SLC45A1-Related Neuronal Glucose Transporter Deficiency

Mendelian MONDO:0044322 Pathograph 4 Show in embeddings browser Neurodevelopmental Disorder Intellectual Disability

SLC45A1-related neuronal glucose transporter deficiency is an ultra-rare autosomal recessive neurodevelopmental disorder caused by biallelic loss-of-function variants in SLC45A1, which encodes the second known cerebral glucose transporter (after GLUT1/SLC2A1). Reported individuals present with moderate to severe intellectual disability, epilepsy (including focal-onset seizures), and variable neuropsychiatric features such as anxiety and autistic behaviors, with mild facial dysmorphism in some. Only a handful of families have been reported to date.

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1
Inheritance
2
Pathophys.
4
Phenotypes
4
Pathograph
1
Genes
2
Medical Actions
👪

Inheritance

1
Autosomal recessive HP:0000007
All reported affected individuals carry biallelic (homozygous or compound heterozygous) SLC45A1 variants segregating with the phenotype in consanguineous or non-consanguineous families.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:28434495 SUPPORT Human Clinical
"glucose transporter, in two consanguineous multiplex families with moderate to severe ID, epilepsy, and variable neuropsychiatric features. The variants segregate with the phenotype in these families"
Establishes biallelic (homozygous) SLC45A1 variants segregating with disease in consanguineous multiplex families.
PMID:40541196 SUPPORT Human Clinical
"Exome analysis revealed compound heterozygous variants p.Pro560Leu and p.Arg57Cys in the SLC45A1 gene."
A fifth, unrelated patient also carries biallelic (compound heterozygous) SLC45A1 variants, reinforcing autosomal recessive inheritance.
⚙

Pathophysiology

2
SLC45A1 Loss of Function
Biallelic SLC45A1 variants reduce the glucose transport activity of the encoded protein, a cerebral glucose transporter expressed in the developing and adult brain (cortex and cerebellum). Missense variants tested in transfected COS-7/COS7 cells show substantially reduced intracellular glucose transport activity relative to wild-type SLC45A1, in one case attributable to failure of the mutant protein to localize correctly to the cytomembrane.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
SLC45A1 hgnc:17939 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SLC45A1 (hgnc:17939). hgnc:17939 is a gene from the HUGO Gene Nomenclature Committee.
D-glucose transmembrane transport GO:1904659 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased D-glucose transmembrane transport (GO:1904659). GO:1904659 is a biological process from the Gene Ontology. ↓ DECREASED
D-glucose transmembrane transporter activity GO:0055056 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased D-glucose transmembrane transporter activity (GO:0055056). GO:0055056 is a molecular function from the Gene Ontology. ↓ DECREASED
brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Impaired Neuronal Glucose Transport Reduced SLC45A1 glucose transport activity is proposed to impair glucose uptake into neural cells, analogous to the mechanism of GLUT1 (SLC2A1) deficiency, the only other known cerebral glucose transporter disorder.
Show evidence (2 references)
PMID:28434495 SUPPORT In Vitro
"glucose transport activity of the p.Arg176Trp and p.Ala210Val SLC45A1 variants, measured in transfected COS-7 cells, was approximately 50% (p = 0.013) and 33% (p = 0.008) lower, respectively, than that of intact SLC45A1."
Direct functional evidence that disease-associated SLC45A1 missense variants reduce glucose transport activity in a cell-based assay.
PMID:39003656 SUPPORT In Vitro
"In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th amino acid were changed, location on the cytomembrane was failed, their activity to transport glucose was also significantly decreased to contrast with SLC45A1-WT."
Independent functional replication showing mutant SLC45A1 mislocalizes and has attenuated glucose transport activity relative to wild-type.
Impaired Neuronal Glucose Transport
Impaired glucose transport into neural cells is the proposed proximate mechanism linking SLC45A1 dysfunction to the neurodevelopmental phenotype, though (unlike GLUT1 deficiency) CSF glucose has not been reported as reduced in the published SLC45A1 cases.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
SLC45A1 hgnc:17939 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SLC45A1 (hgnc:17939). hgnc:17939 is a gene from the HUGO Gene Nomenclature Committee.
D-glucose transmembrane transport GO:1904659 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased D-glucose transmembrane transport (GO:1904659). GO:1904659 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Neurodevelopmental and Epileptic Phenotype Impaired neuronal glucose transport is hypothesized to underlie the combination of intellectual disability, epilepsy, and neuropsychiatric features seen in affected individuals, and is consistent with the response of seizures to ketogenic diet (which provides an alternative, transporter-independent brain fuel source) reported in one patient.
Show evidence (1 reference)
PMID:40541196 SUPPORT Human Clinical
"Solute carrier family 45 member A1 (SLC45A1) is a glucose brain transporter predominantly expressed in the developing and adult brain, including the cortex and cerebellum."
Confirms SLC45A1 as a brain-expressed glucose transporter, supporting the proposed neuronal glucose transport deficit.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Referential integrity issues (1):
  • Target 'Neurodevelopmental and Epileptic Phenotype' (from 'Impaired Neuronal Glucose Transport') not found in named elements
Pathograph: causal mechanism network for SLC45A1-Related Neuronal Glucose Transporter Deficiency Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

4
Intellectual Disability Clinical HP:0001249 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Moderate to severe intellectual disability, annotated with Intellectual disability (HP:0001249). HP:0001249 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28434495 SUPPORT Human Clinical
"glucose transporter, in two consanguineous multiplex families with moderate to severe ID, epilepsy, and variable neuropsychiatric features."
Directly reports moderate to severe intellectual disability in the two founding families.
Seizures Clinical HP:0007359 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Focal-onset seizure (HP:0007359). HP:0007359 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40541196 SUPPORT Human Clinical
"Long-term video electroencephalogram and semiology were evocative of a left-frontal focus."
Confirms a focal-onset seizure semiology in the reported SLC45A1 patient.
PMID:28434495 SUPPORT Human Clinical
"All together, our data strongly suggest that recessive mutations in SLC45A1 cause ID and epilepsy."
The founding genetic paper concludes that biallelic SLC45A1 variants cause epilepsy in addition to intellectual disability.
Neuropsychiatric Features Clinical HP:0000739 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anxiety (HP:0000739). HP:0000739 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28434495 SUPPORT Human Clinical
"in two consanguineous multiplex families with moderate to severe ID, epilepsy, and variable neuropsychiatric features."
The disease paper reports variable neuropsychiatric features in affected individuals; the specific anxiety/OCD/autistic-feature detail is summarized in the MONDO/OMIM definition citing this same study.
Developmental Delay Clinical HP:0001263 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Global developmental delay (HP:0001263). HP:0001263 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40541196 SUPPORT Human Clinical
"A 3-year-old boy presented with developmental delay and unexpected nighttime arousals followed by sudden right arm extension suggestive of epilepsy."
Directly documents developmental delay as a presenting feature in the fifth reported SLC45A1 patient.
🧬

Genetic Associations

1
SLC45A1 biallelic loss-of-function/hypomorphic variants (Causative)
Gene: SLC45A1 hgnc:17939 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SLC45A1 (hgnc:17939). hgnc:17939 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (3 references)
PMID:28434495 SUPPORT Human Clinical
"The variants segregate with the phenotype in these families, affect well-conserved amino acids, and are predicted to be damaging by in silico programs."
Establishes segregation of the SLC45A1 variants with disease in the founding families.
PMID:39003656 SUPPORT Human Clinical
"Through trio-based exome sequencing, the missense mutations of SLC45A1 c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the proband with syndromic ID."
Independent trio exome sequencing identifies compound heterozygous SLC45A1 missense variants in a proband with syndromic intellectual disability.
PMID:40541196 SUPPORT Human Clinical
"Pathogenic variants in SLC45A1 have been described in four patients from two unrelated families with dysmorphic features, intellectual disability, and focal epilepsy. We describe the fifth SLC45A1 patient"
Confirms the small total number of reported SLC45A1 patients and adds a fifth case with compound heterozygous variants.
💊

Medical Actions

2
Ketogenic Diet
Action: ketogenic diet intakeNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is ketogenic diet intake, annotated with Ketogenic Diet (NCIT:C173168). NCIT:C173168 is a clinical intervention from the NCI Thesaurus. Ontology label: Ketogenic Diet NCIT:C173168
A ketogenic diet was used in one reported patient with SLC45A1-related focal refractory epilepsy and produced seizure freedom with cognitive improvement; seizures relapsed after the diet was stopped.
Show evidence (1 reference)
PMID:40541196 SUPPORT Human Clinical
"Meanwhile, a KD was introduced, and the child became seizure-free with cognitive improvement. After 2 years, the KD was stopped, and seizures relapsed."
Directly documents ketogenic diet efficacy (seizure freedom) and relapse on discontinuation in a genetically confirmed SLC45A1 patient.
Acetazolamide
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: acetazolamide CHEBI:27690 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses acetazolamide (CHEBI:27690). CHEBI:27690 is a therapeutic agent from Chemical Entities of Biological Interest.
Acetazolamide was introduced after ketogenic-diet relapse in one reported patient and achieved seizure freedom for 10 months.
Show evidence (1 reference)
PMID:40541196 SUPPORT Human Clinical
"Acetazolamide was introduced with seizure freedom for 10 months."
Directly documents acetazolamide efficacy after ketogenic-diet relapse in a genetically confirmed SLC45A1 patient.
{ }

Source YAML

click to show 
name: SLC45A1-Related Neuronal Glucose Transporter Deficiency
creation_date: "2026-07-06T00:00:00Z"
category: Mendelian
synonyms:
- Intellectual developmental disorder with neuropsychiatric features
- IDDNPF
- SLC45A1-related intellectual disability and epilepsy
description: >-
  SLC45A1-related neuronal glucose transporter deficiency is an ultra-rare
  autosomal recessive neurodevelopmental disorder caused by biallelic
  loss-of-function variants in SLC45A1, which encodes the second known
  cerebral glucose transporter (after GLUT1/SLC2A1). Reported individuals
  present with moderate to severe intellectual disability, epilepsy
  (including focal-onset seizures), and variable neuropsychiatric features
  such as anxiety and autistic behaviors, with mild facial dysmorphism in
  some. Only a handful of families have been reported to date.
disease_term:
  preferred_term: intellectual developmental disorder with neuropsychiatric features
  term:
    id: MONDO:0044322
    label: intellectual developmental disorder with neuropsychiatric features
parents:
- Neurodevelopmental Disorder
- Intellectual Disability
notes: >-
  MONDO:0044322 cross-references OMIM:617532 and carries a direct
  gene-disease relationship (RO:0004003) to SLC45A1 (hgnc:17939), confirming
  the seed OMIM id and ruling out named-entity confusion with GLUT1
  deficiency syndrome (SLC2A1) or other SLC-transporter disorders. Orphanet
  ORPHA:88616 was checked as a seed identifier but as of this curation the
  Orphadata cache under references_cache/ has no ORPHA_88616.md entry; the
  primary literature anchor used here is the MONDO/OMIM record above. Only
  three usable primary/case reports were identified in PubMed as of
  2026-07-06 (Srour et al. 2017, PMID:28434495; Zhou et al. 2024,
  PMID:39003656; Semal et al. 2025, PMID:40541196), consistent with this
  being an ultra-rare, recently described gene-disease association.
inheritance:
- name: Autosomal recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    All reported affected individuals carry biallelic (homozygous or compound
    heterozygous) SLC45A1 variants segregating with the phenotype in
    consanguineous or non-consanguineous families.
  evidence:
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      glucose transporter, in two consanguineous multiplex families with
      moderate to severe ID, epilepsy, and variable neuropsychiatric
      features. The variants segregate with the phenotype in these families
    explanation: >-
      Establishes biallelic (homozygous) SLC45A1 variants segregating with
      disease in consanguineous multiplex families.
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Exome analysis revealed compound heterozygous variants p.Pro560Leu and
      p.Arg57Cys in the SLC45A1 gene.
    explanation: >-
      A fifth, unrelated patient also carries biallelic (compound
      heterozygous) SLC45A1 variants, reinforcing autosomal recessive
      inheritance.
pathophysiology:
- name: SLC45A1 Loss of Function
  description: >-
    Biallelic SLC45A1 variants reduce the glucose transport activity of the
    encoded protein, a cerebral glucose transporter expressed in the
    developing and adult brain (cortex and cerebellum). Missense variants
    tested in transfected COS-7/COS7 cells show substantially reduced
    intracellular glucose transport activity relative to wild-type SLC45A1,
    in one case attributable to failure of the mutant protein to localize
    correctly to the cytomembrane.
  genes:
  - preferred_term: SLC45A1
    term:
      id: hgnc:17939
      label: SLC45A1
  molecular_functions:
  - preferred_term: D-glucose transmembrane transporter activity
    term:
      id: GO:0055056
      label: D-glucose transmembrane transporter activity
    modifier: DECREASED
  biological_processes:
  - preferred_term: D-glucose transmembrane transport
    term:
      id: GO:1904659
      label: D-glucose transmembrane transport
    modifier: DECREASED
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  chemical_entities:
  - preferred_term: glucose
    term:
      id: CHEBI:17234
      label: glucose
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      glucose transport activity of the p.Arg176Trp and p.Ala210Val SLC45A1
      variants, measured in transfected COS-7 cells, was approximately 50%
      (p = 0.013) and 33% (p = 0.008) lower, respectively, than that of
      intact SLC45A1.
    explanation: >-
      Direct functional evidence that disease-associated SLC45A1 missense
      variants reduce glucose transport activity in a cell-based assay.
  - reference: PMID:39003656
    reference_title: Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th
      amino acid were changed, location on the cytomembrane was failed, their
      activity to transport glucose was also significantly decreased to
      contrast with SLC45A1-WT.
    explanation: >-
      Independent functional replication showing mutant SLC45A1 mislocalizes
      and has attenuated glucose transport activity relative to wild-type.
  downstream:
  - target: Impaired Neuronal Glucose Transport
    description: >-
      Reduced SLC45A1 glucose transport activity is proposed to impair
      glucose uptake into neural cells, analogous to the mechanism of GLUT1
      (SLC2A1) deficiency, the only other known cerebral glucose transporter
      disorder.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28434495
      reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Glucose transport across the blood brain barrier and into neural
        cells is critical for normal cerebral physiologic function.
        Dysfunction of the cerebral glucose transporter GLUT1 (encoded by
        SLC2A1) is known to result in epilepsy, intellectual disability (ID),
        and movement disorder.
      explanation: >-
        The paper frames SLC45A1 as a second cerebral glucose transporter
        whose dysfunction is mechanistically analogous to GLUT1 deficiency,
        which is caused by impaired neuronal glucose uptake.
- name: Impaired Neuronal Glucose Transport
  description: >-
    Impaired glucose transport into neural cells is the proposed proximate
    mechanism linking SLC45A1 dysfunction to the neurodevelopmental
    phenotype, though (unlike GLUT1 deficiency) CSF glucose has not been
    reported as reduced in the published SLC45A1 cases.
  genes:
  - preferred_term: SLC45A1
    term:
      id: hgnc:17939
      label: SLC45A1
  biological_processes:
  - preferred_term: D-glucose transmembrane transport
    term:
      id: GO:1904659
      label: D-glucose transmembrane transport
    modifier: DECREASED
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  evidence:
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Solute carrier family 45 member A1 (SLC45A1) is a glucose brain
      transporter predominantly expressed in the developing and adult brain,
      including the cortex and cerebellum.
    explanation: >-
      Confirms SLC45A1 as a brain-expressed glucose transporter, supporting
      the proposed neuronal glucose transport deficit.
  downstream:
  - target: Neurodevelopmental and Epileptic Phenotype
    description: >-
      Impaired neuronal glucose transport is hypothesized to underlie the
      combination of intellectual disability, epilepsy, and neuropsychiatric
      features seen in affected individuals, and is consistent with the
      response of seizures to ketogenic diet (which provides an alternative,
      transporter-independent brain fuel source) reported in one patient.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40541196
      reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Meanwhile, a KD was introduced, and the child became seizure-free
        with cognitive improvement.
      explanation: >-
        Clinical response to ketogenic diet (an alternative brain-fuel
        strategy used in other cerebral-glucose-transport disorders such as
        GLUT1 deficiency) is consistent with an underlying neuronal glucose
        transport deficit, though the paper does not directly measure CSF
        glucose in this patient.
phenotypes:
- category: Clinical
  name: Intellectual Disability
  description: >-
    Moderate to severe intellectual disability is reported in all described
    families.
  phenotype_term:
    preferred_term: Moderate to severe intellectual disability
    term:
      id: HP:0001249
      label: Intellectual disability
  evidence:
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      glucose transporter, in two consanguineous multiplex families with
      moderate to severe ID, epilepsy, and variable neuropsychiatric
      features.
    explanation: >-
      Directly reports moderate to severe intellectual disability in the two
      founding families.
- category: Clinical
  name: Seizures
  description: >-
    Epilepsy, including focal-onset seizures, is reported in affected
    individuals and can be refractory to standard anticonvulsants.
  phenotype_term:
    preferred_term: Focal-onset seizure
    term:
      id: HP:0007359
      label: Focal-onset seizure
  evidence:
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Long-term video electroencephalogram and semiology were evocative of a
      left-frontal focus.
    explanation: >-
      Confirms a focal-onset seizure semiology in the reported SLC45A1
      patient.
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All together, our data strongly suggest that recessive mutations in
      SLC45A1 cause ID and epilepsy.
    explanation: >-
      The founding genetic paper concludes that biallelic SLC45A1 variants
      cause epilepsy in addition to intellectual disability.
- category: Clinical
  name: Neuropsychiatric Features
  description: >-
    Variable neuropsychiatric abnormalities, such as anxiety,
    obsessive-compulsive behavior, and autistic features, are described as
    part of the phenotype (per the MONDO/OMIM disease definition
    summarizing Srour et al. 2017).
  phenotype_term:
    preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      in two consanguineous multiplex families with moderate to severe ID,
      epilepsy, and variable neuropsychiatric features.
    explanation: >-
      The disease paper reports variable neuropsychiatric features in
      affected individuals; the specific anxiety/OCD/autistic-feature detail
      is summarized in the MONDO/OMIM definition citing this same study.
- category: Clinical
  name: Developmental Delay
  description: >-
    Developmental delay is reported as an early presenting feature.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A 3-year-old boy presented with developmental delay and unexpected
      nighttime arousals followed by sudden right arm extension suggestive
      of epilepsy.
    explanation: >-
      Directly documents developmental delay as a presenting feature in the
      fifth reported SLC45A1 patient.
genetic:
- name: SLC45A1 biallelic loss-of-function/hypomorphic variants
  association: Causative
  relationship_type: CAUSATIVE
  gene_term:
    preferred_term: SLC45A1
    term:
      id: hgnc:17939
      label: SLC45A1
  variant_origin: GERMLINE
  notes: >-
    As of this curation (2026-07-06), only five affected individuals across
    three families have been reported in the literature (two consanguineous
    families in Srour et al. 2017, one family in Zhou et al. 2024, and one
    sporadic patient in Semal et al. 2025).
  evidence:
  - reference: PMID:28434495
    reference_title: Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The variants segregate with the phenotype in these families, affect
      well-conserved amino acids, and are predicted to be damaging by in
      silico programs.
    explanation: >-
      Establishes segregation of the SLC45A1 variants with disease in the
      founding families.
  - reference: PMID:39003656
    reference_title: Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Through trio-based exome sequencing, the missense mutations of SLC45A1
      c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the
      proband with syndromic ID.
    explanation: >-
      Independent trio exome sequencing identifies compound heterozygous
      SLC45A1 missense variants in a proband with syndromic intellectual
      disability.
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pathogenic variants in SLC45A1 have been described in four patients
      from two unrelated families with dysmorphic features, intellectual
      disability, and focal epilepsy. We describe the fifth SLC45A1 patient
    explanation: >-
      Confirms the small total number of reported SLC45A1 patients and adds
      a fifth case with compound heterozygous variants.
treatments:
- name: Ketogenic Diet
  description: >-
    A ketogenic diet was used in one reported patient with SLC45A1-related
    focal refractory epilepsy and produced seizure freedom with cognitive
    improvement; seizures relapsed after the diet was stopped.
  treatment_term:
    preferred_term: ketogenic diet intake
    term:
      id: NCIT:C173168
      label: Ketogenic Diet
  evidence:
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Meanwhile, a KD was introduced, and the child became seizure-free
      with cognitive improvement. After 2 years, the KD was stopped, and
      seizures relapsed.
    explanation: >-
      Directly documents ketogenic diet efficacy (seizure freedom) and
      relapse on discontinuation in a genetically confirmed SLC45A1 patient.
- name: Acetazolamide
  description: >-
    Acetazolamide was introduced after ketogenic-diet relapse in one
    reported patient and achieved seizure freedom for 10 months.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: acetazolamide
      term:
        id: CHEBI:27690
        label: acetazolamide
  evidence:
  - reference: PMID:40541196
    reference_title: "Solute Carrier 45A1: A New Cerebral Glucose Transporter Brain Disorder with Focal Refractory Epilepsy Responsive to Ketogenic Diet and Acetazolamide."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acetazolamide was introduced with seizure freedom for 10 months.
    explanation: >-
      Directly documents acetazolamide efficacy after ketogenic-diet relapse
      in a genetically confirmed SLC45A1 patient.