Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.


Journal

Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235

Informations de publication

Date de publication:
Aug 2020
Historique:
received: 27 11 2019
revised: 23 03 2020
accepted: 19 04 2020
pubmed: 12 5 2020
medline: 9 3 2021
entrez: 12 5 2020
Statut: ppublish

Résumé

Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far. Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions. We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet. Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

Sections du résumé

BACKGROUND BACKGROUND
Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.
CASE METHODS
Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions.
RESULTS RESULTS
We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet.
CONCLUSION CONCLUSIONS
Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

Identifiants

pubmed: 32389449
pii: S0387-7604(20)30126-1
doi: 10.1016/j.braindev.2020.04.008
pmc: PMC7906126
mid: NIHMS1669883
pii:
doi:

Substances chimiques

ALG3 protein, human EC 2.4.1.-
Mannosyltransferases EC 2.4.1.-

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

539-545

Subventions

Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : Medical Research Council
ID : MR/N025431/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N010035/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000848
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N025431/2
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Japanese Society of Child Neurology. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

C Paketci (C)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey. Electronic address: paketci@hotmail.com.

P Edem (P)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

S Hiz (S)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey.

E Sonmezler (E)

Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey.

D Soydemir (D)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

G Sarikaya Uzan (G)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Y Oktay (Y)

Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey; Department of Medical Biology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

E O'Heir (E)

Center for Mendelian Genomics and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, United States; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, United States.

S Beltran (S)

CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

S Laurie (S)

CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

A Töpf (A)

John Walton Muscular Dystrophy Research Centre, Institute of Translational and Clinical Research, Newcastle University and Newcastle Hospitals, Newcastle upon Tyne, United Kingdom.

H Lochmuller (H)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain; Children's Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.

R Horvath (R)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

U Yis (U)

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

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Classifications MeSH