Seizure: European Journal of Epilepsy 106 (2023) 8–13

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Seizure: European Journal of Epilepsy
journal homepage: www.elsevier.com/locate/seizure

The neuroimaging spectrum of SLC13A5 related developmental and
epileptic encephalopathy
Robyn Whitney *, Elaine Choi, Kevin C. Jones
Division of Neurology, Department of Paediatrics, McMaster University, 1200 Main Street West, Hamilton, ON, Canada

A R T I C L E I N F O

A B S T R A C T

Keywords:
SLC13A5 gene
Neuroimaging
Developmental and epileptic encephalopathy
Punctate white matter lesions
Genetics

Background: SLC13A5 related developmental and epileptic encephalopathy (DEE) is an autosomal recessive
condition characterized by neonatal seizures, fever sensitivity, status epilepticus, developmental delay and tooth
anomalies. The neuroimaging spectrum of SLC13A5 related DEE is not fully known. We present a case of
SLC13A5 related DEE with distinct neuroimaging findings and review the neuroimaging findings of all published
cases of SLC13A5 related DEE.
Methods: A retrospective case review and focused review of the literature was completed.
Results: A 16-month-old male with a clinical phenotype consistent with SLC13A5 related DEE and a previously
reported pathogenic variant in SLC13A5, c.655G>A, p.Gly219Arg and a novel likely pathogenic variant in
SLC13A5, c.202C>T, p.Pro68Ser was identified. MRI at day 5 of life revealed wide spread punctate white matter
lesions (PWMLs) affecting the subcortical white matter, periventricular white matter, splenium of the corpus
callosum, posterior limb of the internal capsule, corticospinal tracts, midbrain, pons and medulla, mimicking a
metabolic/infectious etiology. MRI at one month showed atrophy and evolution of white matter necrosis. One
hundred and five cases of SLC13A5 related DEE were identified. Initial MRI was completed in 62 cases (59%).
MRI was normal in 41 cases (66%) and abnormal in 21 (34%). White matter abnormalities were most common
(n=15, 71%); PWMLs occurred in 8 cases (38%).
Conclusion: Neuroimaging abnormalities may exist in a third of SLC13A5 related DEE cases. White matter ab­
normalities such as PWMLs appear most common. It remains unknown why some are susceptible to these lesions
and how they affect long-term neurodevelopmental outcomes in SLC13A5 related DEE.

1. Introduction
Monogenic etiologies of epilepsy, including developmental and
epileptic encephalopathies (DEEs), have been increasingly recognized
over the last decade and up to 50% of epilepsies may now have an
identifiable genetic cause [1–3]. Mendelian inheritance constitutes
approximately 1% of these cases [1–3]. A number of different disease
mechanisms are implicated in genetic epilepsies [4]. Recently,
dysfunction in solute carriers (SLCs), which are involved in the transport
of solutes across the blood brain barrier, astrocytes, oligodendroglia
cells and neurons have been implicated in neurological disorders
including DEEs [5].
SLC13A5 encodes for the plasma membrane sodium coupled citrate
transporter (SLC13A5) and is expressed in the brain, liver, tooth cells
and testes. In the central nervous system, the SLC13A5 transporter is
expressed mostly in neurons, and its role is to uptake both circulating

citrate and citrate released by astrocytes for metabolism [6–8]. The
mechanism by which dysfunction of the SLC13A5 transporter results in
neurological disease is unknown [7,9,10]. However, citrate is the main
intermediate of the tricarboxylic acid (TCA) pathway and deficiency of
citrate due to impaired transporter function could result in energy fail­
ure [9–11]. Citrate is also involved in the synthesis of
gamma-aminobutyric acid (GABA) and glutamate, so transporter
dysfunction could lead to an imbalance of neurotransmitters (i.e.,
excitatory versus inhibitory) [10,11]. Alterations in brain citrate meta­
bolism may also lead to a propensity for seizures and cause neuronal
network hyperexcitability, as shown in a recent mouse model [7].
In humans, autosomal recessive pathogenic variants in SLC13A5
cause a rare DEE with onset in the neonatal period [12–15]. SLC13A5
related DEE is characterized by seizures within the first week of life,
fever sensitivity with recurrent status epilepticus (most commonly
generalized tonic-clonic seizures (GTCs)), moderate to severe

* Corresponding author.
E-mail address: whitner@mcmaster.ca (R. Whitney).
https://doi.org/10.1016/j.seizure.2023.01.014
Received 22 October 2022; Received in revised form 14 December 2022; Accepted 18 January 2023
Available online 23 January 2023
1059-1311/Crown Copyright © 2023 Published by Elsevier Ltd on behalf of British Epilepsy Association. This article is made available under the Elsevier license
(http://www.elsevier.com/open-access/userlicense/1.0/).

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Seizure: European Journal of Epilepsy 106 (2023) 8–13

intellectual disability, movement disorders, and other systemic features
such as tooth abnormalities (i.e., hypodontia), growth attenuation and
cardiorespiratory anomalies [10–15]. Presently there are no targeted
therapies available for SLC13A5 related DEE [10]. The EEG findings in
SLC13A5 related DEE have been previously summarized and range from
normal recordings to background slowing and/or generalized and
multifocal interictal epileptiform discharges (IEDs) [16]. The neuro­
imaging features have not been fully elucidated, but may be normal or as
recently described may show a unique pattern of punctate white matter
lesions (PWMLs) [10,11,13,15]. Herein, we report a previously unpub­
lished compound heterozygote case of SLC13A5 related DEE with widely
distributed white matter lesions, mimicking an underlying infectious/­
metabolic etiology. We highlight the signature neuroimaging phenotype
of SLC13A5 related DEE and summarize all previous published neuro­
imaging findings in SLC13A5 related DEE (Table 1).

Table 1
Neuroimaging findings of previously reported cases of SLC13A5 DEE.
Study
Number

Number of
Cases

MRI Onset::

MRI Follow up:

Reference

1

14
*3 cases in
this study
were
reported
by Hardies
et al. [13]
(Family B
and D –
initial MRI
normal in
all)
*1 case in
this study
was
reported
by Weeke
et al. [11]
(Family 5 –
initial MRI
PWML,
resolved
on follow
up).

Normal (n=13),
abnormal (n=1)
PWML (n=1)
(resolved on
follow up)

Matricardi
et al. [15]

2

1

Normal (n=1)

First epoch (0-3
years), repeat
MRI (n=11)
MRI normal
(n=7),
hyperintensity
periventricular
WM (3) and
corpus callosum
hypoplasia (n=1)
Second epoch
(>3-6 years),
repeat MRI (n=4)
Hyperintensity
periventricular
WM (n=1), mild
corpus callosum
hypoplasia (n=3)
Third epoch (>612 years), repeat
MRI (n=4)
Hyperintensity
periventricular
WM (n=1), mild
corpus callosum
hypoplasia (n=3)
Fourth epoch
(>12-18 years),
repeat MRI (n=2)
Cortical atrophy
(n=2)
Fifth epoch (> 18
years), repeat
MRI (n=2)
Cortical atrophy
(n=2)
Not reported

3

8

Normal (n=0),
abnormal (n=7)
PWML (n=6)
N=1 had high
signal intensity
in WM on T2
MRI, suspected
PWML, small
tentorial SDH,
low NAA/Cho
ratio and small
lactate peak in
WM. No follow
up MRI as
deceased.

4

15

Not reported

5

1

Hyperintensity
left occipital
cortex (n=1)

6

23

Not reported

2. Materials and methods
A retrospective chart review was completed after consent was ob­
tained from the patient’s caregivers as per the local research ethics
guidelines. The American College of Medical Genetics (ACMG) criteria
were used to classify the SLC13A5 variants [17]. We also conducted a
focused comprehensive narrative literature review of previously re­
ported SLC13A5 related DEE cases. PubMED, Web of Science, and Sco­
pus were searched until October 11, 2022 using the following terms:
SLC13A5, SLC13A5 seizures, SLC13A5 epilepsy and SLC13A5 DEE.
Publication citations were screened to look for additional cases and
duplicate cases. All cases of SLC13A5 related DEE were then collected
and data regarding the neuroimaging findings were manually extracted
and summarized (Table 1).
3. Results
3.1. Case description
A now-16-month-old male was born at 38 weeks via an uncompli­
cated vaginal delivery to a non-consanguineous couple. He presented
with multifocal seizures on the first day of life. Seizures were initially
characterized by gaze deviation, jitteriness, and stiffening movements.
Family history was non-contributory. Video EEG (vEEG) showed
multifocal electrographic seizures, discontinuity, and multifocal IEDs. A
number of anti-seizure medications (ASMs) were tried including a
midazolam infusion, phenytoin, lacosamide, folinic acid and pyridoxal5-phosphate. MRI at day 5 of life showed multiple areas of restricted
diffusion as well as T1 hyperintensity and T2 hypointensity (PWMLs) in
the bilateral parasagittal, frontoparietal, temporal, occipital and peri­
ventricular white matter, as well as the splenium, posterior limb of in­
ternal capsule (PLIC), corticospinal tracts, tegmentum of the midbrain,
anterior pons and medulla (Fig. 1). A diagnosis of an underlying meta­
bolic, hypoxic ischemic or infectious etiology was suspected; however,
extensive metabolic and infectious work up was negative, and birth
history was not consistent with hypoxic-ischemic injury. Comprehensive
epilepsy gene panel revealed a previously reported pathogenic variant in
SLC13A5, NM_177550.4: c.655G>A, p.Gly219Arg and a novel variant of
unknown significance in SLC13A5, NM_177550.4: c.202C>T, p.
Pro68Ser, inherited each from one parent. Using the ACMG criteria, we
reclassified the VUS as likely pathogenic [17] (Table 2).
Repeat MRI was completed at 1 month due to recurrent seizures. MRI
showed parenchymal atrophy involving the bilateral frontoparietal and
temporal lobes. The high TI signal in the deep and subcortical white
matter was still present, but less conspicuous. There was no restricted
diffusion, and myelination was appropriate (Fig. 1). Overall, the MRI
was felt to show evolution of white matter parenchymal necrosis. vEEG
at 1 month of age showed a discontinuous background with multifocal
IEDs and seizures with subtle clinical signs (i.e., eye opening, chewing)
from the temporal head regions. Maintenance phenobarbital and

Deceased (n=4)
with no follow up,
follow up MRI
completed (n=4)
Follow up MRI
(n=4):
MRI at 6 and 18
mths (n=2):
Delayed
myelination,
gliosis, WM loss
(previous PWML)
MRI at 13 mths
(n=1): Normal
(previous PWML)
One case no
initial MRI, but
MRI at 11, 16, 3
years and 6 years
(n=1): Delayed
myelination,
gliosis, WM loss
Not reported
At 4mths:
bilateral cortex
hyperintensities,
reduced
myelination
(n=1)
At 6 mths:
atrophy, corpus
callosum thinning
(n=1)
Not reported

Santalucia et al.
[8]
Weeke et al.
[11]

Brown et al.
[18]
Pellegrino et al.
[20]

(continued on next page)

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Seizure: European Journal of Epilepsy 106 (2023) 8–13

Table 1 (continued )
Study
Number

7

8

Number of
Cases

5
*2 cases in
this study
were
described
by Klotz
et al. [14]
(Family A,
both (n=2)
with
normal
MRI)
9

9

8

10

7

11

10
*3 cases in
this study
were
described
by Hardies
et al. [13]
(Family C,
all with
normal
MRI)

12

3

13

2

14

3

Table 1 (continued )
MRI Onset::

Normal (n=3),
abnormal (n=2)
PVL (n=1)
Chiari 1
malformation
(n=1)

MRI Follow up:

Not reported

Reference

Number of
Cases

Yang et al.
[16]
Bainbridge
et al. [9]

MRI normal
(n=6),
abnormal (n=3)
Frontal lobe
thickening
(n=1)
Hyperintense
WM lesion in
parietal lobe
(n=1)
Focal loss of GM
(n=1)
MRI normal
(n=6),
abnormal (n=
2)
PVL like (n=1)
Multiple PWML
and elevated
lactate (n=1),
follow up at 6
mths and 14
mths.
MRI non
conclusive/
normal for all
subjects (n=7)
MRI normal
(n=9),
abnormal (n=1)
Mild atrophy
left hemisphere
(n=1)

Not reported

MRI normal
(n=2),
abnormal (n=1)
Posterior
periventricular
hyperintensity
with reduction
of volume of
WM (n=1)
Normal (n=0),
abnormal (n=2)
Delayed
myelination
(n=1)
FCD (n=1)

Not reported

Alhakeem et al.
[19]

Delayed
myelination
resolved (n=1)
FCD persisted
with residual
abnormality in
the right frontal
parietal region
extending to the
periventricular
WM (n=1)
Not reported

Anselm et al.
[22]

MRI abnormal
(n=1),

Study
Number

Klotz et al.
[14]

MRI at 6 mths
(n=1), brain
atrophy, loss of
WM at 14 mths no
progression
(initial MRI had
shown PWML)

Hardies et al.
[13]

Not reported

Thevenon et al.
[12]

Not reported

Schossig et al.
[21]

MRI Onset::

MRI Follow up:

Reference

Not reported

Arvio et al.
[24]
Pantoja Leao
et al. [25]
Mir et al. [5]
SnoeijenSchouwenaars
FM et al. [26]

15

2

unavailable
(n=2)
Non-specific
enlargement of
subarachnoid
spaces
Not reported

16

1

Normal (n=1)

Not reported

17
18

1
1

PVL (n=1)
Normal (n=1)

Not reported
Not reported

Legend: FCD: Focal cortical dysplasia, GM: grey matter, MRI: magnetic reso­
nance imaging, Mths: months, N: number, PVL: periventricular leukomalacia,
PWML: punctate white matter lesions, Sz: Seizure, SDH: subdural hematoma,
WM: white matter

levetiracetam were added to lacosamide. EEG at 6 months showed a
normal background and was mildly abnormal due to runs of diffuse
polymorphic delta activity.
At follow up at 16 months of age, the child was having weekly sei­
zures (i.e., generalized tonic, generalized tonic-clonic and focal motor
onset with impaired awareness seizures) of variable duration, <1 min to
9 min. He also had tonic-clonic convulsive status epilepticus triggered by
febrile illness/immunization. Maintenance ASMs included clobazam,
topiramate, levetiracetam, phenobarbital, and lacosamide. Develop­
mentally, he had head control and was working on rolling and sitting. He
could grab objects, vocalize, understand his name, and visually track
parents. Medical history was complicated by hypotonia, decreased
enamel, gastrointestinal reflux, G-tube feeding, obstructive sleep apnea
(OSA) and movement disorder (i.e., tongue twitching/thrusting and
excessive movements of extremities). On neurological exam there was
mild axial hypotonia with no focal findings.
3.2. Literature review
A total of 105 cases with SLC13A5 related DEE from 18 articles were
included (Table 1) [5,8,9,11–16,18–26]. Duplicate cases were identified
in study 1, 7 and 11 (Table 1) [9,15,21]. An initial MRI around the time
of presentation was available in 62 cases (59%). Initial MRI was normal
in 41 cases (66%) and abnormal in 21 cases (34%). Of the cases with
abnormalities (n=21), the findings included: PWMLs or suspected
PWMLs (n=8, 38%), hyperintense lesion within the white matter (i.e.,
parietal lobe, occipital lobe, or periventricular area) (n=3, 14%), peri­
ventricular leukomalacia (PVL) (n=3, 14%), delayed myelination (n=1,
5%), and other findings (n=6, 29%) such as frontal lobe thickening
(n=1, 5%), focal loss of grey matter (n=1, 5%), mild atrophy of the left
hemisphere (n=1, 5%), focal cortical dysplasia (FCD) (n=1, 5%),
enlargement of the subarachnoid spaces (n=1, 5%), and Chiari 1 mal­
formation (n=1, 5%) [5,9,11,13–15,19–23] . Repeat brain MRI was
seldom completed and findings on follow up are summarized in Table 1
[11,13,15,20,22]. There were 4 cases with PWMLs who had follow up
imaging, and in 3 cases imaging subsequently showed white matter loss,
gliosis, and delayed myelination, while in 1 case the findings had
resolved [11,13]. Other findings seen on follow up MRI were corpus
callosum hypoplasia/thinning, hyperintensity within the periventricular
white matter, brain atrophy, persistent FCD, and bilateral hyper­
intensities within the cortex with reduced myelination [11,15, 20,22].
4. Discussion

Duan et al.
[23]

In summary, we report a new case of SLC13A5 related DEE and
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Fig. 1. Representative neuroimaging findings of our case: MRI images A-H at day 5 of life show PWMLs with restricted diffusion on DWI sequence throughout the
cortical and subcortical white matter, optic radiations, posterior limb of internal capsule, splenium, corticospinal tract, midbrain, pons, temporal lobes and medulla.
Image I shows that there is corresponding dark signal on ADC map. Images J to L show subtle increased T1 signal throughout the subcortical white matter (see
arrows). Image M shows T2 MRI with subtle decreased T2 signal (see arrow). MRI images N-P at 27 days of life show subtle increased T1 signal is seen in the white
matter (Images N-O, arrow), ventricular enlargement and non-specific T2 patchy signal in the white matter as well as diffuse parenchymal atrophy (Image P).

highlight the neuroimaging phenotype of this condition via illustration
of an additional case and literature review. Our case presented with a
similar clinical phenotype as described in the literature with neonatal
onset seizures, subsequent fever sensitivity with status epilepticus,
developmental delay, hypotonia, movement disorder, and decreased
enamel. EEG initially showed multiple electrographic seizures, discon­
tinuous background and multifocal IEDs, but by six months had nearly
normalized [5,8,9,11–16,18–26]. Normalization of the EEG background
and interictal pattern has been described previously with
SLC13A5-related DEE [16]. Initial MRI showed wide spread PWMLs
scattered throughout the subcortical white matter and periventricular
area, but also extending to the corpus callosum, corticospinal tracts,
midbrain, pons and medulla. Follow up MRI at one month showed

atrophy and evolution to white matter necrosis. Although PWMLs have
been described before with SLC13A5-related DEE predominantly in the
subcortical white matter and periventricular regions, we are unaware of
previous cases showing such an extensive topographic distribution of
PWMLs. In our case, PWMLs were widespread affecting the subcortical
and periventricular white matter regions, but also extending to multiple
regions in the brainstem, prompting consideration of a possible meta­
bolic and/or infectious etiology [11,13]. We also provide insight into the
other neuroimaging findings observed in SLC13A5 related DEE.
The MRI findings of SLC13A5 related DEE reported in the literature
are variable [5,9,11,13–15,19–23]. Initial MRI is normal in two thirds of
cases, while abnormalities exist in a third. When grouped together,
white matter abnormalities are most commonly observed (n=15, 71%)
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may also be important, for instance PWMLs within the PLIC or corti­
cospinal tract may predict risk of motor impairment [11,27–28]. The
first association between SLC13A5 related DEE and PWMLs was
described by Weeke et al. [11], although few other cases have been
reported [13]. In the limited existing cases with follow up imaging (i.e.,
at 6 to 18 months), successive MRI of patients with PWMLs has shown
permanent injury with white matter loss, gliosis and delayed myelina­
tion [13]. Likewise, our case had repeat MRI at one month of age which
also showed atrophy and white matter injury, however further follow up
neuroimaging studies have not been completed. Currently it is unknown
whether patients with PWMLs with SLC13A5 related DEE have different
neurodevelopmental outcomes than patients without white matter
injury, which may be an area of future study.
It is unknown why some patients with SLC13A5 related DEE are
susceptible to PWMLs and other forms of white matter injury while
others are not. As previously discussed, citrate is the main intermediate
of the TCA cycle, and deficiency of citrate in SLC13A5 related DEE may
lead to energy failure within the central nervous system [9–11]. Inter­
estingly, the ketogenic diet has been proposed as a treatment option to
bypass this deficiency, although has had mixed results in SLC13A5
related DEE to date [10,13]. Larger studies are needed to determine the
effectiveness of the ketogenic diet in this condition. It is possible that
frequent prolonged seizures, coupled with low citrate, could predispose
to injury (i.e., due to excess metabolic stress) and PWMLs in some pa­
tients [11]. However, seizure burden is generally higher in the neonatal
period for most cases of SLC13A5 related DEE, yet many still have
normal neuroimaging [9,12,14,15,19,21,25,26]. Whether some geno­
types are more at risk for white matter injury is also unclear at this time,
given the small number of cases of SLC13A5 related DEE reported. It has
also been suggested that patients with SLC13A5 related DEE may be
more susceptible to ischemic injury and thus predispose them to
developing PWMLs [11,13]. Further, it is also possible that cardiac
anomalies in some patients with SLC13A5 related DEE could contribute
to ischemic injury [10].
In addition to PWMLs, other white matter abnormalities were also
observed in the literature such as delayed myelination [22]. Citrate
plays an important role in fatty acid synthesis, so its deficiency could
impair myelination in patients with SLC13A5 related DEE [10,11].
Delayed myelination in previously reported cases either occurred alone,
or following the appearance of PWMLs [11,22]. A number of other
non-specific abnormalities were observed in the literature, as shown in
Table 1. Of importance, frontal lobe thickening and a FCD were
observed in two cases, which may have important treatment implica­
tions (i.e., possible resection) if these areas are responsible for refractory
seizures [14,22]. The link between SLC13A5 related DEE and focal
cortical malformations, however, has not been well described before.
Limitations to our study include that not all cases with SLC13A5
related DEE had neuroimaging data available (i.e.., 40% were missing).
It is therefore possible that other types of brain imaging abnormalities
could be missed or under called as a result. Further, although initial MRI
was often done, follow up MRI was seldom completed. Thus, the lon­
gitudinal spectrum of neuroimaging findings in SLC13A5 related DEE is
not fully known. Future studies are therefore needed to better under­
stand the extent and progression of neuroimaging features in SLC13A5
related DEE and their impact on neurodevelopmental outcomes (if any).
Additional studies are also needed to better explore the potential asso­
ciation between PWMLs and SLC13A5 related DEE, given that these
lesions may be caused by a wide number of aetiologies. In addition,
future research is needed to determine why certain patients with
SLC13A5 related DEE are particularly susceptive with white matter le­
sions such as PWMLs. It will also be of interest to determine whether the
genotype and phenotype differs between those that have PWMLs and
those that do not in larger cohorts of SLC13A5 related DEE.

Table 2
Variants in the SLC13A5 gene in our reported case.
Variant:

ACMG Criteria [17]

Inheritance/
Novel or
Previously
Reported

Classification

SLC13A5,
NM_177550.4:
c.655G>A, p.
Gly219Arg

2 strong: P3 þ PS4
PS3 – well-established in
vitro or in vivo functional
studies supportive of a
damaging effect on the
gene or gene product
(Hardies et al., 2015)
PS4-The presence of the
variant in affected
individuals is significant
increased compared with
prevalence in controls (i.
e., multiple studies show
multiple unrelated
individuals with same
variant [12–14,22]
3 moderate PM2, PM3,
PM5
PM2 - absent from
controls or at extremely
low frequency if recessive
(allele frequent gnomAD
0.00007959)
PM3 - for recessive
disorders, detected in
trans with a pathogenic
variant (as above)
PM5 - Novel missense
change at amino acid
residue where a different
missense change
determined to be
pathogenic has been seen
before (i.e., p.Pro68Gln –
[21])
Additional:
PP3 – multiple lines of
evidence suggest
deleterious effect:
Mutation taster, SIFT,
polyphen-2 all
damaging/deleterious
Proline is highly
conserved and moderate
physiochemical difference
with serine

Inherited
(Maternal)
Previously
reported

Pathogenic

Inherited
(Paternal)
Novel

Likely
pathogenic

SLC13A5,
NM_177550.4:
c.202C>T, p.
Pro68Ser

and include non-specific hyperintensities, PWMLs, delayed myelination,
and PVL. PWMLs are the most common white matter abnormality
observed in patients with SLC13A5 related DEE to date. PWMLs are
small patches of increased signal intensity on T1 imaging, and decreased
intensity on T2 imaging [11,27]. Moreover, they show diffusion re­
striction with increased signal on diffusion weighted imaging (DWI) and
corresponding dark signal on apparent diffusion coefficient (ADC) map
[11,27]. PWMLs are thought to be ischemic in origin and relate to injury
of the oligodendrocyte progenitor cells and subplate neurons [11,27].
Typically, PWMLs may be observed in very preterm infants (20–50%),
but they may also be observed in term infants, for example in the setting
of hypoxic ischemic encephalopathy, infection (i.e., parechovirus,
cytomegalovirus), congenital heart disease, genetic or metabolic disor­
ders (i.e., hypoglycemia, mitochondrial disorders, methylmalonic acid­
emia and other inborn errors of metabolism) [11,27]. Therefore, it is
important that a broad differential for PWMLs is considered when
approaching a child with new onset seizures and/or other neurological
findings.
The etiology of PWMLs is important, and genetic causes may be
associated with poorer prognosis or higher lesion number [11]. Location
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5. Conclusion

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In conclusion, we present an additional case of SLC13A5 related DEE
and provide insight into the neuroimaging phenotype of this condition.
While two thirds of MRIs are normal in this condition, up to one third
can have abnormalities, predominantly in the white matter [5,9,11,
13–15,19–23]. PWMLs appear to be the most common white matter
abnormality observed and are typically seen at presentation in infancy
and may have an extensive topographic distribution [11,13]. The eti­
ology of PWMLs remains unknown but may be related to central nervous
system energy failure, predisposition to ischemia, or other unknown
factors [9–11]. Presently, it remains unknown why some patients with
SLC13A5 related DEE are susceptible to such lesions and how these le­
sions impact neurodevelopmental outcomes. Overall, further research is
needed to better understand the potential association between PWMLs
and SLC13A5 related DEE.
Declaration of Competing Interest
None.
Acknowledgments
We thank the patient and their caregivers for participating in this
study.
Funding
None.
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