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| Likely inborn error of metabolism v9.38 | SLC2A1 |
Ida Ertmanska changed review comment from: PMID: 41561681 Previtali et al., 2026 - MONOALLELIC COHORT Retrospective evaluation of 32 adults with genetically confirmed GLUT1DS from Italian medical centres. 17/32 variants in SLC2A1 were confirmed to be de novo, 10 inherited from a parent, and 5 of unknown inheritance. 24/32 patients had epilepsy, 26 had paroxysmal movement disorders. Fatigue was present in 12 individuals and migraine in 6. Psychomotor delay was observed in 15/32 subjects. Subsequently, 11/32 individuals received a diagnosis of intellectual disability. Mean age at symptom onset was 4 yrs. Brain MRI was unremarkable in most cases (15/20). Mostly missense variants detected. Study highlights that "GLUT1DS presents with variable symptoms, often unrecognised or too mild to prompt clinical attention." Several adults in the study were diagnosed in adulthood - some asymptomatic and only following their child’s diagnosis. BIALLELIC CASES: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026).; to: PMID: 41561681 Previtali et al., 2026 Retrospective evaluation of 32 adults with genetically confirmed GLUT1DS from Italian medical centres. 17/32 variants in SLC2A1 were confirmed to be de novo, 10 inherited from a parent, and 5 of unknown inheritance. 24/32 patients had epilepsy, 26 had paroxysmal movement disorders. Fatigue was present in 12 individuals and migraine in 6. Psychomotor delay was observed in 15/32 subjects. Subsequently, 11/32 individuals received a diagnosis of intellectual disability. Mean age at symptom onset was 4 yrs. Brain MRI was unremarkable in most cases (15/20). Mostly missense variants detected. Study highlights that "GLUT1DS presents with variable symptoms, often unrecognised or too mild to prompt clinical attention." Several adults in the study were diagnosed in adulthood - some asymptomatic and only following their child’s diagnosis. PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026). |
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| Likely inborn error of metabolism v9.37 | SLC2A1 | Ida Ertmanska Phenotypes for gene: SLC2A1 were changed from Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126 to GLUT1 deficiency syndrome 2, childhood onset, OMIM:612126; childhood onset GLUT1 deficiency syndrome 2, MONDO:0012805; GLUT1 deficiency syndrome 1, infantile onset, severe, OMIM:606777; encephalopathy due to GLUT1 deficiency, MONDO:0011724; Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.36 | SLC2A1 | Ida Ertmanska Publications for gene: SLC2A1 were set to 27604308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska Tag Q4_26_MOI tag was added to gene: SLC2A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are numerous patients reported in literature with monoallelic SLC2A1 variants and GLUT1 deficiency syndrome (characterised by early-onset epileptic encephalopathy associated with hypoglycorrhachia, delayed development, acquired microcephaly, motor incoordination, and spasticity). There are only two probands reported to date with biallelic SLC2A1 variants and GLUT1 deficiency syndrome. While their heterozygous family members were reported as asymptomatic, GLUT1DS presents with variable and often mild symptoms. Hence, the mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted on this panel.; to: Comment on mode of inheritance: There are numerous patients reported in literature with monoallelic SLC2A1 variants and GLUT1 deficiency syndrome (characterised by early-onset epileptic encephalopathy associated with hypoglycorrhachia, delayed development, acquired microcephaly, motor incoordination, and spasticity). There are only two probands reported to date with biallelic SLC2A1 variants and GLUT1 deficiency syndrome. While their heterozygous family members were reported as asymptomatic, GLUT1DS presents with variable and often mild symptoms. Hence, the mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted on this panel, until more biallelic cases are reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are numerous patients reported in literature with monoallelic SLC2A1 variants and GLUT1 deficiency syndrome (characterised by early-onset epileptic encephalopathy associated with hypoglycorrhachia, delayed development, acquired microcephaly, motor incoordination, and spasticity). There are only two probands reported to date with biallelic SLC2A1 variants and GLUT1 deficiency syndrome. Hence, the mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted on this panel.; to: Comment on mode of inheritance: There are numerous patients reported in literature with monoallelic SLC2A1 variants and GLUT1 deficiency syndrome (characterised by early-onset epileptic encephalopathy associated with hypoglycorrhachia, delayed development, acquired microcephaly, motor incoordination, and spasticity). There are only two probands reported to date with biallelic SLC2A1 variants and GLUT1 deficiency syndrome. While their heterozygous family members were reported as asymptomatic, GLUT1DS presents with variable and often mild symptoms. Hence, the mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 |
Ida Ertmanska changed review comment from: PMID: 41561681 Previtali et al., 2026 - MONOALLELIC COHORT Retrospective evaluation of 32 adults with genetically confirmed GLUT1DS from Italian medical centres. 17/32 variants in SLC2A1 were confirmed to be de novo, 10 inherited from a parent, and 5 of unknown inheritance. 24/32 patients had epilepsy, 26 had paroxysmal movement disorders. Fatigue was present in 12 individuals and migraine in 6. Psychomotor delay was observed in 15/32 subjects. Subsequently, 11/32 individuals received a diagnosis of intellectual disability. Mean age at symptom onset was 4 yrs. Brain MRI was unremarkable in most cases (15/20). Mostly missense variants detected. BIALLELIC CASES: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026).; to: PMID: 41561681 Previtali et al., 2026 - MONOALLELIC COHORT Retrospective evaluation of 32 adults with genetically confirmed GLUT1DS from Italian medical centres. 17/32 variants in SLC2A1 were confirmed to be de novo, 10 inherited from a parent, and 5 of unknown inheritance. 24/32 patients had epilepsy, 26 had paroxysmal movement disorders. Fatigue was present in 12 individuals and migraine in 6. Psychomotor delay was observed in 15/32 subjects. Subsequently, 11/32 individuals received a diagnosis of intellectual disability. Mean age at symptom onset was 4 yrs. Brain MRI was unremarkable in most cases (15/20). Mostly missense variants detected. Study highlights that "GLUT1DS presents with variable symptoms, often unrecognised or too mild to prompt clinical attention." Several adults in the study were diagnosed in adulthood - some asymptomatic and only following their child’s diagnosis. BIALLELIC CASES: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026). |
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| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska edited their review of gene: SLC2A1: Changed publications to: 10980529, 20221955, 20687207, 41561681 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 |
Ida Ertmanska changed review comment from: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026).; to: PMID: 41561681 Previtali et al., 2026 - MONOALLELIC COHORT Retrospective evaluation of 32 adults with genetically confirmed GLUT1DS from Italian medical centres. 17/32 variants in SLC2A1 were confirmed to be de novo, 10 inherited from a parent, and 5 of unknown inheritance. 24/32 patients had epilepsy, 26 had paroxysmal movement disorders. Fatigue was present in 12 individuals and migraine in 6. Psychomotor delay was observed in 15/32 subjects. Subsequently, 11/32 individuals received a diagnosis of intellectual disability. Mean age at symptom onset was 4 yrs. Brain MRI was unremarkable in most cases (15/20). Mostly missense variants detected. BIALLELIC CASES: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026). |
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| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska commented on gene: SLC2A1: Comment on mode of inheritance: There are numerous patients reported in literature with monoallelic SLC2A1 variants and GLUT1 deficiency syndrome (characterised by early-onset epileptic encephalopathy associated with hypoglycorrhachia, delayed development, acquired microcephaly, motor incoordination, and spasticity). There are only two probands reported to date with biallelic SLC2A1 variants and GLUT1 deficiency syndrome. Hence, the mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.35 | SLC2A1 |
Ida Ertmanska changed review comment from: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026).; to: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). Variants R126L (SLC2A1 c.377G>T (p.Arg126Leu)) & K256V (SLC2A1: c.766_767delinsGT (p.Lys256Val)) are not reported in gnomAD v4.1.2. SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026). |
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| Likely inborn error of metabolism v9.35 | SLC2A1 |
Ida Ertmanska changed review comment from: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (R126L inherited from an asymptomatic mother). SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026).; to: PMID: 20687207 Rotstein et al., 2011 F1 - male proband seen at 3 yrs, with seizures, dev delay, progressive postnatal microcephaly, hypoglycorrhachia on CSF analysis. He had spasticity with distant lower limb dystonia. Parents and sister unaffected. He was found to carry comp het SLC2A1 (old name GLUT1) variants: c.945A>G, p.K256V (maternally inherited) and c.556G>T, p.R126L (de novo). Looks to be the same patient as P13 in PMID: 10980529. F2 - two affectes sisters, aged 6 and 2.5 yrs. Seems to be the same family as in PMID: 20221955. Only SLC2A1 was analysed, method not described. PMID: 20221955 Klepper et al., 2009 Report of a 6yo female patient from a consanguineous Arab family from Qatar, with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Symptom onset was around 18 months of age, with frequent falls and an ataxic gait. She harboured a homozygous SLC2A1: c.1402C>T (p.Arg468Trp) variant - also homozygous in her younger sister who was asymptomatic. Unaffected parents were het for the variant. 3 hets reported in gnomAD v4.1.2, no hmz. Method: targeted sequencing of SLC2A1. PMID: 10980529 Wang et al., 2000 Report of 15 children with infantile seizures, acquired microcephaly, low CSF/blood glucose ratio, and dev delay, harbouring SLC2A1 variants. Method: PCR sequencing of SLC2A1 only. 7 patients had het nonsense variants in SLC2A1, 3 had splicing variants, and 1 harboured a large deletion. 4 patients had missense variants, including Patient 13 with comp het SLC2A1 variants R126L and K256V (K256V inherited from an asymptomatic mother). SLC2A1 association with AD GLUT1 deficiency syndrome is classified as Definitive in ClinGen (Intellectual Disability and Autism GCEP, Apr 2019). The gene is associated with several disease entities in OMIM: AD {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM:614847; AD Dystonia 9, MIM:601042; AD GLUT1 deficiency syndrome 2, childhood onset, MIM:612126; AD, AR GLUT1 deficiency syndrome 1, infantile onset, severe, MIM:606777; AD Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 (accessed 7th Oct 2026). |
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| Likely inborn error of metabolism v9.35 | SLC2A1 | Ida Ertmanska reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10980529, 20221955, 20687207; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, OMIM:606777, encephalopathy due to GLUT1 deficiency, MONDO:0011724; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.331 | SLC2A1 | Ivone Leong Classified gene: SLC2A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.331 | SLC2A1 |
Ivone Leong Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. SLC2A1 is associated with GLUT1 deficiency syndrome 1 and GLUT1 deficiency syndrome 2 on OMIM and Gene2Phenotype. There are >3 unrelated cases reported on OMIM. Therefore, there is enough evidence for this gene to be promoted to Green status. |
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| Likely inborn error of metabolism v1.331 | SLC2A1 | Ivone Leong Gene: slc2a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.278 | SLC2A1 | Ivone Leong Phenotypes for gene: SLC2A1 were changed from Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.47 | SLC2A1 |
Ivone Leong Source NHS GMS was added to SLC2A1. Source London North GLH was added to SLC2A1. |
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| Likely inborn error of metabolism v0.4 | SLC2A1 |
Ellen McDonagh gene: SLC2A1 was added gene: SLC2A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SLC2A1 were set to 27604308 Phenotypes for gene: SLC2A1 were set to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies |
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