Glucose transporter type 1 deficiency syndrome

Alternate names

GLUT1 deficiency syndrome; Encephalopathy due to GLUT1 deficiency; Glucose transport defect, blood-brain barrier; De Vivo disease; GLUT-1 deficiency syndrome; Glucose transporter protein syndrome; GLUT1 DS; G1D

Definition

Glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome) is an inherited condition that affects the nervous system.

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.

Epidemiology

GLUT1 deficiency syndrome is a rare disorder. Approximately 500 cases have been reported worldwide since the disorder was first identified in 1991. In Australia, the prevalence of the disorder has been estimated at 1 in 90,000 people. However, researchers suggest that the disorder may be underdiagnosed, because many neurological disorders can cause similar symptoms.

Cause

• GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene.
• This gene provides instructions for producing a protein called the glucose transporter protein type 1 (GLUT1).
• The GLUT1 protein is embedded in the outer membrane surrounding cells, where it transports a simple sugar called glucose into cells from the blood or from other cells for use as fuel.
• In the brain, the GLUT1 protein is involved in moving glucose, which is the brain's main energy source, across the blood-brain barrier.
• The blood-brain barrier acts as a boundary between tiny blood vessels (capillaries) and the surrounding brain tissue; it protects the brain's delicate nerve tissue by preventing many other types of molecules from entering the brain.
• The GLUT1 protein also moves glucose between cells in the brain called glia, which protect and maintain nerve cells (neurons).

Gene mutations

• SLC2A1 gene mutations reduce or eliminate the function of the GLUT1 protein.
• Having less functional GLUT1 protein reduces the amount of glucose available to brain cells, which affects brain development and function.

Inheritance

• This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 90 percent of cases of GLUT1 deficiency syndrome result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from an affected parent.
• In a small number of families, GLUT1 deficiency syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

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

• 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).

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal erythrocyte morphology
• Ataxia
• Dystonia
• EEG abnormality
• Encephalopathy
• Global developmental delay
• Hypoglycorrhachia(Low glucose levels in cerebral spinal fluid)
• Progressive microcephaly(Progressively abnormally small cranium)
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)
• Status epilepticus(Repeated seizures without recovery between them)

30%-79% of people have these symptoms

• Choreoathetosis
• Confusion(Disorientation)
• Cyanosis(Blue discoloration of the skin)
• Delayed speech and language development(Deficiency of speech development)
• Dysarthria(Difficulty articulating speech)
• Extrapyramidal dyskinesia
• Generalized hyperreflexia
• Headache(Headaches)
• Hemiparesis(Weakness of one side of body)
• Intellectual disability(Mental deficiency)
• Lethargy
• Muscle stiffness
• Paralysis(Inability to move)
• Paroxysmal involuntary eye movements
• Seizure

5%-29% of people have these symptoms

• Apraxia
• Autosomal recessive inheritance
• Central apnea
• Myoclonus
• Sleep disturbance(Difficulty sleeping)
• Strabismus(Cross-eyed)

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.

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.

NIH genetic and rare disease info

• NIH info on Glucose transporter type 1 deficiency syndrome

Glucose transporter type 1 deficiency syndrome is a rare disease.

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