Rare Hematology News

Disease Profile

Glucose transporter type 1 deficiency syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G93.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

GLUT1 deficiency syndrome; Encephalopathy due to GLUT1 deficiency; Glucose transport defect, blood-brain barrier;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

Glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome) is an inherited condition that affects the nervous system. Signs and symptoms generally develop within the first few months of life and may include recurrent seizures (epilepsy) and involuntary eye movements. Affected people may also have microcephaly (unusually small head size) that develops after birth, developmental delay, intellectual disability and other neurological problems such as spasticity, ataxia (difficulty coordinating movements), and dysarthria. Approximately 10% of affected people have the "non-epileptic" form of GLUT1 deficiency syndrome which is associated with all the typical symptoms of the condition without seizures.[1][2] GLUT1 deficiency syndrome is caused by changes (mutations) in the SLC2A1 gene and is inherited in an autosomal dominant manner. Although there is currently no cure for GLUT1 deficiency syndrome, a special diet (called a ketogenic diet) may help alleviate symptoms.[3]

Symptoms

The most common form of glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome), called the classic type, may be characterized by:[1][3][2]

  • Recurrent seizures (epilepsy) beginning in the first months of life
  • Microcephaly (unusually small head size) that develops after birth
  • Developmental delay
  • Intellectual disability
  • Speech and language impairment
  • Movement abnormalities (i.e. involuntary eye movements, spasticity, ataxia, dystonia)
  • Behavioral problems

Other signs and symptoms may include headaches, confusion, loss of energy and/or myoclonus (muscle twitches).[1]

Approximately 10% of affected people have the non-epileptic form of GLUT1 deficiency syndrome. This form is associated with all the typical symptoms of the condition without seizures.[1][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal erythrocyte morphology
0001877
Ataxia
0001251
Dystonia
0001332
EEG abnormality
0002353
Encephalopathy
0001298
Global developmental delay
0001263
Hypoglycorrhachia
Low glucose levels in cerebral spinal fluid
0011972
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Status epilepticus
Repeated seizures without recovery between them
0002133
30%-79% of people have these symptoms
Choreoathetosis
0001266
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Cyanosis
Blue discoloration of the skin
0000961
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Dysarthria
Difficulty articulating speech
0001260
Extrapyramidal dyskinesia
0007308
Generalized hyperreflexia
0007034
Headache
Headaches
0002315
Hemiparesis
Weakness of one side of body
0001269
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Lethargy
0001254
Muscle stiffness
0003552
Paralysis
Inability to move
0003470
Paroxysmal involuntary eye movements
0007704
Seizure
0001250
5%-29% of people have these symptoms
Apraxia
0002186
Autosomal recessive inheritance
0000007
Central apnea
0002871
Myoclonus
0001336
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Autosomal dominant inheritance
0000006
Babinski sign
0003487
Hyperreflexia
Increased reflexes
0001347
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Paroxysmal dystonia
0002268
Paroxysmal lethargy
0011973
Postnatal microcephaly
0005484
Specific learning disability
0001328

Cause

Glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome) is caused by changes (mutations) in the SLC2A1 gene. This gene encodes a protein that helps transport glucose (a simple sugar) into cells where it is used as fuel. The protein is particularly important in the central nervous system since glucose is the brain's main source of energy. SLC2A1 mutations impair the function of the protein. This significantly reduces the amount of glucose available to brain cells leading to the many signs and symptoms associated with GLUT1 deficiency syndrome.[1][4]

Diagnosis

A diagnosis of glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome) is often suspected based on the presence of characteristic signs and symptoms. Additional testing can then be ordered to confirm the diagnosis. This may include a lumbar puncture, specialized blood tests to measure the blood concentration of glucose and genetic testing.[3][2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is currently no cure for glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome); however, a special diet (called a ketogenic diet) may help control symptoms in some affected people.[3] The GLUT1 Deficiency Foundation offers an information page with detailed information regarding the ketogenic diet. Please click on the link to access this resource.

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

        • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • Genetics Home Reference (GHR) contains information on Glucose transporter type 1 deficiency syndrome. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Glucose transporter type 1 deficiency syndrome. Click on the link to view a sample search on this topic.

              References

              1. GLUT1 deficiency syndrome. Genetics Home Reference. March 2014; https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome.
              2. Glucose Transporter Type 1 Deficiency Syndrome. NORD. 2014; https://rarediseases.org/rare-diseases/glucose-transporter-type-1-deficiency-syndrome/.
              3. Dong Wang, MD, Juan M Pascual, MD, PhD, and Darryl De Vivo, MD. Glucose Transporter Type 1 Deficiency Syndrome. GeneReviews. January 2015; https://www.ncbi.nlm.nih.gov/books/NBK1430/#glut1.Clinical_Description.
              4. What is Glut1 Deficiency?. GLUT1 Deficiency Foundation. https://www.g1dfoundation.org/what-is-glut1-deficiency/what-is-glut1-deficiency/. Accessed 12/7/2015.

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