[3] This birth incidence translates to an estimated prevalence of 3,000 to 7,000 in the U.S.[2] GLUT1 deficiency is characterized by an array of signs and symptoms including mental and motor developmental delays, infantile seizures refractory to anticonvulsants, ataxia, dystonia, dysarthria, opsoclonus, spasticity, other paroxysmal neurologic phenomena and sometimes deceleration of head growth also known as microcephaly.
[5] Other seizure types may occur, including generalized tonic clonic, focal, myoclonic, atypical absence, atonic or unclassified.
[5] Mothers of infants with this disorder usually have uneventful pregnancies and deliveries, with the child appearing normal and within typical birth weight and length ranges.
[8] The syndrome can cause infantile seizures refractory to anticonvulsive drugs, developmental delay, acquired microcephaly and neurologic manifestations including spasticity, hypotonia and ataxia.
Walking may be delayed or difficult because legs are stiff (spasticity), balance is poor (ataxia) or posture is twisted (dystonia).
The symptom picture for each patient may evolve and change over time as children with GLUT1 deficiency grow and develop through adolescence and into adulthood.
The GLUT1 protein that transports glucose across the blood brain barrier is encoded by the SLC2A1 gene, located on chromosome 1.
[18] GLUT1 deficiency is diagnosed based on the clinical features in combination with determining the glucose concentration in the CSF and/or a genetic analysis through a lumbar puncture (spinal tap).
[19] A highly specialized lab test called the red blood cell uptake assay may confirm GLUT1 deficiency but is not commercially available.
Ketone bodies are transported across the blood-brain barrier by other means than the GLUT1 protein and thus serve as an alternative fuel for the brain when glucose is not available.
In addition, some critical symptoms, including cognitive deficits and certain movement difficulties, tend to persist in GLUT1 deficiency patients treated by a ketogenic diet, raising the question whether GLUT1 deficiency is caused simply by a lack of proper brain energy or if there are more complicated and widespread systems and processes affected.
[18] The ketogenic diet must be carefully crafted and tailored to meet the needs of each patient and reduce the risk of side effects.
It should only be used under the care of medical professionals and dietitians, and it may take some time to establish the ideal ratio of fat versus proteins and carbohydrates and other diet variables for each individual patient to experience optimal tolerance and benefits.
[18] Ketone esters are an area of dietary therapy currently under investigation for potential treatment of GLUT1 deficiency and other medical conditions.
Ketone esters have been shown in recent research to improve seizures and movement disorders in GLUT1 deficient mice, but human studies have not yet been conducted.
[18] is an investigational pharmaceutical-grade medical food that has shown potential as a treatment for a number of inherited metabolic diseases.
[18] A phase 3 clinical trial however failed to find an improvement in patients with GLUT1 DS with disabling movement disorders.
[24][25] Therapies and rehabilitative services are beneficial since most GLUT1 deficiency patients experience movement disturbances as well as speech and language disorders.