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Review
. 2018 Dec;49(6):357-362.
doi: 10.1055/s-0038-1675238. Epub 2018 Oct 18.

Lafora Disease: A Review of Molecular Mechanisms and Pathology

Brandy Verhalen  1 , Susan Arnold  2 , Berge A Minassian  1   2
Affiliations
Review

Lafora Disease: A Review of Molecular Mechanisms and Pathology

Brandy Verhalen et al. Neuropediatrics. 2018 Dec.

Abstract

Lafora's disease is a neurodegenerative disorder caused by recessive loss-of-function mutations in the EPM2A (laforin glycogen phosphatase) or EPM2B (malin E3 ubiquitin ligase) genes. Neuropathology is characterized by malformed precipitated glycogen aggregates termed Lafora bodies. Asymptomatic until adolescence, patients undergo first insidious then rapid progressive myoclonus epilepsy toward a vegetative state and death within a decade. Laforin and malin interact to regulate glycogen phosphorylation and chain length pattern, the latter critical to glycogen's solubility. Significant gaps remain in precise mechanistic understanding. However, demonstration that partial reduction in brain glycogen synthesis near-completely prevents the disease in its genetic animal models opens a direct present path to therapy.

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Conflict of interest statement

Dr. Minassian reports grants from National Institutes of Health (NIH) during the conduct of the study; In addition, Dr. Minassian has a licensed Lafora's disease genes patent.

Figures

Fig. 1
Fig. 1
Lafora’s original drawings of Lafora bodies.
Fig. 2
Fig. 2
Wakeful EEC in a 17-year-old patient with LD and mutations in the EPM2A gene. Note the slow background and irregular generalized spike-wave discharges, e.g., in the last 4 seconds of the EEC page.
Fig. 3
Fig. 3
Skin biopsy from the same patient as above with periodic acid-Schiff staining. Arrows indicate pathognomonic Lafora bodies (LB) in the myoepithelia (at the bases) of apocrine sweat glands. Note, similarly stained structures near gland lumens(e.g., in the gland at the bottom left corner of the image). Those are the normal secretory products of these glands and are not LB. They are a common source of obviously highly undesired false-positive diagnosis in patients undergoing skin biopsy as part of a workup for progressive myoclonus epilepsy.
See this image and copyright information in PMC

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