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GLUT1 deficiency syndrome

MedGen UID:
337833
Concept ID:
C1847501
Disease or Syndrome
Synonyms: Glucose transporter type 1 deficiency syndrome; GLUT-1 deficiency syndrome; GLUT1 DS
 
Related gene: SLC2A1
 
Monarch Initiative: MONDO:0000188
OMIM®: 606777
OMIM® Phenotypic series: PS606777

Disease characteristics

Excerpted from the GeneReview: Glucose Transporter Type 1 Deficiency Syndrome
Glucose transporter type 1 deficiency syndrome (Glut1DS) is a disorder of brain energy metabolism. Glucose, the essential metabolic fuel for the brain, is transported into the brain exclusively by the protein glucose transporter type 1 (Glut1) across the endothelial cells forming the blood-brain barrier (BBB). Glut1DS results from the inability of Glut1 to transfer sufficient glucose across the BBB to meet the glucose demands of the brain. The needs of the brain for glucose increase rapidly after birth, peaking in early childhood, remaining high until about age 10 years, then gradually decreasing throughout adolescence and plateauing in early adulthood. When first diagnosed in infancy to early childhood, the predominant clinical findings of Glut1DS are paroxysmal eye-head movements, pharmacoresistant seizures of varying types, deceleration of head growth, and developmental delay. Subsequently children develop complex movement disorders and intellectual disability ranging from mild to severe. Institution of ketogenic diet therapies (KDTs) helps with early neurologic growth and development and seizure control. Typically, the earlier the treatment the better the long-term clinical outcome. When first diagnosed in later childhood to adulthood (occasionally in a parent following the diagnosis of an affected child), the predominant clinical findings of Glut1DS are usually complex paroxysmal movement disorders, spasticity, ataxia, dystonia, speech difficulty, and intellectual disability. [from GeneReviews]
Authors:
Dong Wang  |  Tristan Sands  |  Maoxue Tang, et. al.   view full author information

Additional description

From MedlinePlus Genetics
GLUT1 deficiency syndrome is a disorder affecting the nervous system that can have a variety of neurological signs and symptoms. Approximately 90 percent of affected individuals have a form of the disorder often referred to as common GLUT1 deficiency syndrome. These individuals generally have frequent seizures (epilepsy) beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have a normal head size at birth, but growth of the brain and skull is often slow, which can result in an abnormally small head size (microcephaly). People with this form of GLUT1 deficiency syndrome may have developmental delay or intellectual disability. Most affected individuals also have other neurological problems, such as stiffness caused by abnormal tensing of the muscles (spasticity), difficulty in coordinating movements (ataxia), and speech difficulties (dysarthria). Some experience episodes of confusion, lack of energy (lethargy), headaches, or muscle twitches (myoclonus), particularly during periods without food (fasting).

About 10 percent of individuals with GLUT1 deficiency syndrome have a form of the disorder often known as non-epileptic GLUT1 deficiency syndrome, which is usually less severe than the common form. People with the non-epileptic form do not have seizures, but they may still have developmental delay and intellectual disability. Most have movement problems such as ataxia or involuntary tensing of various muscles (dystonia); the movement problems may be more pronounced than in the common form.

Several conditions that were originally given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9); paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18); and certain types of epilepsy. In rare cases, people with variants of GLUT1 deficiency syndrome produce abnormal red blood cells and have uncommon forms of a blood condition known as anemia, which is characterized by a shortage of red blood cells.  https://medlineplus.gov/genetics/condition/glut1-deficiency-syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for GLUT1 deficiency syndrome in Orphanet.

Professional guidelines

PubMed

Zimmern V, Korff C
Curr Opin Pediatr 2022 Dec 1;34(6):538-543. Epub 2022 Sep 9 doi: 10.1097/MOP.0000000000001170. PMID: 36081356Free PMC Article
Falsaperla R, Sciuto L, La Spina L, Sciuto S, Praticò AD, Ruggieri M
Metab Brain Dis 2021 Dec;36(8):2195-2203. Epub 2021 Aug 17 doi: 10.1007/s11011-021-00798-1. PMID: 34403026Free PMC Article
Brockmann K
Dev Med Child Neurol 2011 Jul;53(7):580-1. Epub 2011 May 18 doi: 10.1111/j.1469-8749.2011.03946.x. PMID: 21585366

Recent clinical studies

Etiology

Olivotto S, Freddi A, Previtali R, Mauri A, Cereda C, De Amicis R, Bertoli S, Doneda C, Veggiotti P
Pediatr Neurol 2024 Aug;157:118-126. Epub 2024 Jun 4 doi: 10.1016/j.pediatrneurol.2024.05.024. PMID: 38914025
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Mullen SA, Berkovic SF; ILAE Genetics Commission
Epilepsia 2018 Jun;59(6):1148-1153. Epub 2018 May 9 doi: 10.1111/epi.14042. PMID: 29741207
De Giorgis V, Varesio C, Baldassari C, Piazza E, Olivotto S, Macasaet J, Balottin U, Veggiotti P
J Child Neurol 2016 Aug;31(9):1174-80. Epub 2016 Jun 1 doi: 10.1177/0883073816650033. PMID: 27250207
Lebon S, Suarez P, Alija S, Korff CM, Fluss J, Mercati D, Datta AN, Poloni C, Marcoz JP, Campos-Xavier AB, Bonafé L, Roulet-Perez E
Eur J Paediatr Neurol 2015 Mar;19(2):170-5. Epub 2014 Dec 11 doi: 10.1016/j.ejpn.2014.11.009. PMID: 25532859

Diagnosis

Falsaperla R, Sciuto L, La Spina L, Sciuto S, Praticò AD, Ruggieri M
Metab Brain Dis 2021 Dec;36(8):2195-2203. Epub 2021 Aug 17 doi: 10.1007/s11011-021-00798-1. PMID: 34403026Free PMC Article
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Koch H, Weber YG
Epilepsy Behav 2019 Feb;91:90-93. Epub 2018 Jul 31 doi: 10.1016/j.yebeh.2018.06.010. PMID: 30076047
Mullen SA, Berkovic SF; ILAE Genetics Commission
Epilepsia 2018 Jun;59(6):1148-1153. Epub 2018 May 9 doi: 10.1111/epi.14042. PMID: 29741207
Kossoff EH, Veggiotti P, Genton P, Desguerre I
Epilepsia 2014 Aug;55 Suppl 3:37-40. doi: 10.1111/epi.12709. PMID: 25209085

Therapy

Daida T, Shin BC, Cepeda C, Devaskar SU
Nutrients 2024 Jul 21;16(14) doi: 10.3390/nu16142363. PMID: 39064806Free PMC Article
Falsaperla R, Sciuto L, La Spina L, Sciuto S, Praticò AD, Ruggieri M
Metab Brain Dis 2021 Dec;36(8):2195-2203. Epub 2021 Aug 17 doi: 10.1007/s11011-021-00798-1. PMID: 34403026Free PMC Article
Tang M, Park SH, De Vivo DC, Monani UR
Ann Clin Transl Neurol 2019 Sep;6(9):1923-1932. Epub 2019 Aug 28 doi: 10.1002/acn3.50881. PMID: 31464092Free PMC Article
Klepper J, Leiendecker B, Heussinger N, Lausch E, Bosch F
Neuropediatrics 2016 Apr;47(2):132-6. Epub 2016 Feb 22 doi: 10.1055/s-0036-1572413. PMID: 26902182
Gras D, Roze E, Caillet S, Méneret A, Doummar D, Billette de Villemeur T, Vidailhet M, Mochel F
Rev Neurol (Paris) 2014 Feb;170(2):91-9. Epub 2013 Nov 20 doi: 10.1016/j.neurol.2013.09.005. PMID: 24269118

Prognosis

Colpaert M, Singh PK, Donohue KJ, Pires NT, Fuller DD, Corti M, Byrne BJ, Sun RC, Vander Kooi CW, Gentry MS
Neurotherapeutics 2024 Sep;21(5):e00446. Epub 2024 Sep 14 doi: 10.1016/j.neurot.2024.e00446. PMID: 39277505Free PMC Article
Veneruzzo GM, Loos MA, Armeno M, Alonso CN, Caraballo RH
Arch Argent Pediatr 2023 Feb 1;121(1):e202202677. Epub 2022 Nov 3 doi: 10.5546/aap.2022-02677.eng. PMID: 36315575
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Deng D, Xu C, Sun P, Wu J, Yan C, Hu M, Yan N
Nature 2014 Jun 5;510(7503):121-5. Epub 2014 May 18 doi: 10.1038/nature13306. PMID: 24847886
Klepper J, Leiendecker B
Dev Med Child Neurol 2007 Sep;49(9):707-16. doi: 10.1111/j.1469-8749.2007.00707.x. PMID: 17718830

Clinical prediction guides

Olivotto S, Freddi A, Previtali R, Mauri A, Cereda C, De Amicis R, Bertoli S, Doneda C, Veggiotti P
Pediatr Neurol 2024 Aug;157:118-126. Epub 2024 Jun 4 doi: 10.1016/j.pediatrneurol.2024.05.024. PMID: 38914025
Corradini M, Zanaboni MP, Varesio C, Celario M, Capelli E, Giudice C, Quaranta CA, Mensi MM, Pasca L, De Giorgis V
Eur J Paediatr Neurol 2024 Jul;51:62-70. Epub 2024 May 29 doi: 10.1016/j.ejpn.2024.05.010. PMID: 38851145
Markussen KH, Corti M, Byrne BJ, Vander Kooi CW, Sun RC, Gentry MS
J Neurochem 2024 May;168(5):728-743. Epub 2023 Aug 9 doi: 10.1111/jnc.15926. PMID: 37554056Free PMC Article
Falsaperla R, Sciuto L, La Spina L, Sciuto S, Praticò AD, Ruggieri M
Metab Brain Dis 2021 Dec;36(8):2195-2203. Epub 2021 Aug 17 doi: 10.1007/s11011-021-00798-1. PMID: 34403026Free PMC Article
Pellegrin S, Cantalupo G, Opri R, Dalla Bernardina B, Darra F
Eur J Paediatr Neurol 2017 May;21(3):580-582. Epub 2017 Jan 17 doi: 10.1016/j.ejpn.2017.01.002. PMID: 28129950

Recent systematic reviews

Mastrangelo M, Manti F, Ricciardi G, Cinnante EMC, Cameli N, Beatrice A, Tolve M, Pisani F
Eur J Pediatr 2024 Sep;183(9):3665-3678. Epub 2024 Jul 2 doi: 10.1007/s00431-024-05657-6. PMID: 38954008Free PMC Article
Chen J, Jin L, Lin N
Neurol Sci 2024 Sep;45(9):4539-4547. Epub 2024 Apr 8 doi: 10.1007/s10072-024-07519-3. PMID: 38589768
Falsaperla R, Sciuto L, La Spina L, Sciuto S, Praticò AD, Ruggieri M
Metab Brain Dis 2021 Dec;36(8):2195-2203. Epub 2021 Aug 17 doi: 10.1007/s11011-021-00798-1. PMID: 34403026Free PMC Article
Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA
J Neurol 2014 Mar;261(3):589-99. Epub 2014 Jan 12 doi: 10.1007/s00415-014-7240-z. PMID: 24413642
Leen WG, Wevers RA, Kamsteeg EJ, Scheffer H, Verbeek MM, Willemsen MA
JAMA Neurol 2013 Nov;70(11):1440-4. doi: 10.1001/jamaneurol.2013.3090. PMID: 23999624

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