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

1 Citation (Scopus)

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
Article number424
JournalFrontiers in Pediatrics
Volume6
Issue numberJAN
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Lafora Disease
Glycogen
Insulin Resistance
Diabetes Mellitus
Mutation
Progressive Myoclonic Epilepsy
Ubiquitin-Protein Ligases
Metformin
Ubiquitination
Phosphoric Monoester Hydrolases
Proteins
Genes

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Diabetes mellitus in a patient with lafora disease : Possible links with pancreatic β-cell dysfunction and insulin resistance. / Nicolescu, Ramona C.; Al-Khawaga, Sara; Minassian, Berge A.; Hussain, Khalid.

In: Frontiers in Pediatrics, Vol. 6, No. JAN, 424, 01.01.2019.

Research output: Contribution to journalArticle

@article{78f7acd898234707a135154636a6c0d8,
title = "Diabetes mellitus in a patient with lafora disease: Possible links with pancreatic β-cell dysfunction and insulin resistance",
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.",
keywords = "Diabetes, EPM2A, EPM2B/NHLRC1, Glycogen metabolism, Insulin resistance, Lafora disease",
author = "Nicolescu, {Ramona C.} and Sara Al-Khawaga and Minassian, {Berge A.} and Khalid Hussain",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fped.2018.00424",
language = "English",
volume = "6",
journal = "Frontiers in Pediatrics",
issn = "2296-2360",
publisher = "Frontiers Media S. A.",
number = "JAN",

}

TY - JOUR

T1 - Diabetes mellitus in a patient with lafora disease

T2 - Possible links with pancreatic β-cell dysfunction and insulin resistance

AU - Nicolescu, Ramona C.

AU - Al-Khawaga, Sara

AU - Minassian, Berge A.

AU - Hussain, Khalid

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Diabetes

KW - EPM2A

KW - EPM2B/NHLRC1

KW - Glycogen metabolism

KW - Insulin resistance

KW - Lafora disease

UR - http://www.scopus.com/inward/record.url?scp=85064322643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064322643&partnerID=8YFLogxK

U2 - 10.3389/fped.2018.00424

DO - 10.3389/fped.2018.00424

M3 - Article

VL - 6

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

SN - 2296-2360

IS - JAN

M1 - 424

ER -