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Lafora Disease

EPM2


Presentation

  • In present study, we reported two unrelated consanguineous Pakistani families with Lafora disease (Families A and B).[ncbi.nlm.nih.gov]
  • In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser(25) as the residue involved in this modification.[ncbi.nlm.nih.gov]
  • Four years after the first seizure the patient became bedridden, demented and presented with severe clinical condition. She died of pneumonia at age 20.[ncbi.nlm.nih.gov]
  • Abstract Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy.[ncbi.nlm.nih.gov]
  • Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation.[ncbi.nlm.nih.gov]
Wheelchair Bound
  • Over the following years, she became increasingly ataxic, lost bladder control, became mute by age 12 and wheelchair-bound by age 14.[doi.org]
Generalized Seizure
  • From Wikidata Jump to navigation Jump to search Lafora disease (LD) is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus and/or generalized seizures, visual hallucinations (partial occipital seizures), and progressive[wikidata.org]
  • Progressive Myoclonus Epilepsy (PME) of the Lafora type is an autosomal recessive disease, which presents in teenage years with myoclonia and generalized seizures leading to death within a decade of onset.[ncbi.nlm.nih.gov]
  • She developed normally until the age of 15, when she had her first occipital and generalized seizures. Four years after the first seizure the patient became bedridden, demented and presented with severe clinical condition.[ncbi.nlm.nih.gov]
  • Box plot showing the duration of induced partial seizures ( A ) and generalized seizures ( B ) observed in animals with indicated genotype.[doi.org]
Abnormal Gait
  • The mice did have neurological symptoms, including abnormal excessive scratching behaviour of neurological origin and in some an abnormal gait ( Ross et al. , 2012 ).[doi.org]
Gait Ataxia
  • He developed dysarthria, myoclonus and gait ataxia since primary school, and a generalized seizure at age 13. He reached secondary school but failed his GCSE (General Certificate of Secondary Education).[doi.org]
Alteration of Consciousness
  • The myoclonus becomes extremely frequent and is associated with alteration of consciousness interfering with every thought, resulting in frustration, itself worsening the myoclonus.[doi.org]
Screaming
  • She started experiencing hallucinations and paranoia, lost sphincter control and independent ambulation, became mute and at present commonly spends the entire night screaming loudly.[doi.org]
Onset in Late Childhood or Adolescence
  • It is an autosomal-recessive disorder with onset in late childhood or adolescence. Characteristic seizures include myoclonic and occipital lobe seizures with visual hallucinations, scotomata, and photoconvulsions.[ncbi.nlm.nih.gov]
  • Abstract Lafora's disease (LD) is an autosomal recessive and fatal form of epilepsy with onset in late childhood or adolescence.[ncbi.nlm.nih.gov]
  • Keywords BDNF Cerebral cortex GABAergic neurons Lafora disease Laforin Neurotrophin NGF p75NTR Background Lafora disease (OMIM 254780) is an autosomal recessive form of epilepsy with onset in late childhood or adolescence [ 1 – 3 ].[doi.org]
Onset in Late Childhood or Adolescence
  • It is an autosomal-recessive disorder with onset in late childhood or adolescence. Characteristic seizures include myoclonic and occipital lobe seizures with visual hallucinations, scotomata, and photoconvulsions.[ncbi.nlm.nih.gov]
  • Abstract Lafora's disease (LD) is an autosomal recessive and fatal form of epilepsy with onset in late childhood or adolescence.[ncbi.nlm.nih.gov]
  • Keywords BDNF Cerebral cortex GABAergic neurons Lafora disease Laforin Neurotrophin NGF p75NTR Background Lafora disease (OMIM 254780) is an autosomal recessive form of epilepsy with onset in late childhood or adolescence [ 1 – 3 ].[doi.org]

Workup

  • Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct.[ncbi.nlm.nih.gov]
Generalized Epileptiform Discharges
  • Diagnosis of Lafora disease was made on histo-pathological analysis of the skin biopsy, found positive for lafora bodies in periodic acid schiff stain and frequent generalized epileptiform discharges on electroencephalogram (EEG).[ncbi.nlm.nih.gov]

Treatment

  • Several therapeutic options for Lafora disease patients are currently being explored, and these therapies would benefit from a biochemical means of assessing functional laforin activity following treatment.[ncbi.nlm.nih.gov]
  • No preventative or curative treatment is currently available for LD and treatment focuses on palliation.[ncbi.nlm.nih.gov]
  • You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.[rarediseases.info.nih.gov]
  • In addition, we report the good effect of the Levetiracetam for the treatment of myoclonus in these patients, also demonstrated by the electrophysiological findings.[ncbi.nlm.nih.gov]
  • TREATMENT The primary focus of treatment is medication management for seizure control. Unfortunately, the disease is fatal and there is no specific treatment to "cure" the disorder.[thefreelibrary.com]

Prognosis

  • Abstract Lafora disease (LD) is an autosomal recessive, progressive disorder characterized by myoclonus and seizures, inexorable neurologic deterioration, cognitive decline and poor prognosis.[ncbi.nlm.nih.gov]
  • The disease has autosomal recessive inheritance, is progressive and the prognosis is poor.[ncbi.nlm.nih.gov]
  • Lafora's disease An AR neurometabolic disorder characterized by progressive myoclonus epilepsy and mental deterioration beginning in adolescence, ending in dementia Management Seizure control Prognosis Poor; death within 10 yrs of onset Lafora's disease[medical-dictionary.thefreedictionary.com]
  • Diagnosis - Lafora disease Prognosis - Lafora disease Not supplied. Treatment - Lafora disease There is no treatment, and therapy is mainly supportive and symptomatic.[checkorphan.org]
  • Drugs that are known to worsen myoclonus (i.e. phenytoin ) should be avoided. [2] [3] Last updated: 9/28/2015 The long-term outlook ( prognosis ) for people with Lafora disease is unfortunately poor.[rarediseases.info.nih.gov]

Etiology

  • In 183 short chapters, the book provides the essentials clinicians need on symptoms/signs, diagnostic tests, and neurologic disorders of all etiologies. For this edition, Timothy A.[books.google.com]
  • The etiology of Lafora disease and progression of the disorder are described. Implications for treatment of the disorder and palliative care are briefly discussed.[thefreelibrary.com]
  • However, the mechanism explaining laforin's role in the molecular etiology of LD is unknown. Fig. 1. A schematic of laforin and malin.[pnas.org]

Epidemiology

  • DISCUSSION: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD.[ncbi.nlm.nih.gov]
  • Cerebellar ataxia and/or involuntary movements Epidemiology Transmitted in an autosomal recessive fashion. Onset is in late childhood to adolescence (age 11 to 18 with a mean age of 14).[wiki.med.umich.edu]
  • Lamp-2 : Xq24 Phosphorylase (McArdle's), severe phenotype: 11q13 Triosephosphate isomerase : 12p13 Acid Maltase Deficiency (Glycogen storage disease 2 (GSD2); Pompe disease) Acid α-1,4-glucosidase (GAA) ; Chromosome 17q25.3; Recessive Nosology: LGMD 2V Epidemiology[neuromuscular.wustl.edu]
  • Life course epidemiology of trauma and related psychopathology in civilian populations. Curr Psychiatry Rep. 2015;17:31. 25. Bäärnhielm S, Laban K, Schouler-Ocak M, Rousseau C, Kirmayer LJ.[bjp.org.br]
  • The idea that mental illnesses could be uniformly formulated across the globe gained ground, thanks to epidemiological data and the “medicalization of psychiatry” movement, 48 among other reasons.[scielo.br]
Sex distribution
Age distribution

Pathophysiology

  • With a greater understanding of the pathophysiological processes involved, there is justified hope for future therapies.[ncbi.nlm.nih.gov]
  • In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown.[ncbi.nlm.nih.gov]
  • Pathophysiology A mutation in the EPM2A gene is the culprit in a majority of cases (80%). This gene encodes laforin, which is a tyrosine kinase inhibitor that plays a significant role in the regulation of glycogen metabolism.[wiki.med.umich.edu]
  • We described for the first time the pathophysiological role of p75NTR in Lafora disease; we showed an increase in the ICD-p75NTR levels.[doi.org]
  • Therefore, we reasoned that whether reducing glucose uptake in LD mice would ameliorate the disease pathophysiology.[doi.org]

Prevention

  • Furthermore, these data distinguish malin as an E3 Ub ligase whose activity is necessary to prevent a neurodegenerative disease that involves formation of nonproteinacious inclusion bodies.[ncbi.nlm.nih.gov]
  • Neuronatin is found to stimulate the glycogen synthesis through the activation of glycogen synthase and malin prevents neuronatin-induced glycogen synthesis.[ncbi.nlm.nih.gov]
  • To date, there is no prevention or cure. In the last decade, with the identification of the genes responsible for this disease, much knowledge has been gained with the potential for the future development of effective treatment.[ncbi.nlm.nih.gov]
  • Animal studies have shown that reducing the production of glycogen in neurons can prevent the disorder. Valerion’s goal is to enzymatically degrade neuronal glycogen, preventing its aggregation and rescuing the neurons from degeneration.[valerion.com]
  • Studies have shown that inhibition of glycogen synthesis in the brain could prevent the formation of Lafora bodies in the neurons and reduce seizure susceptibility in laforin-deficient mouse, an established animal model for LD.[ncbi.nlm.nih.gov]

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