Diabetes mellitus in a patient with lafora disease: Possible links with pancreatic β-cell dysfunction and insulin resistance

Ramona C. Nicolescu, Sara Al-Khawaga, Berge A. Minassian, Khalid Hussain

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Lafora disease (LD) is a rare autosomal recessive disorder characterized by progressive myoclonic epilepsy followed by continuous neurological decline, culminating in death within 10 years. LD leads to accumulation of insoluble, abnormal, glycogen-like structures called Lafora bodies (LBs). It is caused by mutations in the gene encoding glycogen phosphatase (EPM2A) or the E3 ubiquitin ligase malin (EPM2B/NHLRC1). These two proteins are involved in an intricate, however, incompletely elucidated pathway governing glycogen metabolism. The formation of EPM2A and malin signaling complex promotes the ubiquitination of proteins participating in glycogen metabolism, where dysfunctional mutations lead to the formation of LBs. Herein, we describe a 13-years-old child with LD due to a NHLRC1 (c.386C > A, p.Pro129His) mutation, who has developed diabetes mellitus and was treated with metformin. We discuss how basic mechanisms of LD could be linked to β-cell dysfunction and insulin resistance.

Original languageEnglish (US)
Article number424
JournalFrontiers in Pediatrics
Volume6
Issue numberJAN
DOIs
StatePublished - 2019

Keywords

  • Diabetes
  • EPM2A
  • EPM2B/NHLRC1
  • Glycogen metabolism
  • Insulin resistance
  • Lafora disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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