitive diagnosis is made with biopsy showing typical spherical pas positive inclusion bodies.
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. Lafora dogs survey we have seldom seen anything in our mini wires more upsetting both for us and the dog. Clinical and genetic findings in 26 italian patients with. Generally, it comes on spontaneously after about the age of 5 years and is not gender specific. Lafora disease, which due to the symptomatology and the knowledge of the case we were able to detect her sisters disease. It is an autosomalrecessive disorder with onset in late childhood or adolescence.
Lafora disease ld is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature wirehaired dachshund. Glycogen phosphomonoester distribution in mouse models of. Pdf novel mutation in the nhlrc1 gene in a malian family. Mutations in the epm2a and nhlrc1 genes account for 80 percent to 90 percent of all cases of lafora progressive myoclonus epilepsy. In the remaining cases, the cause of the condition is unknown. Earlyonset lafora body disease brain oxford academic. The identification of this first binding partner for laforin promises to be an important step toward unraveling the underlying pathogenesis of this severest form of. Lafora disease is a fatal and rare autosomal recessive genetic disorder. It will not become clinically affected by the disease but, if bred to. It is an pme autosomalrecessive disorder with onset in late childarly adolescence.
Lafora disease affects a small number of people compared to the general population and is considered rare in many parts of the world. Because genetic heterogeneity in lafora disease has been described, mutational analysis of the epm2aip1 gene was performed on nonepm2a patients, but no mutations were found. Lafora disease is a rare, autosomal recessive, progressive myoclonic epilepsy with onset typically in the second decade of life and uniformly fatal outcome. Lafora disease genetic and rare diseases information center. Genetics of lafora lafora is an inherited autosomal recessive condition. Lafora epilepsy genetic test is accredited by the czech accreditation institute in compliance with iso17025. Generally, it starts at the end of childhood or during adolescence 6 to 20 years. Pdf lafora disease ld is an autosomal recessive late onset, progressive myoclonic epilepsy. Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or the entire body. Preclinical study of therapeutic strategy for lafora disease. Preclinical study of therapeutic strategy for lafora. Lafora disease ld is an autosomal recessive myoclonic epilepsy caused by mutations in the. Lafora disease in miniature wirehairs purina pro club.
Most of the current literature focuses on diagnosis, genetic basis, neurological signs, and possible treatment of this currently incurable disease. Lafora disease is a rare and fatal disease characterized by seizures. Autosomal recessively inherited progressive myoclonic epilepsy of lafora, which is also known as lafora disease ld. Seizure control and improvement of neurological dysfunction in. Lafora disease in miniature wirehaired dachshunds plos. Diagnosis of lafora body disease by axillary skin biopsy abstract. Defects in glycogen metabolism underlie the glycogen storage diseases gsds, genetic disorders with variable clinical phenotypes depending on the mutation type and affected genes. Genotypephenotype correlations suggested that epm2b patients show a slower course of the disease, with delayed age at death, compared with epm2a patients. Identification of a novel protein interacting with laforin. Lafora disease from pathogenesis to treatment strategies.
Lafora bodies and neurological defects in malindeficient. A dog that has only one mutated lafora gene is a carrier. Lafora disease ld is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Pdf writer create pdf documents from any windows application supports citrix metaframe, windows terminal server and windows 10, 8, 7, vista, xp, server 2019, 2016, 2012, 2008, 2008 r2, 2003, 2000. Lafora disease ld is a teenageonset fatal progressive myoclonus epilepsy caused by lossoffunction mutations in the epm2a gene.
Jul 30, 2016 microsoft edge is not only the default web browser in windows 10 but also the default pdf reader. Lafora disease ld is a form of progressive my oclonic epilepsy, characterized by seizures, myoc lonus, dementia, and ataxia, with onset in adoles. Lafora disease ld is a fatal, congenital, neurodegenerative epilepsy. Diagnosis of lafora body disease by axillary skin biopsy.
A dog must inherit two of the mutated genes, one from each parent to be classified affected. At root, it is due to constant acquisition of branches that are too long in a subgroup of glycogen molecules, leading them to precipitate and accumulate into lafora. Pdf writer windows 10, windows 8, windows server 2012. After onset, which usually occurs during late childhood or early adolescence, lafora disease is invariably fatal, typically within 10 years1,2. Ld epm2 resulting from a homozygous missense mutation in epm2b nhlrc1 was confirmed. Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. Mutations of various types were found in epm2a key words. Chelsea gerber is the inspiration behind chelseas hope, an organization dedicated to supporting awareness, research, treatment, and cures for those affected by lafora disease. Nationwide genetic testing towards eliminating lafora disease. In these patients, periodic acidschiff paspositive intracellular inclusion bodies, lafora bodies lbs, are the hallmarks of the disease.
Lafora disease is a rare, genetic, glycogen metabolism disorder inherited as. Lafora body disease is one of the inherited progressive myoclonic epilepsy syndromes. Ld manifests during adolescence with generalized tonicclonic seizures, myoclonus, absences, drop attacks or partial. A characteristic of the disease is the occurrence of deposits, called lafora bodies, in neurons, muscle, heart, skin and other tissues. Jul 25, 2019 a team of scientists have designed and tested in mice a novel and promising therapeutic strategy for treating lafora disease ld, a fatal form of childhood epilepsy. Lafora disease is a rare type of inherited epilepsy in canines which can occur in any canine breed but seems predisposed to miniature wirehaired dachshunds, basset hounds and beagles. 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. Lafora disease ld is a rare, fatal, lateonset, progressive form of myoclonic epilepsy, occurring in humans and dogs.
It is a progressive neurologic disease characterized by seizures, mioclonia, brain symptoms and psychic deterioration. Pdf lafora disease in miniature wirehaired dachshunds. Lafora body is a rarely seen and progressive disease which is characterized by mental decline, myoclonus and generalized epilepsy. Lafora disease is autosomal recessive progressive myoclonus epilepsy with late childhoodto teenageonset caused by lossoffunction mutations in either epm2a or epm2b genes encoding laforin or malin, respectively. Lafora disease ld is a teenageonset fatal progressive myoclonus epilepsy caused by lossoffunction mutations in the epm2a gene encoding the glycogen phosphatase laforin or epm2b encoding the laforininteracting ubiquitin e3 ligase malin. Minassian, md lafora s disease is one of five inherited progressive myoclonus epilepsy syndromes. Eeg in lafora disease is distinguished by an increased frequency of the spikewave complexes with disease progression. Chelsea passed away on december 19, 2016, following a 12 and half year struggle with the disease. Whole exome sequencing identified a novel missense mutation in. Footitt dr, quinn n, kocen rs, oz b, scaravilli f 1997 polyglucosans lafora disease. Lafora disease is a rare, autosomal recessive, progressive myoclonic epilepsy. Researchers coordinate efforts to find cure for lafora disease.
It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. Lafora disease in dogs is caused by a repeat expansion mutation in the nhl repeat containing e3 ubiquitin protein ligase 1 nhlrc1 gene 6, 8, a gene known to cause lafora disease in humans 16. Lafora disease ld is an autosomal recessive disorder that causes progressive structural epilepsy. In humans, ld isa fatal disease that has an onset in the. Characteristic seizures include myoclonic and occipital. Concerted actions of glycogen synthase gs and branching enzyme generate normal shortbranched soluble glycogen. Lafora progressive myoclonus epilepsy lafora disease ld is a fatal autosomal recessive neurodegenerative disorder characterized by the presence of glycogenlike intracellular inclusions called lafora bodies lbs 1 5.
The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of symptom onset. Among pmes, ld is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogenlike polyglucosan inclusions, named lafora bodies lbs. With disease progression, there is increased epileptiform activity, and a striking change in the spike. Laforas disease is a rare autosomal recessive disorder, the. The impact of lafora is enormous, both for our dogs 2 with the disease and ourselves. Gys1 antisense therapy rescues neuropathological bases of. Pdf novel mutations in epm2a and nhlrc1 widen the spectrum. Lafora disease is an inherited, severe form of progressive myoclonus epilepsy. N2 a 19year adolescent presented to a specialist hospital with a 5year history of lafora disease ld or progressive myoclonic epilepsy. Targeting pathogenic lafora bodies in lafora disease using. Longitudinal eeg studies in a kindred with lafora disease. After onset, which usually occurs during late childhood or early adolescence, lafora disease is invariably fatal, typically within 10.
Lafora disease ld, omim254780 is a rare and fatal form of progressive myoclonus epilepsy pme. Treatment with metformin in twelve patients with lafora disease. The condition most commonly begins with epileptic seizures in late childhood or adolescence. The patients 23yearold sister is wheelchair bound, has intractable myoclonic seizures and dementia, had lafora bodies in a skin biopsy, and had the same age of onset and mutation as her sister. Sep 29, 2015 lafora disease is an inherited, severe form of progressive myoclonus epilepsy. Lafora disease is caused by lossoffunction mutations in epm2a or nhlrc1, which encode laforin and malin, respectively. Targeting pathogenic lafora bodies in lafora disease using an. Ketogenic diet reduces lafora bodies in murine lafora disease. Lafora bodies contain a poorly branched glycogenlike substance, termed polyglucosan, which is hyperphosphorylated.
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