"Lafora disease"

Gene therapy for Lafora disease in the Epm2a(-/-) mouse model. Lafora disease is a rare and fatal form of progressive myoclonic epilepsy typically occurring early in adolescence. The disease results from mutations in the EPM2A gene, encoding laforin, or the EPM2B gene, encoding malin. Laforin and malin work together in a complex to control glycogen synthesis and prevent the toxicity produced by misfolded proteins via the ubiquitin-proteasome system. Disruptions in either protein cause alterations in this complex, leading to the formation of Lafora bodies containing abnormal, insoluble, and hyperphosphorylated forms of glycogen. We used the Epm2a knock-out mouse model of Lafora disease to apply gene therapy by administering intracerebroventricular injections of a recombinant adeno-associated

Lafora Disease Masquerading as Hepatic Dysfunction Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present

Lafora Disease: A Ubiquitination-Related Pathology Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named Lafora bodies (LBs). LD is caused by mutations

A recurrent homozygous NHLRC1 variant in siblings with Lafora disease We report a case of two siblings with progressive myoclonus epilepsy whose parents were not consanguineous. Their clinical symptoms were typical of Lafora disease (LD), but skin biopsies revealed no Lafora bodies. Whole-exome sequencing identified a recurrent homozygous frameshift variant in the gene in both siblings

Extraneurological sparing in long‐lived typical Lafora disease Lafora disease (LD) clinically appears in previously healthy teenagers as progressively worsening seizures, myoclonus, dementia, and ultimately a vegetative state leading to death within a decade of its onset. Here we present a typical case of LD in which the patient survived until the age of 40. Although the patient's brain

Nationwide genetic testing towards eliminating Lafora disease from Miniature Wirehaired Dachshunds in the United Kingdom Canine DNA-testing has become an important tool in purebred dog breeding and many breeders use genetic testing results when planning their breeding strategies. In addition, information obtained from testing of hundreds dogs in one breed gives valuable information about the breed-wide genotype frequency of disease associated allele. Lafora disease is a late onset, recessively inherited genetic disease which is diagnosed in Miniature Wirehaired Dachshunds (MWHD). It is one of the most severe forms of canine epilepsy leading to neurodegeneration and, frequently euthanasia within a few years of diagnosis. Canine Lafora disease is caused by a dodecamer repeat expansion

Lafora disease - from pathogenesis to treatment strategies. Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of symptom onset. Lafora disease is caused by loss-of-function mutations in EPM2A or NHLRC1, which encode laforin and malin, respectively. The absence of either protein results in poorly branched, hyperphosphorylated glycogen, which precipitates, aggregates and accumulates into Lafora bodies. Evidence from Lafora disease genetic mouse models indicates that these intracellular inclusions are a principal driver of neurodegeneration and neurological disease. The integration of current knowledge on the function of laforin-malin as an interacting complex

Sodium selenate treatment improves symptoms and seizure susceptibility in a malin-deficient mouse model of Lafora disease. To search for new therapies aimed at ameliorating the neurologic symptoms and epilepsy developing in patients with Lafora disease. Lafora disease is caused by loss-of-function mutations in either the EPM2A or EPM2B genes. Epm2a and Epm2b mice display neurologic deficits and the sensitivity observed with pentylenetetrazol (PTZ) treatments in Epm2b mice. Neuronal degeneration and gliosis were also diminished after sodium selenate treatment. Sodium selenate could be beneficial for ameliorating some symptoms that present in patients with Lafora disease.

Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes (laforin

Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs

Lafora disease is an inherited metabolic cardiomyopathy

Diagnosis of Lafora Disease by Skin Biopsy

4-PBA and metformin decrease sensitivity to PTZ-induced seizures in a malin knockout model of Lafora disease Lafora disease (LD) is a rare adolescent-onset progressive myoclonic epilepsy caused by loss-of-function mutations either in the EPM2A gene encoding laforin or in the EPM2B gene encoding malin. Mouse models with deletion in the Epm2a or the Epm2b gene show intracellular aggregates

Everolimus does not prevent Lafora body formation in murine Lafora disease

A Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease This study will test the safety and efficacy of multiple doses of ION283 administered as intrathecal (IT) injections by lumbar puncture (LP). All subjects will receive ION283. The dose level of 15 mg will be studied in all subjects. A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients with Lafora Disease A single cohort will be evaluated in the study: N=10 • Initial dose of 15 mg ION283 intrathecal bolus (ITB) injection every 12 weeks. The study consists of 2 periods: * Screening Period: 4 weeks* Open label Treatment Period: 24 months

Efficacy and Tolerability of Perampanel in Ten Patients with Lafora Disease Lafora disease (LD) is a fatal intractable adolescence-onset progressive myoclonus epilepsy. Recently, two single-case studies reported drastic reductions in seizures and myoclonus with the AMPA antagonist perampanel and improved activities of daily living. We proceeded to study the effect of perampanel on 10 patients

Late-onset Lafora disease with prominent parkinsonism due to a rare mutation in EPM2A Lafora disease (LD) is an autosomal recessive form of progressive myoclonic epilepsy that is caused by mutations in EPM2A, encoding laforin, and NHLRC1 (EPM2B), encoding malin.(1) LD is classically described with onset in early teenage years. Patients develop myoclonus, epilepsy, visual hallucinations

NHLRC1 repeat expansion in two Beagles with Lafora disease Lafora disease is a fatal genetic disorder characterised by neurotoxic deposits of malformed insoluble glycogen. In humans it is caused by mutation in the EPM2A or NHLRC1 genes. There is a known mutation in miniature wirehaired dachshunds which has not been documented in other dog breeds, including beagles, in which the disease is relatively commonly reported. This case report describes the causative defect in two affected beagles, namely the same massive expansion as in miniature wirehaired dachshunds of a 12-nucleotide repeat sequence that is unique to the canine NHLRC1 gene. This is the first mutation described in beagles with Lafora disease, and so far the only Lafora disease genetic variant in dogs.

Lafora disease Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype-phenotype differences between the two. Founder effects and recurrent mutations are common, and mostly isolated to specific ethnic groups and/or geographical locations. Pathologically, LD is characterized

Unusual Course of Lafora Disease A 42-year-old male was admitted for refractory status epilepticus. At the age of 25, he had been diagnosed with juvenile myoclonic epilepsy. He had a stable clinical course for over a decade until a recent deterioration of behavior and epilepsy. After exclusion of acquired disorders, diagnostic work-up included application of next-generation sequencing (NGS ), with a gene panel targeting progressive myoclonic epilepsies. This resulted in the diagnosis Lafora disease resulting from compound heterozygous pathogenic variants. 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. Our case expands