when should clinicians search for glut1 deficiency syndrome in childhood generalized epilepsies?

e u r o p e a n j o u rn a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 4 ) 1e6

Official Journal of the European Paediatric Neurology Society

Original article

When should clinicians search for GLUT1deficiency syndrome in childhood generalizedepilepsies?

S�ebastien Lebon a,*, Philippe Suarez b, Semsa Alija b, Christian M. Korff c,Jo€el Fluss c, Danielle Mercati d, Alexandre N. Datta e, Claudia Poloni a,Jean-Pierre Marcoz f, Ana Belinda Campos-Xavier b, Luisa Bonaf�e b,Eliane Roulet-Perez a

a Pediatric Neurology and Neurorehabilitation Unit, Department of Pediatrics, Centre Hospitalier Universitaire

Vaudois, Lausanne, Switzerlandb Centre for Molecular Diseases, Lausanne University Hospital, Lausanne, Switzerlandc Child Neurology, University Hospitals, Geneva, Switzerlandd Children's Hospital Neuchatel, Neuchatel, Switzerlande Pediatric Neurology and Development Unit, University Children's Hospital, Basel, Switzerlandf Children's Unit, Hopital du Valais, Sion, Switzerland

a r t i c l e i n f o

Article history:

Received 23 June 2014

Received in revised form

12 November 2014

Accepted 24 November 2014

Keywords:

GLUT1 deficiency

SLC2A1

Generalized epilepsy

* Corresponding author. Pediatric NeurologyVaudois (CHUV), 1011 Lausanne, Switzerlan

E-mail address: [email protected]

Please cite this article in press as: Lebongeneralized epilepsies?, European Journa

http://dx.doi.org/10.1016/j.ejpn.2014.11.0091090-3798/© 2014 European Paediatric Neuro

a b s t r a c t

GLUT1 deficiency (GLUT1D) has recently been identified as an important cause of gener-

alized epilepsies in childhood. As it is a treatable condition, it is crucial to determine which

patients should be investigated.

Methods: We analyzed SLC2A1 for mutations in a group of 93 unrelated children with

generalized epilepsies. Fasting lumbar puncture was performed following the identification

of a mutation. We compared our results with a systematic review of 7 publications of series

of patients with generalized epilepsies screened for SLC2A1 mutations.

Results:We found 2/93 (2.1%) patients with a SLC2A1mutation. One, carrying a novel de novo

deletion had epilepsy with myoclonic-atonic seizures (MAE), mild slowing of head growth,

choreiform movements and developmental delay. The other, with a paternally inherited

missense mutation, had childhood absence epilepsy with atypical EEG features and

paroxysmal exercise-induced dyskinesia (PED) initially misdiagnosed as myoclonic sei-

zures. Out of a total of 1110 screened patients with generalized epilepsies from 7 studies,

2.4% (29/1110) had GLUT1D. This rate was higher (5.6%) among 303 patients with early

onset absence epilepsy (EOAE) from 4 studies. About 50% of GLUT1D patients had abnormal

movements and 41% a family history of seizures, abnormal movements or both.

Conclusion: GLUT1D is most likely to be found in MAE and in EOAE. The probability of

finding GLUT1D in the classical idiopathic generalized epilepsies is very low. Pointers to

and Neurorehabilitation Unit, Department of Pediatrics, Centre Hospitalier Universitaired. Tel.: þ41 213143563; fax: þ41 213143572.(S. Lebon).

S, et al., When should clinicians search for GLUT1 deficiency syndrome in childhoodl of Paediatric Neurology (2014), http://dx.doi.org/10.1016/j.ejpn.2014.11.009

logy Society. Published by Elsevier Ltd. All rights reserved.

mailto:[email protected]

http://dx.doi.org/10.1016/j.ejpn.2014.11.009



e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 4 ) 1e62

Please cite this article in press as: Lebongeneralized epilepsies?, European Journa

GLUT1D include an increase in seizures before meals, cognitive impairment, or PED which

can easily be overlooked.

© 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights

reserved.

1. Introduction

Glucose transporter type 1 deficiency (GLUT1D) leads to

insufficient glucose for brain metabolism and has long been

associated with severe seizures, microcephaly, motor disor-

ders and developmental delay.1 Recently GLUT1D has been

identified as a cause of generalized epilepsies such as so-

called “idiopathic” generalized epilepsies (IGE), early-onset

absence epilepsy (EOAE) and epilepsy with myoclonic-atonic

seizures (MAE).2e5 Diagnosis is based on the presence of low

glucose in the cerebrospinal fluid (CSF),6,7 and a mutation in

SLC2A1 (solute carrier family 2 member 1) is found in the

majority of cases.1 The ketogenic diet (KD) or its modified

forms can usually control seizures and abnormal movements

and improve cognitive function.8e10 When seizures start in

infancy with an encephalopathic phenotype,11 they will

readily prompt a complete diagnostic work-up, but when they

present later as a generalized epilepsy, the challenge for cli-

nicians caring for children and adolescents is to decide which

patients should be investigated.

We screened SLC2A1 in a cohort of children and adoles-

cents with either new onset or established generalized epi-

lepsies according to clinical and electro-encephalographic

(EEG) features. Our findings were compared to a systematic

review of 7 cohorts of patients with generalized epilepsies

screened for SLC2A1 mutations from the literature.

2. Materials and methods

2.1. Patients

Patient data and blood samples were collected at the Lau-

sanneUniversity Hospital and other Swiss pediatric neurology

outpatient clinics (Geneva, Basel, Neuchatel, Sion, Luzern and

Zurich) between September 2011 and May 2013. Inclusion

criteria were: children and adolescents aged �18 years, a

diagnosis of generalized epilepsy on clinical and EEG criteria

(interictal or ictal generalized (poly-) spike and (poly-) spike-

waves). Exclusion criteria were focal epilepsies, symptomatic

epilepsies or the family refusal to participate in the study.

The protocol was approved by the ethics committees of all

participating centers. Informed consent from the parents or

legal guardian was obtained for all patients.

Probands were phenotyped including seizure, neurological

and developmental histories and examination by a pediatric

neurologist. Data were reported on a standardized form

including the following: family history of epilepsy or abnormal

movements, developmental history, learning disabilities,

abnormal movements, seizure manifestations, EEG findings

S, et al., When should cl of Paediatric Neurolog

and whether a diagnosis of GLUT1D was suspected before

enrolment.

2.2. Electroclinical definitions

Probands were categorized, whenever possible, into the clas-

sical idiopathic generalized epilepsy syndromes of childhood

absence epilepsy (CAE), juvenile absence epilepsy (JAE), juve-

nile myoclonic epilepsy (JME) and epilepsy with generalized

tonic-clonic seizure alone (EGTCA) according to the Interna-

tional League Against Epilepsy (ILAE) classification.12,13 For

instance, a patient was classified in the CAE group only when

he/she fulfilled the following: at least daily typical absences

accompanied by bilateral, regular, symmetric, generalized

3e4 Hz spike-waves with normal background on EEG, normal

development and neurologic examination.14 A child was

classified into the early onset absence epilepsy (EOAE) group

only when absence seizures started before four years of age

but otherwise fulfilled the criteria of CAE.

The generalized epilepsy syndrome of epilepsy with

myoclonic-atonic seizures (MAE) is characterized by afebrile

seizures starting between one and five years of age with

multiple seizures types including myoclonic-atonic, atonic, or

myoclonic seizures with or without generalized tonic-clonic

seizures, and absence seizures. One-third has earlier febrile

seizures. The EEG shows generalized spike- or polyspike and

wave discharges and often background slowing.15 Children

may have abnormal development prior to seizure onset or

present subsequent cognitive impairment.

Patients not fitting into MAE or classical IGE, such as those

with absence seizures with eyelid myoclonia (Jeavons syn-

drome) or a combination of absence, tonic-clonic, tonic or

atonic seizures, were denoted as unclassified IGE when

development and neurological examination were normal.

Patients with abnormal neurological findings and/or

abnormal development before seizure onset were classified

into generalized epilepsy of unknown origin. A fasting lumbar

puncture (LP) was performed in patients in whom a SLC2A1

mutation was found.

2.3. Systematic review

PubMed was searched by using the terms SLC2A1-gene and

epilepsy. Relevant references mentioned in the articles were

also included. Patients who were described in the literature

more than once were included only once. We focused on

publications reporting series of epileptic patients with

generalized seizures screened for SLC2A1 (Table 1) and looked

for features that may point to GLUT1D: additional seizures

type, movement disorders, family history of epilepsy,

linicians search for GLUT1 deficiency syndrome in childhoody (2014), http://dx.doi.org/10.1016/j.ejpn.2014.11.009



Table

1e

System

aticreview

oflitera

ture

cohortswithgenera

lize

depilepsiessc

reenedforSLC

2A1.

Auth

or

Selection

criteria

NPatients

GLUT1D

(SLC

2A1þ)

N(%

)Additionalfeatu

resofpatien

tswithGLUT1D

(SLC

2A1þ)

Additionalse

izure

types(N

)Movem

entdisord

ers

(N)

Fam

ilyhistory

(N)

Oth

ers

(N)

Suls

etal.3

EOAE

34

4(11.7)

GTCS(3),Myoclonic

seizure

(1)

Mildataxia

(2),PED

(1)

Epilepsy

(3)

ID(2)

Mullenetal.5

MAE

84

4(5)

no

Tremor(1),Dysa

rthria(3),

Ataxia

(2),PED

(2)

no

Cognitivedecline(2),

HCgro

wth

slowing(1)

Arsovetal.2

IGE

504

7(1.4)

Myoclonic

seizure

(1)

PED

(1)

Epilepsy

(2),PED

(2),

Epilepsy

þPED

(1)

no

Muhle

etal.19

EOAE/C

AE

þJA

E

26/124

2(7.7)/0

GTCS(1)

PED

(1),Ataxia

(1)

Epilepsy

(1)

ID(1)

Strianoetal.17

familialIG

E95pro

bands

1(1)

no

no

Epilepsy

þbord

erline

intellect

(1)

no

Arsovetal.4

EOAE

55

7(12.7)

GTCS(2)

PED

(1),Ataxia

(1)

Epilepsy

(1),PED

(1)

ID(2),DD

(1)

Agostinellietal.18

EOAE

188

4(2.1)

NA

NA

NA

NA

GTCS:generalize

dtonic

clonic

seizure,IG

E:idiopath

icgeneralize

depilepsy

,EOAE:earlyonse

tabse

nce

epilepsy

,CAE:ch

ildhood

abse

nce

epilepsy

,MAE:myoclono-atonic

epilepsy

,JA

E:juvenile

abse

nce

epilepsy

,PED:paro

xysm

alexercise-induce

ddysk

inesia,ID

:intellectualdisability,DD:developmentaldelay,NA:notavailable,HC:headcircumference

.

e u r o p e a n j o u rn a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 4 ) 1e6 3

Please cite this article in press as: Lebon S, et al., When should cgeneralized epilepsies?, European Journal of Paediatric Neurolog

abnormal movements or both and others neurological and/or

relevant developmental findings.

2.4. Genetic analysis

All samples were analyzed at the laboratory of the Centre

for Molecular Diseases at the Lausanne University

Hospital. Genomic DNA was extracted from peripheral blood

leukocytes using standard procedures. Primers for SLC2A1

were designed to cover all coding regions and intron-exon

boundaries (Ensembl access number, ENSG00000117394;

ENST00000426263). Fragmentswere amplifiedbyPCRandwere

sequenced on a 3500 Genetic Analyzer (Life Technologies).

Multiplex Ligation-dependent Probe Amplification (MLPA)was

performed on an ABI Prism 310 Genetic Analyzer (Life Tech-

nologies) according to the manufacturer's instructions.

3. Results

Ninety-three patients with generalized epilepsies were tested

for SLC2A1 mutations. Fifty-seven cases were recruited in

Lausanne and 36 in other Swiss centers. They all had gener-

alized seizures including absence, tonic-clonic, clonic, atonic

and myoclonic seizures, either alone or in combination.

Twenty-five patients had a family history of epilepsy and 1

had a family history of epilepsy and a movement disorder.

Eighty patients (86%) had IGEs: CAE in 14 of 93 (15%), EOAE in 4

of 93 (4.3%); JAE in 3 of 93 (3.2%), JME in 10 of 93 (10.7%), EGTCS

in 6 of 93 (6.4%), MAE in 26 of 93 (28%) and epilepsy with

myoclonic absences in 2 (2.1%). Unclassified IGE was diag-

nosed in 18 of 93 (19.3%) including 13 patients with a combi-

nation of absence and tonic-clonic seizures, 2 patients with

atypical absences with eyelid myoclonia (Jeavons syndrome),

two with absence epilepsy with photosensitivity, one with

reflex absence epilepsy. Ten of 93 (10.7%) had a generalized

epilepsy of unknown origin.

In 21/93 (22.5%) patients, GLUT1D was suspected by the

referring physician. Among them, 17 patients had IGEs

including 4 CAE, 1 JAE, 9 MAE, 3 unclassified IGE and 4

generalized epilepsies of unknown origin. Refractory seizures

were significantly more prevalent in these patients compared

to the group of patient not thought likely to have GLUT1D

(Fisher exact test, p ¼ 0.002).

SLC2A1 variants, including one not previously reported in

databases of human genetic variation, were identified in 2/93

patients (2.1%).

3.1. Patient 1

This boy had a heterozygous de novo deletion in exon 4 with a

frameshift leading to a premature stop codon (c.348delC;

p.Lys117Serfs*6). His family historywas unremarkable. He had

a few febrile seizures from 6 to 18 months. Then he had

multiple afebrile seizures including absence, myoclonic and

myoclonic-atonic seizures. EEGs showed 3e4 Hz generalized

spike and wave complexes activated by sleep on a slow

background. At 4 years, he had global developmental delay

with poor gross and fine motor skills and he was non-verbal.

Clinical examination revealed ataxia, brisk deep tendons





reflexes and choreiform movements. Mild deceleration of

head growth from the tenth to the third percentile was

observed. Magnetic resonance imaging (MRI) of the brain

showed delayed myelination of U-fibers in both fronto-

temporal areas. LP performed after only 2 h fasting showed

low cerebrospinal fluid (CSF) glucose at 2 mmol/L

(2.4e3.8mmol/L)16 and low CSF: blood glucose ratio of 0.4. The

KD was started and the child became seizure-free 1 month

later, withmarked improvement of his abnormal movements.

The seizures are now controlled for 2 years. The child remains

non-verbal with mild choreiform movements and ataxia.

3.2. Patient 2

The boywas seen at the age of 14 years for a second opinion on

familial generalized epilepsy and had a missense mutation in

exon 5. The heterozygous c.634C > T mutation changed an

arginine to a cysteine residue (p.Arg212Cys) andwas inherited

from his father. He had a history of jerks in the lower limbs

since the age of 4, which were first interpreted as epileptic

myoclonus. The patient reported involuntary jerks in both

lower limbs, often occurring when he felt hungry or after a

short walk before meal sometimes leading to falls. They were

actually paroxysmal dyskinesia triggered by hunger or exer-

cise on family videos. He developed brief episodes of absence

seizures with upward eye deviations at 7 years. The EEG

showed irregular (2e4 Hz) generalized poly-spike-waves on a

normal background. At 14 years, he had 2 generalized tonic-

clonic seizures triggered by exercise and delayed meals.

Symptoms and epileptiform discharges were overall carbo-

hydrate responsive. Wechsler Intelligence Scale for Children

Fourth Edition (WISC-IV) showed heterogeneous scores with a

verbal comprehension index (VCI) of 84, perceptual reasoning

index (PRI) of 65, working memory index (WMI) of 76, pro-

cessing speed index at 55 and learning difficulties. His father

had paroxysmal exercise induced dyskinesia (PED) of inde-

terminate age of onset and had no history of seizures. The

monozygotic father's twin-brother had epileptic seizures and

PED and his son (proband's cousin) had absences since the age

of 5 years with mild intellectual disability and PED. A fasting

LP showed a CSF glucose of 2.4 mmol/L and a CSF:blood

glucose ratio of 0.43, which were both below the tenth

percentile for the age.7 Six months after introduction of the

KD, the patient's seizures and PED were fully controlled and

this effect was sustained at 1 year follow-up.

3.3. Systematic review (Table 1)

The literature searched yielded a total of 7 articles describing

series of patients with generalized epilepsies and screened for

SLC2A1 mutations. Two studies ascertained patients for

IGEs,2,17 3 for EOAE,3,4,18 1 for EOAE and IGEs19 and 1 for MAE.5

Out of a total of 1110 patients screened for SLC2A1 mutations,

29 patients (2.6%) had GLUT1D. This rate was 2-fold higher

(5.6%, p¼ 0.01) among 303 patients from the 4 EOAE cohorts. In

this subgroup, additional seizures were reported in 35% (6/17).

There was a 5-fold increase risk to find GLUT1D in the EOAE

compared to the IGEs (17/303 versus 8/723 respectively, Fisher

exact test p< 0.001). Forty-five percent of GLUT1Dpatients had

abnormal movements, 41% had a family history of seizures,


abnormal movements or both. Twenty seven percent had

developmental delay/intellectual disability, but since these

studies were focusing on epilepsy and not cognition, this

value could have been underestimated.

4. Discussion

In our cohort of 93 children and adolescents with generalized

epilepsies, we found 2 patients (2.1%) harboring a SLC2A1

mutations. They were both suspected clinically to have

GLUT1D on the basis of history and clinical examination. In

terms of epilepsy syndrome classification, patient 1 has MAE

and patient 2 has unclassified familial IGE. No patient with a

classical IGE syndrome had GLUT1D.

Our cases illustrate two of the GLUT1D phenotypes, one

being close to the “classical developmental encephalopathy”,

and the second with a milder familial form.9,11 Patient 1 has a

previously unreported de novo deletion in exon 4 of SLC2A1,

leading to a premature stop codon in addition to the patho-

gnomonic finding of hypoglycorrhachia. The missense muta-

tion p.Arg212Cys in patient 2 has been previously described

and related to an early-onset severe phenotype, whereas our

case corresponds to a later-onset milder phenotype reported

by Leen et al.9

We are aware of the limitations and biases of our study: our

cohort of patients is small and we have a higher than usual

proportion of patients withMAE15: this is due to a referral bias,

since these patients are now increasingly being investigated

for GLUT1D and our study offered an opportunity for free

diagnosis. However, even if our cohort is not representative of

a wider population of generalized epilepsies, our patients

have been recruited from routine pediatric neurology outpa-

tient clinics, and the rate of 2.1% of GLUT1Dwas similar to that

found in our systematic review (2.4%; 2/93 versus 29/1110

respectively; Fisher exact test, p ¼ 1).

4.1. Generalized epileptic syndromes and GLUT1D

4.1.1. Epilepsy with myoclonic atonic seizures (MAE)GLUT1D was previously identified the cause of MAE in 4/84

patients.5 Our case had mild slowing of head growth and

choreiform movements; both are atypical features for MAE.

However, MAE patients can sometimes display multiple

segmental myoclonus responsible for an ataxic gait (“pseudo-

ataxia”) or choreiform movements. Therefore, identifying

signs specifically suggesting GLUT1D in MAE may be tricky.

Mullen et al. underline that 3 of their patients were undis-

tinguishable from “classical” MAE from the clinical and EEG

point of view.5We suggest to follow their recommendations to

search for GLUT1D in all patients with MAE.

4.1.2. Idiopathic generalized epilepsiesGLUT1D can cause IGE syndromes of JME, JAE and CAE.2,17,19 In

a recent study, Arsov et al. focused on a large cohort of 504

patients with IGE and found 7 (1.4%) patients with GLUT1D.

Among them, 1 had PED and 5/7 had a family history of epi-

lepsy, PED or both.2 PED may be mistaken for myoclonic sei-

zures as occurred in our patient 2. This diagnosis can easily be

missed in busy clinics. A careful description is essential, as




e u r o p e a n j o u rn a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 4 ) 1e6 5

well as a video whenever possible. In summary, the proba-

bility of finding a GLUT1D in patients with classical IGE syn-

dromes remains low, after a critical case review. This was

confirmed by Muhle et al. who did not find any positive pa-

tients in a cohort of 124 typical CAE and JAE.19

4.1.3. Early-onset absence epilepsyEOAE is the epilepsy category in which GLUT1D has been re-

ported in more than 10% of cases, and this finding was repli-

cated in 3 different studies (Table 1).3,4,19 Agostinelli et al.

recently studied a large cohort of 188 patients with EOAE in

whom SLC2A1 was screened, divided into “pure EOAE”

(n ¼ 111), adopting strict clinical and EEG criteria for CAE

except for the age of onset14 and “non pure EOAE” including all

other cases (n ¼ 77): 4/188 patients (2.1%) had GLUT1D and

were all part of the “non pure EOAE” group (4/77; 5.2%). The

authors concluded that patients with “pure EOAE” represent a

homogeneous group with favorable outcome whereas the

“non pure” group is heterogeneous, with various possible

underlying etiologies, among them structural abnormalities

and GLUT1D.18 Our 4 patients with EOAE were also “pure” and

had nomutation.When pooling 303 patientswith EOAE from4

studies,3,4,18,19 only 5% had GLUT1D which is lower than the

initial finding of 10%.3,4,19 Hence GLUT1D has to be searched

for in children with EOAE especially when abnormal devel-

opmental or neurological features or additional seizure types

like tonic-clonic and myoclonic seizures are found. An atyp-

ical EEG may be a further clue, since polymorphic and irreg-

ular discharges on an abnormal background have been

reported in GLUT1D with early onset absence seizures.20

4.2. Which patients to test and what test to perform?

Despite its apparent low rate as a cause of generalized epi-

lepsy, the issue of making a diagnosis of GLUT1D is critical

because of its implications for treatment and prognosis. This

can make a tremendous difference for patients as illustrated

by our two cases. KD and its variants are efficacious10 but may

however be difficult tomaintain in the long term, especially in

older children and adolescents. Since seizures are not always

refractory to AEDs and patients may only have minor cogni-

tive difficulties or movement disorders, the burden of the KD

may not seem justified.2,21 One may then ask if it is really

important to undertake costly genetic analyses for GLUT1D. Of

note, in milder forms of GLUT1D, seizures can decrease

spontaneously with age (sometimes with the later onset of

PED), suggesting that brainmaturation or other compensatory

mechanisms play a role that is not yet well understood.8 Mild

forms of GLUT1D seem not lead to cognitive decline during

adulthood.22

From our study and literature review, we suggest the

following recommendations: in generalized epilepsies, testing

for GLUT1D should be performed if seizures are not controlled

and if there is a developmental delay and/or a movement

disorder. Seizures before meals, and non-epileptic parox-

ysmal event triggered by fasting or exercise are good cues.11,23

A family history of movement disorder and/or seizures,

especially when suggesting autosomal dominant inheritance,

is also important.2,22 If the patient has a classical IGE


syndromewith controlled seizures, investigations for GLUT1D

are not indicated.

Hypoglycorrhachia being the distinctive biomarker for

GLUT1D, LP remains an easy, cheap and quick way to make

the diagnosis. However, CSF glucose level can be mildly low-

ered (2.2e2.8 mmol/l)6 especially in milder forms of GLUT1D.

On another hand about 5e10% of GLUT1D patients do not

carry a SLC2A1 mutation.24 Therefore, the combination of LP

and genetic testing is currently the most reliable diagnostic

approach. The discovery of hypoglycorrhachia in a patient

with refractory seizures and cognitive decline will allow rapid

initiation of the KD with the hope of improvement before the

genetic result is available. SLC2A1 sequencing can be pro-

posed first when seizures are less severe and treatment is less

urgent. It is likely that, with the rapid development of next

generation sequencing technologies becoming more and

more readily available and cheaper, the current recommen-

dations to search for GLUT1D will change over time.

Conflict of interest

None of the authors have any conflict of interest to disclose.

Acknowledgment

Wewould like to thank all participating family members. This

work was funded by the Research Funds of the Pediatric

Department at the Lausanne University Hospital. Christian M

Korff is supported by Swiss National Found 140332. We also

thank Dr J Kroell (Swiss Epilepsy Center, Zurich, Switzerland),

Dr T Schmitt-Mechelke (Children's hospital Lucerne,

Switzerland) and Dr AO Rossetti (Lausanne University hospi-

tal, Switzerland) for their participation to recruit patients. We

are very grateful to Dr Ingrid Scheffer for her helpful

comments.

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4. Arsov T, Mullen SA, Damiano JA, et al. Early onset absenceepilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia2012;53:e204e7.

5. Mullen SA, Marini C, Suls A, et al. Glucose transporter 1deficiency as a treatable cause of myoclonic astatic epilepsy.Arch Neurol 2011;68:1152e5.

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7. Leen WG, Wevers RA, Kamsteeg EJ, et al. Cerebrospinal fluidanalysis in the workup of GLUT1 deficiency syndrome: asystematic review. JAMA Neurol 2013;70:1440e4.


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when should clinicians search for glut1 deficiency syndrome in childhood generalized epilepsies?

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