Key Terms in Glut1 Deficiency
This is a complex and rare disease that can impact patients in a number of ways. It is important to understand as much as possible about Glut1 Deficiency and the key terms associated with it.
also known as Glucose Transporter Type 1 Deficiency Syndrome, G1D, Glut1DS, De Vivo Disease
a rare genetic metabolic disorder characterized by deficiency or malfunction of a protein (Glut1) that is required for glucose (a simple sugar and the primary energy source) to cross the blood-brain barrier. The resulting metabolic crisis can create a spectrum of symptoms in varying combinations and a broad range of severity.
Aberrant Gaze Saccades or Intermittent Involuntary Gaze (IIG)
rapid, repetitive, multidirectional eye movements often accompanied by a head movement in the same direction. These events sometimes occur in very young Glut1 Deficiency patients and resemble opsoclonus or nystagmus. They are often the first symptom noticed by family members.
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Attention Deficit Hyperactivity Disorder (ADHD)
a combination of problems that may include difficulty sustaining attention or focus, hyperactivity, and impulsive behavior.
Blood Brain Barrier
a filtering and protective mechanism of the capillaries that carry blood to the brain and spinal cord tissue, blocking the passage of certain substances.
an energy-rich ketone body derived from fat which can be utilized by tissues and cross the blood-brain barrier during periods of glucose deficiency. It can be measured in blood and urine.
an altered state of consciousness characterized by inability to engage in orderly thought or by lack of power to distinguish, choose, or act decisively.
the quality or state of being defective or of lacking something that is necessary
not reaching cognitive or physical developmental milestones at the expected time.
difficulty swallowing, taking more time and effort to move food or liquid from mouth to stomach.
a medical condition with recurring seizures.
sporadic, having symptom-free periods that alternate with the presence of symptoms.
an inheritable medical condition caused by a DNA abnormality.
- Autosomal Dominant
a pattern of inheritance where only one copy (from one parent) of the abnormal gene is necessary for the disorder or trait to develop. Glut1 Deficiency is autosomal dominant.
- Autosomal Recessive
a pattern of inheritance where two copies (from both parents) of an abnormal gene must be present in order for the disorder or trait to develop.
- De Novo Variant
an alteration in a gene that is present for the first time in one family member as a result of an error in the copying of genetic material or an error in cell division.
a condition existing at or before birth.
the fundamental unit of heredity; a specific section of DNA within a chromosome.
- Gene Sequencing
analysis of a DNA sample to determine makeup and to look for deletions or mutations.
- Genetic Variant
a permanent change in the DNA sequence such that the sequence differs from what is found in most people.
an organism’s complete set of DNA, including all of its genes.
an individual’s collection of genes and genetic identity.
the observable physical characteristics of an individual.
- SLC2A1 gene: solute carrier family 2 (facilitated glucose transporter), member 1
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.
- Variant of Unknown Significance (VUS)
a genetic change where the impact on the individual is not yet known
the main type of sugar in the blood and the major source of energy for the body's cells. Glucose comes from the foods we eat or the body can make it from other substances. Glucose is carried to the cells through the bloodstream.
abbreviation for glucose transporter protein type 1. Glut1 is one of fourteen glucose transporters found in almost every tissue with varying expression levels in different cell types. GLUT1 facilitates the transport of glucose across the plasma membranes of mammalian cells.
abnormally increased breakdown of red blood cells.
a high-fat, adequate-protein, low-carbohydrate dietary therapy that causes the body to burn fat for energy in the absence of glucose. Ketogenic diets are the recommended treatment for Glut1 Deficiency, since ketones can cross the blood brain barrier and provide energy and nourishment as an alternative to glucose. Classical, Modified Ketogenic, Modified Atkins, MCT Oil Diet, and Low Glycemic Index Treatment are all different versions of ketogenic diets. Please visit The Charlie Foundation's website for more information on ketosis and the different types of diets used to achieve it.
substances that are made when the body breaks down fat for energy or fuel as opposed to glucose. Ketone bodies produced are acetone, acetoacetate, and beta-hydroxybutyrate.
a metabolic process that occurs when the body does not have enough glucose for energy. Fats are broken down for energy, resulting in the production of acids called ketones within the body.
neurologically-based problems that affect the brain’s ability to receive, process, analyze, or store information. Learning disabilities can interfere with learning basic skills such as reading, writing and/or math and with higher level skills such as organization, time planning, abstract reasoning, long or short term memory and attention.
reduced level of consciousness marked by listlessness, drowsiness, and apathy.
Low Tone (hypotonia)
a state of low muscle tone often accompanied by reduced muscle strength. Muscles may seem “floppy”, joints may seem loose or overly flexible, and poor posture, coordination, balance, and body awareness can result.
Lumbar Puncture (spinal tap)
a procedure to collect and analyze the fluid (cerebrospinal fluid, or CSF) surrounding the brain and spinal cord. During a lumbar puncture, a needle is carefully inserted into the spinal canal low in the back (lumbar area) and samples of spinal fluid are collected.
Modified Atkins Diet (MAD)
a ketogenic dietary therapy that is less restrictive than the classical ketogenic diet. It is a mix between the Atkins diet and a classical ketogenic approach, and approximates a 1:1 ratio of fat to carbohydrate and protein.
MCT oil (medium chain triglycerides)
fatty acids composed of 6 – 12 carbon atoms. Oils can contain short chain, medium chain, or long chain fatty acids. Most oils are a combination of all three types. Medium chain oils are thought to be more ketogenic.
complex headaches that are usually characterized by severe pain on one or both sides of the head, an upset stomach, and, at times, disturbed vision.
a neurological condition that occurs when the head circumference is smaller than normal, associated with impaired brain growth and development.
Glut1 Deficiency patients can often experience complex and unique movement episodes that resemble the following types, but can also be unique and difficult to classify.
difficulty in coordinating movements; can include gait abnormality. Ataxia implies dysfunction of the portion of the nervous system that controls movement.
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a symptom characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet. In some cases it can affect the arms, legs, neck and tongue.
repetitive, persistent, random, involuntary flinging movements, usually involving the limbs.
abnormal involuntary movements. These are characterized by brief, irregular contractions that are not repetitive or rhythmic, but appear to flow from one muscle to the next and can occur at rest or when awake.
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a category of movement disorders that are characterized by involuntary muscle movements.
a developmental coordination disorder affecting fine and/or gross motor coordination in children and adults. It may also affect speech.
uncontrollable and sometimes painful muscle spasms caused by incorrect signals from the brain. It can affect the entire body or isolated parts of the body. Dystonia 9 and 18 are both associated with Glut1 Deficiency and the SLC2A1 gene.
sudden, rapid, brief, involuntary jerking or spasm of a muscle or group of muscles.
- Paroxysmal Exercise Induced Dyskinesia (PED)
dyskinesias (involuntary muscle movements) induced by prolonged exercise or physical exertion.
abnormal tensing of the muscles that can cause stiffness or tightness of the muscles and can interfere with normal movement, speech, and gait.
an involuntary trembling or shaking movement, often rhythmic, in one or more body parts.
a sudden attack, recurrence, or intensification of a disease.
sudden disruption of normal brain electrical activity and cell communication. Recurrent seizures are known as epilepsy. Seizures may also be classed as motor or non-motor, depending on whether physical movement is involved.
- Absence seizure
brief loss of consciousness (staring episode).
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- Atonic seizure
a sudden and brief loss of muscle tone (also known as akinetic or drop attack). Patients become floppy and often fall during an atonic seizure, usually forwards.
- Clonic seizure
repetitive, rhythmic jerking movements of the body, often on both sides and in the arms and legs.
- Focal Aware seizure
seizures that begin and are confined to limited and specific areas of the brain, but consciousness is not affected. Patients are aware and alert, will usually know something has happened and will remember the seizures afterwards.
- Focal Impaired Awareness seizure
seizures that begin and are confined to limited and specific areas of the brain. Consciousness is affected, confusion may be present, and patients may be able to hear, but not fully understand or be able to respond.
- Generalized seizure
seizures that appear to start in all parts of the brain simultaneously and have no identifiable onset or warning, consciousness is altered.
- Myoclonic seizure
sudden, rapid, brief, involuntary jerking or spasm of a muscle or group of muscles. Myoclonic jerks or movements are not always due to epilepsy.
- Tonic seizure
tone is greatly increased and the body, arms, or legs make sudden stiffening movements. Patients often fall during a tonic seizure, usually backwards.
- Tonic-clonic seizure
a convulsive seizure that begins with muscle tensing and tightening and loss of consciousness followed by jerking movements in the arms and legs.
conditions that cause problems creating or forming the speech sounds needed to communicate with others.
an impairment of language, affecting the production or comprehension of speech and the ability to read or write.
a speech disorder where messages from the brain to the mouth are disrupted, and the lips or tongue are unable to be moved to the right place to say sounds correctly, even though the muscles are not weak.
complete lack of speech.
impairment of the ability to produce smooth, fluent speech.
difficult or unclear articulation of speech that is otherwise linguistically normal.
Triheptanoin or C7 oil
a medium chain triglyceride oil (a fat) uniquely composed of an odd-numbered fatty acid chain. Triheptanoin is currently under investigation as a therapy for Glut1 Deficiency.