Lafora disease, seizures and sugars

Division of Neurology, Krembil Neuroscience Centre, University of Toronto, Toronto Western Hospital, Toronto, Canada.
Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 08/2007; 26(1):83-6.
Source: PubMed


Lafora disease (LD) is the most severe form of Progressive Myoclonus Epilepsy with teenage onset. It has an autosomal recessive mode of inheritance and is almost universally fatal by the second or third decade of life. 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. This review will briefly address clinical issues and will focus on the molecular aspects of the disease.

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Available from: Danielle M Andrade
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    • "Mutation of the CBM20 abolishes the ability of laforin to bind to and to dephosphorylate glycogen [2]. Laforin, which is encoded by the EPM2A gene, was first identified in connection with a neurological disorder called Lafora disease, a fatal progressive myoclonus epilepsy with typical onset in the teenage years [24] [25] [26] [27]. Roughly half of the cases of Lafora disease result from mutations in the EPM2A gene. "
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    ABSTRACT: Glycogen, a branched polymer of glucose, is well known as a cellular reserve of metabolic energy and/or biosynthetic precursors. Besides glucose, however, glycogen contains small amounts of covalent phosphate, present as C2 and C3 phosphomonoesters. Current evidence suggests that the phosphate is introduced by the biosynthetic enzyme glycogen synthase as a rare alternative to its normal catalytic addition of glucose units. The phosphate can be removed by the laforin phosphatase, whose mutation causes a fatal myoclonus epilepsy called Lafora disease. The hypothesis is that glycogen phosphorylation can be considered a catalytic error and laforin a repair enzyme.
    Preview · Article · Sep 2011 · FEBS letters
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    • "In mice, phosphate introduced by glycogen synthase accumulates to a basal, tolerated level that remains constant from three to twelve months of age (Tagliabracci et al., 2008). When laforin is disabled in laforin knockout mice, however, excessive phosphorylation of glycogen occurs and is associated with a progressive deterioration in glycogen structure (Tagliabracci et al., 2008), leading ultimately to Lafora disease and its tragic consequences (Andrade et al., 2007; Delgado-Escueta, 2007; Gentry et al., 2009). It is interesting that, for the most part, laforin is restricted to vertebrates (Gentry et al., 2007), organisms with lifespans long enough for excessive phosphorylation of glycogen to have structural and metabolic consequences. "
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    ABSTRACT: Glycogen is a branched polymer of glucose that serves as an energy store. Phosphate, a trace constituent of glycogen, has profound effects on glycogen structure, and phosphate hyperaccumulation is linked to Lafora disease, a fatal progressive myoclonus epilepsy that can be caused by mutations of laforin, a glycogen phosphatase. However, little is known about the metabolism of glycogen phosphate. We demonstrate here that the biosynthetic enzyme glycogen synthase, which normally adds glucose residues to glycogen, is capable of incorporating the β-phosphate of its substrate UDP-glucose at a rate of one phosphate per approximately 10,000 glucoses, in what may be considered a catalytic error. We show that the phosphate in glycogen is present as C2 and C3 phosphomonoesters. Since hyperphosphorylation of glycogen causes Lafora disease, phosphate removal by laforin may thus be considered a repair or damage control mechanism.
    Preview · Article · Mar 2011 · Cell metabolism
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    ABSTRACT: Myoclonus is a brief shock-like movement that has many different etiologies. The degree to which it disturbs quality of life is extremely variable, as is its response to treatment. In this review, we focus on the treatment strategies for epileptic myoclonus in some common disorders, and in others that are not so common but where myoclonus is a prominent feature and has been studied more. An extended literature review in the English language was conducted through PubMed and text books. Epileptic myoclonus is a manifestation of cortical irritability. The precise etiology is important when determining the best course of treatment. Response to treatment is variable and usually depends on the epileptic syndrome. Some antiepileptic drugs may worsen myoclonus even in patients with syndromes where most patients have a good response to that same drug. Therefore, clinicians must always have in mind that worsening in myoclonus may be ameliorated by decrease or withdrawal rather than increase of medication.
    No preview · Article · Aug 2009 · Expert Opinion on Pharmacotherapy
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