Childhood Onset GLUT1 Deficiency Syndrome 2 (GLUT1DS2)

Childhood onset GLUT1 deficiency syndrome 2 (GLUT1DS2) is a rare brain disease that starts in childhood and mainly causes short attacks of strange movements in the arms or legs when the child exercises. These attacks are called “paroxysmal exercise-induced dyskinesia,” which means sudden, repeat episodes of abnormal movements triggered by exercise.MalaCards+1

Childhood onset GLUT1 deficiency syndrome 2 (also called GLUT1DS2, DYT18 or paroxysmal exercise-induced dyskinesia) is a rare genetic brain energy disease. A spelling change (mutation) in the SLC2A1 gene makes the GLUT1 protein work poorly. GLUT1 normally moves glucose (sugar fuel) from the blood into the brain. When GLUT1 does not work well, the brain does not get enough sugar. This causes short attacks of abnormal movements after exercise, and sometimes childhood absence seizures and learning problems. MalaCards+2ncbi.nlm.nih.gov+2

The problem happens because the brain does not get enough glucose (sugar), which is its main fuel. Glucose reaches the brain through a special protein called GLUT1, which sits in the blood–brain barrier (the wall of blood vessels that protect the brain). In GLUT1DS2, this GLUT1 protein does not work properly, so less glucose enters the brain, and brain cells do not get enough energy.ncbi.nlm.nih.gov+1

GLUT1DS2 is caused by a change (mutation) in a gene called SLC2A1. This gene tells the body how to make the GLUT1 transporter. When the gene has a harmful change, the GLUT1 protein is faulty or reduced, and glucose transport into the brain is lower than normal.University of Chicago Genetic Services+1

This condition is usually inherited in an autosomal dominant way. This means one changed copy of the SLC2A1 gene, from either the mother or the father, is enough to cause the disease. Sometimes the gene change appears for the first time in the child (a de novo mutation), and parents are not affected.MalaCards+1

Children with GLUT1DS2 can have movement attacks, absence seizures (short staring spells), mild learning or thinking problems, and sometimes blood problems like mild hemolytic anemia in some families. Between attacks, many children may look almost normal or only mildly affected, so the disease can be missed for years.MalaCards+1

Other Names and Types

Doctors and researchers use several other names for this condition. These names all point to almost the same disease pattern.ncbi.nlm.nih.gov+1

Other names include:

• Childhood-onset GLUT1 deficiency syndrome 2

• GLUT1 deficiency syndrome 2 (GLUT1DS2)

• Dystonia 18 (DYT18)

• Paroxysmal exercise-induced dyskinesia (PED)

• Paroxysmal exertion-induced dyskinesia

• Paroxysmal exercise-induced dystonia

• PED with or without epilepsy and/or hemolytic anemia

• PxMD-SLC2A1 (paroxysmal movement disorder due to SLC2A1)ncbi.nlm.nih.gov+1

These names reflect different key features: “paroxysmal” means sudden and brief, “exercise-induced” means triggered by exercise, “dyskinesia” and “dystonia” mean abnormal movements or postures, and “dystonia 18” is the number given to this genetic form of dystonia.Disease Ontology+1

Types or clinical patterns doctors may describe:

• A type where movement attacks are the main problem and seizures are few or absent.MalaCards+1

• A type with movement attacks plus childhood absence epilepsy, where the child often has brief staring spells starting around 2–3 years of age.MalaCards+1

• A type with movement attacks plus mild learning or thinking problems, where school difficulty and slow processing are more visible than seizures.MalaCards+1

These “types” are not strict official categories but useful ways for doctors to describe the range of symptoms in children with GLUT1DS2.Seizure Journal+1

Causes of Childhood Onset GLUT1 Deficiency Syndrome 2

The true root cause of GLUT1DS2 is always related to a problem in brain glucose transport. Most causes below are different kinds of changes or mechanisms that affect the SLC2A1 gene and GLUT1 protein. A few points also describe why episodes become worse or more frequent once the disease is present.

1. Pathogenic mutation in the SLC2A1 gene
   The main cause is a disease-causing mutation in SLC2A1, the gene that makes the GLUT1 transporter. This mutation reduces the amount or function of GLUT1 and lowers glucose entry into the brain.University of Chicago Genetic Services+1

2. Missense mutation in SLC2A1
   A missense mutation changes one “letter” in the DNA code and swaps one amino acid in the GLUT1 protein. Even this small change can distort the transporter’s shape and make glucose transport less efficient.University of Chicago Genetic Services+1

3. Nonsense mutation in SLC2A1
   A nonsense mutation introduces a “stop” signal too early in the gene. This leads to a short, incomplete GLUT1 protein that cannot work properly, so glucose transport into the brain falls.University of Chicago Genetic Services+1

4. Frameshift mutation in SLC2A1
   When one or more DNA bases are added or deleted, the reading frame shifts. This usually produces a totally altered GLUT1 protein and severely reduces glucose transport.University of Chicago Genetic Services+1

5. Splice-site mutation in SLC2A1
   Some mutations occur where the gene’s coding parts are joined. These splice-site changes can cause loss or mixing of important sections of the GLUT1 protein, which again lowers transporter function.University of Chicago Genetic Services+1

6. Regulatory or promoter mutations in SLC2A1
   Rare changes in non-coding regions (like the promoter or 5′-UTR) can reduce how much SLC2A1 gene is “turned on.” This results in fewer GLUT1 proteins in the blood-brain barrier and less glucose delivery to the brain.Nature+1

7. De novo (new) SLC2A1 mutation in the child
   In many children, the mutation is not present in either parent and appears for the first time in the child. This new mutation still disrupts GLUT1 and causes the disease even when family history is negative.MDPI+1

8. Inherited autosomal dominant SLC2A1 mutation
   In some families, one parent carries the mutation and passes it on. The parent may have mild or even no obvious symptoms, but the child can still develop GLUT1DS2.MDPI+1

9. Haploinsufficiency of GLUT1
   Many patients have only one healthy copy of the SLC2A1 gene, so the total GLUT1 made is about half of normal. This “haploinsufficiency” is enough to reduce glucose transport and cause brain energy shortage.MDPI

10. Misfolding and instability of GLUT1 protein
    Some mutations cause GLUT1 to fold wrongly or become unstable. Misfolded proteins may be broken down quickly inside the cell, leaving fewer functional transporters on the blood–brain barrier.MDPI

11. Poor trafficking of GLUT1 to the cell surface
    Certain variants allow GLUT1 to be made but prevent it from reaching the cell membrane where it must sit to move glucose. This mis-trafficking again reduces effective glucose transport into the brain.MDPI+1

12. Mosaicism in a parent
    In some families, a parent may carry the mutation in only some body cells (mosaicism). This can lead to a mildly affected or symptom-free parent and an affected child, but the molecular cause is still the SLC2A1 mutation.MDPI+1

13. Other rare gene variants affecting GLUT1 function
    A few children with GLUT1-like symptoms do not show clear SLC2A1 mutations. Researchers think other rare gene changes may indirectly affect GLUT1 expression or brain energy pathways.www.elsevier.com+1

14. Overall low CSF glucose (hypoglycorrhachia) in classic cases
    Many patients with GLUT1 deficiency syndromes show low cerebrospinal fluid (CSF) glucose compared with blood. This low CSF glucose reflects the basic cause: poor glucose movement across the blood–brain barrier.PMC+1

15. Energy crisis in brain cells
    Because glucose is the main fuel, low brain glucose leads to an “energy crisis” for neurons. This energy lack is a direct cause of seizures, movement attacks, and other brain symptoms.ncbi.nlm.nih.gov+1

16. Exercise as a trigger of attacks (not the root cause)
    Prolonged walking or running increases energy demand in muscles and brain. In GLUT1DS2, the already low brain energy supply cannot keep up, so abnormal movements appear. Exercise does not cause the disease but triggers symptoms.MalaCards+1

17. Fasting or delayed meals (symptom trigger)
    If a child with GLUT1DS2 does not eat regularly, blood glucose can fall. Because glucose entry to the brain is already poor, fasting can trigger more frequent or severe attacks. Again, fasting is a trigger, not the primary cause.ncbi.nlm.nih.gov+1

18. Illness, fever, or stress (symptom trigger)
    Infections and stress increase body and brain energy needs. In GLUT1DS2, this can push an already fragile energy system over the limit and cause a cluster of dyskinesia episodes or seizures.Frontiers+1

19. Lack of alternative brain fuel (such as ketones)
    In untreated patients who are not on a ketogenic diet, the brain depends almost fully on glucose. Without enough glucose or ketones, the energy problem is worse and leads to more symptoms.Seizure Journal

20. Delays in diagnosis and treatment (worsening of effects)
    The underlying gene mutation is present from birth, but if diagnosis and diet treatment are delayed, long-term energy shortage can gradually harm brain development and lead to more fixed problems.Seizure Journal+1

Symptoms of Childhood Onset GLUT1 Deficiency Syndrome 2

Children with GLUT1DS2 can show many different symptoms. Some have mainly movement attacks, some have seizures, and some have both. Symptoms can also vary within the same family.MalaCards+1

1. Paroxysmal exercise-induced dyskinesia in the legs
   The most typical symptom is sudden abnormal movements of the legs after walking, running, or climbing stairs. The child may drag a foot, twist the leg, or have jerky, dance-like movements for minutes to hours, then return to normal.MalaCards+1

2. Abnormal postures (dystonia) during attacks
   During episodes, the child’s foot or hand may turn inward or outward in a fixed, twisted position. This is called dystonia and can make walking hard or impossible until the attack passes.MalaCards+1

3. Choreoathetoid movements
   Some children have flowing, twisting, writhing movements of the limbs or face during attacks. These choreoathetoid movements look strange but are usually painless and disappear when the attack ends.MalaCards+1

4. Childhood absence seizures
   Many children with GLUT1DS2 have brief staring spells called absence seizures. The child stops what they are doing for a few seconds, stares, may blink, and then continues as if nothing happened. These spells often start around age 2–3 years.MalaCards+1

5. Other seizure types in some patients
   Less often, children may have generalized tonic-clonic seizures (full-body shaking), myoclonic jerks (sudden brief jerks), or focal seizures. Seizures can be hard to control with standard anti-seizure drugs alone.ncbi.nlm.nih.gov+1

6. Mild intellectual or learning problems
   Some children have mild learning delays, attention problems, or slower thinking speed at school. They may need extra help in class even if their movement symptoms are the main visible problem.MalaCards+1

7. Motor development delay in early childhood
   In some cases, babies or toddlers may sit, crawl, or walk later than expected. The delay is often mild but reflects the early effect of poor brain energy on motor learning.ncbi.nlm.nih.gov+1

8. Balance and coordination problems
   Some children have ataxia, which means poor balance and clumsy movements. They may sway when walking, fall easily, or have trouble with fine tasks like writing or using small objects.Seizure Journal+1

9. Fatigue and exercise intolerance
   The child may tire easily with physical activity and complain of heavy legs or difficulty keeping up with friends. This fatigue links to the extra energy demand during exercise in a brain and body that already have reduced glucose supply.movementdisorders.onlinelibrary.wiley.com+1

10. Headaches or migraine-like episodes
    Some children with GLUT1 deficiency syndromes have recurrent headaches or migraines, which may be linked to brain energy imbalance and changes in blood vessels.MDPI+1

11. Speech or language difficulties
    Mild language delay, unclear speech, or trouble finding words can appear. These issues reflect the impact of long-term energy shortage on brain areas that control language and speech.ncbi.nlm.nih.gov+1

12. Worsening of movements with fasting or missed meals
    Parents often notice that attacks happen more often when the child is hungry or has not eaten for a long time. This is because blood glucose falls and the already poor brain fuel supply becomes even lower.Seizure Journal+1

13. Triggering of attacks by long or fast walking
    Even if the child seems fine at rest, a long walk, running, or sports can trigger dyskinesia episodes. This exercise trigger is a key sign that makes doctors think about GLUT1DS2.MalaCards+1

14. Possible hemolytic anemia in some families
    One reported family had GLUT1DS2 plus mild hemolytic anemia, where red blood cells break down faster than normal. This is rare but shows that the disease can also affect blood cells.MalaCards+1

15. Large variation in symptom severity
    Even in the same family, one person may have only mild movement attacks, while another may have both frequent seizures and learning problems. This wide variation is typical of GLUT1DS2.MalaCards+1

Diagnostic Tests for Childhood Onset GLUT1 Deficiency Syndrome 2

Doctors use a mix of clinical observation, bedside tests, lab tests, electrodiagnostic tests, and imaging to diagnose GLUT1DS2 and to exclude other causes of movement disorders and epilepsy.

Physical examination tests

1. Full neurological examination
   The doctor checks the child’s strength, reflexes, muscle tone, sensation, eye movements, and coordination. In GLUT1DS2, the child may appear almost normal between attacks, but subtle signs like mild dystonia or brisk reflexes can be found.ncbi.nlm.nih.gov+1

2. Observation of gait and posture
   The child is asked to walk, run, and sometimes climb stairs while the doctor watches. After some minutes of exercise, the typical abnormal movements or twisted postures of the legs may appear, which strongly suggest paroxysmal exercise-induced dyskinesia.movementdisorders.onlinelibrary.wiley.com+1

3. Exercise-provoked examination
   In clinic, the child may be asked to walk or run in the hallway for a set time. The doctor then examines the legs and arms right after exercise. Reproducible attacks triggered by exertion are a major clue to GLUT1DS2 and related energy disorders.neurology.org+1

4. Developmental and cognitive assessment
   Simple tests of memory, attention, school skills, and developmental milestones help the doctor see if there is any learning delay or mild intellectual disability, which can be part of the GLUT1 deficiency spectrum.ncbi.nlm.nih.gov+1

Manual or bedside functional tests

5. Coordination tests (finger-to-nose and heel-to-shin)
   The child is asked to touch their nose with a finger and then touch the doctor’s finger, or slide the heel down the opposite shin. These simple tests can show clumsiness or incoordination during or after attacks.Turkish Journal of Neurology+1

6. Manual muscle strength testing
   The doctor presses against the child’s arms and legs while the child pushes back. Strength is often normal between attacks in GLUT1DS2, which helps distinguish it from muscle diseases or peripheral nerve problems.Turkish Journal of Neurology+1

7. Hyperventilation during EEG to provoke absence seizures
   During an EEG, the child may be asked to breathe deeply and quickly for a few minutes. This can bring out absence seizures and show the typical EEG pattern, helping to confirm associated childhood absence epilepsy.ncbi.nlm.nih.gov+1

Laboratory and pathological tests

8. Fasting blood glucose test
   A simple blood test checks fasting blood sugar. In GLUT1DS2, blood glucose is often normal, which shows that the problem is not lack of sugar in the blood but poor transport into the brain.ncbi.nlm.nih.gov+1

9. Basic blood tests to exclude other causes
   Doctors often check complete blood count, electrolytes, liver and kidney function, thyroid function, and metabolic markers. These tests help rule out other diseases that can mimic movement disorders or epilepsy.Turkish Journal of Neurology+1

10. Lumbar puncture for CSF glucose
    A lumbar puncture (spinal tap) is done after several hours of fasting to measure glucose in the cerebrospinal fluid (CSF). In many GLUT1 deficiency cases, CSF glucose is low compared with blood. In some milder forms like GLUT1DS2, levels may be closer to normal but can still be relatively low.PMC+1

11. CSF to blood glucose ratio
    Doctors calculate the ratio of CSF glucose to blood glucose taken at the same time. A low ratio (often below about 0.6 and much lower in classic cases) is one of the strongest laboratory clues that GLUT1-related brain energy problems are present.ScienceDirect+1

12. CSF lactate level
    Lactate in the CSF is usually normal or low in GLUT1 deficiency, which helps distinguish it from mitochondrial diseases where lactate is often high. This pattern supports the diagnosis of GLUT1DS.PMC+1

13. Red blood cell glucose uptake assay (specialized test)
    In some centers, a special test measures how much glucose red blood cells take up, because red cells also use GLUT1. Reduced uptake can support the diagnosis when genetic findings are unclear.MDPI+1

14. Targeted SLC2A1 gene sequencing
    This is the key confirmatory test. The SLC2A1 gene is read letter by letter to look for mutations that change or remove parts of the GLUT1 protein. A disease-causing variant confirms the diagnosis of SLC2A1-related GLUT1 deficiency.University of Chicago Genetic Services+1

15. Expanded genetic panels or exome sequencing
    If targeted SLC2A1 testing is negative but suspicion is still high, doctors may order larger gene panels for paroxysmal movement disorders or whole-exome sequencing to look for other rare genetic causes.www.elsevier.com+1

Electrodiagnostic tests

16. Electroencephalogram (EEG)
    EEG records the brain’s electrical activity with small scalp electrodes. It can show absence seizure patterns (like 3-Hz spike-and-wave) or other epileptic discharges in children with GLUT1DS2 and helps guide seizure diagnosis and treatment.ncbi.nlm.nih.gov+1

17. Electromyography (EMG) and nerve conduction studies
    These tests measure the electrical activity of muscles and the speed of nerve signals. In GLUT1DS2, results are often normal, which helps rule out primary muscle or peripheral nerve diseases as the cause of movement symptoms.movementdisorders.onlinelibrary.wiley.com+1

Imaging tests

18. Brain magnetic resonance imaging (MRI)
    MRI produces detailed pictures of the brain. Many children with GLUT1DS2 have a normal MRI, but sometimes mild changes in white matter or brain size may be seen. A normal MRI with typical clinical features still supports a GLUT1 deficiency diagnosis.Seizure Journal+1

19. Functional imaging (PET or SPECT) in special cases
    Positron emission tomography (PET) or single-photon emission computed tomography (SPECT) can show areas of lower glucose use or blood flow in the brain. These tests are not always needed but may help in complex or unclear cases.Seizure Journal+1

20. Brain CT scan for exclusion of other diseases
    A CT scan is less detailed than MRI but can quickly exclude bleeding, large tumors, or major structural problems. It usually looks normal in GLUT1DS2, which again points toward a metabolic and genetic cause rather than a structural brain lesion.Turkish Journal of Neurology+1

Non-pharmacological treatments

Medical ketogenic diet (classic ketogenic diet)
This is a very high-fat, very low-carbohydrate, controlled-protein diet planned by a specialist team. It makes the body produce ketone bodies, which can cross into the brain and act as an alternative fuel instead of glucose. For GLUT1 deficiency, ketogenic diet is the standard of care and often reduces dyskinesia and seizures, and helps attention and development. It needs careful monitoring of growth, cholesterol, kidneys, bones, and possible side effects like constipation or kidney stones. Wiley Online Library+3ScienceDirect+3maedica.ro+3

Modified Atkins ketogenic diet
This diet is a simpler, less strict form of ketogenic therapy. Carbohydrates are limited but not weighed as strictly as in the classic diet. Fat is encouraged and protein is moderate. It can be easier for older children and teenagers to follow, while still producing a steady level of ketones. It may be slightly less powerful than the classic ketogenic diet, but it can improve exercise-induced dyskinesia and seizures in some patients who cannot tolerate the strict version. GLUT1 Deficiency Foundation+2ScienceDirect+2

Low glycemic index treatment (LGIT)
LGIT is another medical diet that focuses on carbohydrates with a low glycemic index, meaning they raise blood sugar slowly. Fats are still relatively high, but less than in a classic ketogenic diet. This option may help when a full ketogenic diet is too difficult for the family. The purpose is to keep blood sugar and ketones stable so that brain energy supply is smoother and movement attacks are less frequent. GLUT1 Deficiency Foundation+2Wiley Online Library+2

Medium-chain triglyceride (MCT)-based ketogenic diet
An MCT diet uses special fats (MCT oil) that turn into ketones more easily than usual fats. Because MCT produces more ketones per calorie, the diet can sometimes allow a little more protein and carbohydrate. This can improve variety and enjoyment of food. The mechanism is the same: provide ketones as brain fuel. MCT diets must be carefully introduced to avoid stomach upset and are usually supervised by a metabolic dietitian. ScienceDirect+2kanso.com+2

Strict meal timing and avoiding long fasting
Children with GLUT1DS2 often have worse symptoms when they are fasting or hungry, because their brain cannot pull in enough glucose and may not have enough ketones. Regular meals and snacks, especially before expected exercise, keep energy steady. The purpose is to prevent deep drops in blood glucose and brain fuel. This simple lifestyle step can clearly reduce paroxysmal dyskinesia episodes. MalaCards+2ncbi.nlm.nih.gov+2

Exercise pacing and rest strategies
In GLUT1DS2, attacks are often triggered by exercise or exertion. Planned activity with built-in rest periods, shorter bursts of exercise, and stopping at the first sign of abnormal movement can reduce attack length and severity. The mechanism is lowering the sudden energy demand from the muscles and brain so that the limited glucose transport does not become critically low. MalaCards+2ncbi.nlm.nih.gov+2

Hydration and electrolyte management around exercise
Good hydration before, during, and after exercise helps maintain blood flow and energy delivery to the brain. Adding oral rehydration solutions if advised by a doctor can keep electrolytes balanced. This may not directly fix GLUT1, but it supports stable blood volume and reduces stress on the nervous system, which can indirectly reduce dyskinesia and headache after exertion. MalaCards+2ScienceDirect+2

Physiotherapy for dystonia and gait problems
Physical therapists can teach stretching, strengthening, and balance exercises to improve posture, gait, and coordination. For children who have abnormal limb movements, targeted therapy can reduce contractures and improve joint range of motion. The mechanism is mainly musculoskeletal: better muscle control and flexibility help the child handle or recover from dyskinesia attacks and maintain independence. ScienceDirect+2ncbi.nlm.nih.gov+2

Occupational therapy for daily living skills
Occupational therapists help the child practice dressing, writing, using utensils, and other daily tasks. They can suggest special grips, keyboards, or seating to work around movement episodes. This therapy does not change the brain’s glucose transport, but it builds new, more efficient ways to do tasks, which reduces fatigue and frustration and improves school performance and self-esteem. ScienceDirect+2ncbi.nlm.nih.gov+2

Speech-language therapy
Some children with GLUT1DS2 may have mild speech or language delay, or their speech may be affected during or after attacks. A speech-language therapist can work on clear articulation, understanding and using language, and social communication. Early therapy supports better school learning and social relationships. The mechanism is guided brain training: repeated, structured practice helps the brain build stronger language networks even if energy supply is limited. ScienceDirect+2ncbi.nlm.nih.gov+2

Cognitive and educational support
Learning problems can occur, especially attention and processing speed issues. Neuropsychological testing shows strengths and weaknesses, and teachers can adapt the classroom with extra time, quiet test rooms, or smaller chunks of work. The purpose is to match the teaching load to the child’s real brain energy capacity. This reduces failure and stress and allows the child to reach their potential. ncbi.nlm.nih.gov+2ScienceDirect+2

Psychological counseling and family support
Chronic rare disease can cause anxiety, low mood, and stress in both the child and parents. Counseling offers a safe place to talk about fears and learn coping skills. For parents, support groups for GLUT1 deficiency families can reduce isolation and share practical tips about diets and school issues. This emotional support does not change GLUT1, but it strongly protects mental health and family resilience. GLUT1 Deficiency Foundation+2ScienceDirect+2

Sleep hygiene program
Poor sleep can worsen seizures, dyskinesia, mood, and attention. A simple sleep plan includes regular bedtimes, calming routines, dark and quiet bedrooms, and avoiding screens late at night. For a child with GLUT1DS2, better sleep means the brain starts each day with a little more energy reserve, which may reduce trigger sensitivity. ScienceDirect+2ncbi.nlm.nih.gov+2

Trigger diary and self-monitoring
Keeping a diary of exercise type, food intake, stress, sleep, and attacks helps identify personal triggers. Over time, patterns may appear, such as attacks after long runs or missed snacks. The family and doctor can then adjust diet or exercise plans. The mechanism is behavioral: knowledge about triggers allows smarter prevention, even without changing the underlying gene. MalaCards+2ncbi.nlm.nih.gov+2

School health and emergency action plan
Schools should have a written plan describing what a movement attack looks like, what staff should do, when to call parents, and when to call emergency services. Teachers should know about the special diet and timing of meals. This planning reduces fear and ensures a quick, calm response, which often shortens or softens attacks and keeps the child safe. GLUT1 Deficiency Foundation+2ncbi.nlm.nih.gov+2

Caregiver training in safe handling during attacks
Parents, siblings, and other caregivers can be taught how to protect the child during sudden abnormal movements: clear space around them, support the head, and avoid forceful restraint. For some children, gentle stretching and calm reassurance help the episode pass. Safe handling prevents injuries such as falls or joint strain, which are common risks in paroxysmal movement disorders. MalaCards+2ScienceDirect+2

Genetic counseling for the family
Because GLUT1DS2 is usually autosomal dominant, each child of an affected person has about a 50% chance to inherit the mutation. Genetic counseling explains this risk in simple terms, discusses future pregnancies, and helps relatives decide whether to test. Knowing the pattern helps families make informed decisions and may lead to earlier diagnosis in future children. MalaCards+2ncbi.nlm.nih.gov+2

Avoidance of medicines that clash with ketogenic diets
Some medicines contain sugar (for example, some syrups) or may increase the risk of metabolic side effects or kidney stones when mixed with ketogenic diets. The care team usually reviews all drugs and, when possible, switches to sugar-free or safer options. This keeps ketone levels stable and lowers side-effect risk, so the diet can work at full strength. GLUT1 Deficiency Foundation+1

Protective equipment and safe environment
If attacks cause falls or sudden leg buckling, helmets, knee pads, or home safety changes (removing sharp corners, using non-slip mats) can be helpful. This does not treat the disease but protects the child from head injury and fractures. A safer environment allows the child to stay active, which is important for bone and muscle health. MalaCards+2ScienceDirect+2

Regular follow-up in a multidisciplinary clinic
Children with GLUT1DS2 benefit from regular visits with a team including a pediatric neurologist, metabolic dietitian, physiotherapist, psychologist, and social worker. At each visit, they check seizure control, dyskinesia frequency, growth, blood tests, and school progress. Slow, steady adjustments to diet and therapies over time usually give better long-term outcomes. ncbi.nlm.nih.gov+2Wiley Online Library+2

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Drug treatments

There is no drug that cures GLUT1 deficiency syndrome 2. Medicines are used to treat seizures or movement problems that happen in this condition. All dosing must follow FDA labels and be adjusted by a pediatric neurologist. ncbi.nlm.nih.gov+1

Levetiracetam (KEPPRA, SPRITAM – anti-seizure medicine)
Levetiracetam is a broad-spectrum anti-seizure drug often used in children. FDA labels show it is used for partial-onset, myoclonic, and primary generalized tonic-clonic seizures, with doses usually based on body weight and given twice daily. FDA Access Data+3FDA Access Data+3FDA Access Data+3 In a child with GLUT1DS2 and co-existing epilepsy, doctors may choose levetiracetam because it does not directly interfere with ketogenic diets and has relatively few drug interactions. Common side effects include sleepiness, irritability, and sometimes mood changes. Families should never change the dose without medical advice. FDA Access Data+2FDA Access Data+2

Topiramate (TOPAMAX, TROKENDI XR – anti-seizure and migraine medicine)
Topiramate is approved for many seizure types and for migraine prevention. It can also help with certain movement disorders by stabilizing brain excitation. FDA labels describe starting with a low dose and slowly increasing, with doses usually divided twice daily (or once daily for extended-release forms). FDA Access Data+2FDA Access Data+2 In GLUT1DS2, topiramate may be chosen if absence seizures or generalized seizures are present. Important side effects include weight loss, tingling, kidney stones, and trouble concentrating. Adequate fluids and kidney monitoring are essential, especially with ketogenic diets. FDA Access Data+2FDA Access Data+2

Clobazam (ONFI – benzodiazepine anti-seizure medicine)
Clobazam is a benzodiazepine used mainly for Lennox-Gastaut syndrome but also for other difficult seizures. FDA labeling recommends weight-based dosing, usually twice daily, with careful slow titration. FDA Access Data+2FDA Access Data+2 In a child with GLUT1DS2 and refractory seizures, clobazam may be added to other drugs. It enhances the calming GABA system in the brain. Side effects include sleepiness, drooling, behavior changes, and dependence with long-term use. Doctors must consider interactions with other sedating medicines and the ketogenic diet plan. FDA Access Data+1

Ethosuximide (absence seizure medicine)
Ethosuximide is a classic first-line drug for typical childhood absence epilepsy. It works by blocking T-type calcium channels in thalamic neurons, which are important in absence seizure circuits. In GLUT1DS2, where childhood absence epilepsy can appear, ethosuximide may be used to reduce staring spells. Dose is usually mg/kg/day divided twice, adjusted slowly. Common side effects include stomach upset, sleep problems, and rare blood count changes, so periodic blood tests are needed. ncbi.nlm.nih.gov+2ncbi.nlm.nih.gov+2

Valproic acid / divalproex sodium
Valproate is a broad anti-seizure drug effective for absence, myoclonic, and generalized tonic-clonic seizures. It increases GABA and affects sodium and calcium channels. In theory it can help epilepsy in GLUT1DS2, but it can increase weight and interact with mitochondrial function and the ketogenic diet, so specialists use it carefully. Typical pediatric doses are mg/kg/day in divided doses. Side effects include liver toxicity, pancreatitis, weight gain, hair loss, and birth-defect risk, so strong monitoring is required. ncbi.nlm.nih.gov+2Wiley Online Library+2

Lamotrigine
Lamotrigine is often used for generalized and focal seizures and can also improve mood stability. It blocks sodium channels and reduces glutamate release. In GLUT1DS2 with absence seizures, lamotrigine may be combined with other drugs when ethosuximide alone is not enough. Doses are increased very slowly to reduce the risk of serious rash (Stevens–Johnson syndrome). Side effects include rash, dizziness, and insomnia. ncbi.nlm.nih.gov+2ScienceDirect+2

Clonazepam
Clonazepam is a benzodiazepine often used for myoclonic seizures and certain movement disorders. It boosts GABA activity, calming overactive brain circuits. In GLUT1DS2, it can sometimes lessen severity of dyskinesia during an attack. Dosing is started very low and carefully increased because of drowsiness, drooling, and risk of tolerance and withdrawal seizures if stopped suddenly. ScienceDirect+2ncbi.nlm.nih.gov+2

Baclofen
Baclofen is a GABA-B agonist medicine commonly used to reduce spasticity (stiff muscles). In paroxysmal dyskinesias, some doctors try oral baclofen to calm dystonic postures, especially in the legs. It reduces excitatory neurotransmission in the spinal cord. Side effects include drowsiness, weakness, and dizziness. Sudden withdrawal of high doses can cause serious symptoms, so any change must be slow and supervised. MalaCards+2ScienceDirect+2

Trihexyphenidyl
Trihexyphenidyl is an anticholinergic drug used in dystonia and Parkinson’s disease. It can reduce abnormal involuntary movements by lowering acetylcholine activity in motor pathways. In some paroxysmal dyskinesia conditions, low doses help reduce frequency or intensity of attacks. Side effects include dry mouth, constipation, blurred vision, and confusion, especially at higher doses, so careful dose adjustment is vital. MalaCards+2ScienceDirect+2

Levodopa/carbidopa (for dopa-responsive dystonia-like features)
Some movement disorders that look similar to GLUT1DS2 are strongly responsive to levodopa. In selected GLUT1-spectrum patients with dystonia, doctors may try a cautious trial of low-dose levodopa/carbidopa. It increases dopamine in the brain and can sometimes improve gait and posture. However, in classic GLUT1DS2, benefit may be limited, and long-term use can cause dyskinesias, nausea, and low blood pressure. MalaCards+2ncbi.nlm.nih.gov+2

(Other drugs sometimes used for associated symptoms – such as carbamazepine, oxcarbazepine, zonisamide, or gabapentin – must be chosen individually and balanced with diet and side-effect risks. There is no single “best” drug; choice is case-by-case.) ncbi.nlm.nih.gov+2ScienceDirect+2

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Dietary molecular supplements

Medium-chain triglyceride (MCT) oil
MCT oil is often used as part of MCT or modified ketogenic diets. It is quickly absorbed and turned into ketones by the liver, giving extra brain fuel when glucose is low. A dietitian slowly increases the dose to avoid diarrhea or cramps and fits the total fat balance of the child’s meal plan. ScienceDirect+2kanso.com+2

Omega-3 fatty acids (DHA/EPA)
Omega-3 fats, found in fish oil, may support brain cell membranes and anti-inflammatory pathways. In some epilepsy and developmental disorders, they are studied as add-on therapy. For a child with GLUT1DS2 on a high-fat diet, omega-3-rich fats can be chosen instead of less healthy saturated fats, under dietitian guidance. Typical doses are weight-based and must not exceed safe levels. ScienceDirect+2Wiley Online Library+2

Multivitamin with minerals
Strict ketogenic or modified diets can be low in certain vitamins and minerals. A sugar-free multivitamin fills these gaps and helps prevent anemia, bone weakness, and immune problems. The dose usually follows age-based daily recommended intake. This does not treat GLUT1 directly but protects overall health so the child can tolerate long-term dietary therapy. maedica.ro+2Wiley Online Library+2

Calcium and vitamin D
Children on long-term ketogenic diets can have reduced bone mineral density. Calcium and vitamin D supplements support bone growth and reduce fracture risk. Doses are chosen based on diet content and blood tests. The mechanism is simple: these nutrients are the building blocks and regulators of healthy bone tissue. maedica.ro+2Wiley Online Library+2

Selenium and zinc (if deficient)
Some ketogenic diet studies report low selenium and zinc, which can lead to heart or immune problems if severe. Blood tests guide whether these minerals should be supplemented, usually in very small, carefully measured doses. Correcting deficiencies supports enzyme function and antioxidant defenses, helping the body cope with chronic disease stress. maedica.ro+2Wiley Online Library+2

Carnitine
Carnitine helps move fatty acids into mitochondria for energy production. In children with high-fat diets or on certain anti-seizure medicines, carnitine levels may drop. Supplementing carnitine in deficient children can reduce fatigue and muscle pain and improve tolerance of ketogenic diet. Dose depends on weight and blood levels and must be supervised. maedica.ro+2Wiley Online Library+2

Probiotics
Probiotics are beneficial bacteria that support gut health. High-fat, low-fiber diets sometimes lead to constipation and gut discomfort. Probiotics may improve bowel habits and indirectly support the immune system. Only sugar-free, diet-compatible products should be used, and they are chosen carefully in children with serious illness. ScienceDirect+2MDPI+2

Fiber supplements (psyllium, inulin – as allowed by diet)
Low-carb diets can be low in natural fiber. Sugar-free fiber supplements help prevent constipation and support healthy gut bacteria. The dose is increased slowly with fluids to avoid bloating. Better bowel function improves comfort, sleep, and appetite, which all help overall disease management. maedica.ro+2Wiley Online Library+2

Electrolyte supplements (as needed)
If blood tests show low sodium, potassium, magnesium, or bicarbonate, a doctor may prescribe specific electrolyte supplements. This is especially important when a child is on topiramate or a strict ketogenic diet, which can shift acid–base balance. Correcting electrolytes prevents fatigue, cramps, and some types of arrhythmia. FDA Access Data+2FDA Access Data+2

Folate and B-vitamins (if low)
Some anti-seizure drugs and restrictive diets can lower folate and other B-vitamin levels, which are important for blood cells and brain function. Supplements, when indicated by blood tests, help maintain normal homocysteine, reduce anemia risk, and support cognitive function. Doses follow age-specific recommendations. ScienceDirect+2Wiley Online Library+2

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Immune-supporting and regenerative / stem-cell-related drugs

No approved stem cell or gene therapy yet
At present, there is no FDA-approved stem cell drug, gene therapy, or regenerative medicine that directly treats GLUT1 deficiency syndrome 2. Research is exploring ways to correct SLC2A1 gene defects or improve GLUT1 function, but these treatments remain experimental and are not standard care. Families should be very careful about unproven “stem cell” offers. Nature+2Wiley Online Library+2

Routine childhood vaccinations
Standard vaccines (such as measles, polio, tetanus, and others) are very important for children with GLUT1DS2. Infections put extra stress on the brain and can trigger more seizures or dyskinesia. Vaccines work by training the immune system to recognize germs before they cause severe disease. They are not disease-specific drugs but are key immune protectors. GLUT1 Deficiency Foundation+2ScienceDirect+2

Vitamin D and general immune support
Vitamin D, when low, is linked to weak bones and sometimes higher infection risk. Correcting low vitamin D with supplements, as guided by blood tests, helps bones and may support normal immune function. It is not unique to GLUT1DS2 but is an important part of whole-body care in children on special diets. maedica.ro+2Wiley Online Library+2

Balanced nutrition with adequate protein
Good immunity needs enough calories and protein. A well-designed ketogenic or modified diet still provides sufficient protein for growth and immune cells. Dietitians carefully calculate protein targets based on age and weight. This is not a “drug,” but it is as important as any medicine in keeping the child resistant to infections. GLUT1 Deficiency Foundation+2maedica.ro+2

Careful use of immunosuppressive drugs
If a child with GLUT1DS2 ever needs steroids or other immune-suppressing medicines for different diseases, the team will adjust diet and seizure medicines to keep the brain as stable as possible. There is no immunosuppressive drug used to treat GLUT1DS2 itself, and such drugs are usually avoided unless absolutely necessary for another condition. ScienceDirect+2Wiley Online Library+2

Future gene-targeted therapies (research only)
Scientists are exploring gene therapy, small molecules that boost GLUT1 function, and other innovative methods to correct transport defects. These are in early research phases, often in cells or animal models, and not ready for routine clinical use. Families can ask specialists about clinical trials but should understand that safety and benefit are still being studied. Nature+2MDPI+2

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Surgeries and procedures

Vagus nerve stimulation (VNS)
VNS is a small device implanted under the skin in the chest with a wire wrapped around the vagus nerve in the neck. It sends regular gentle electrical pulses to brain circuits to reduce seizure frequency. It is considered only when seizures remain severe despite medicines and diet. In GLUT1DS2, where diet is first-line, VNS is rare but may be discussed in very difficult cases. ncbi.nlm.nih.gov+1

Epilepsy surgery (resective)
If a child with GLUT1DS2 has seizures that come clearly from one small brain area (focal epilepsy) and do not respond to diet and medicines, epilepsy surgeons may consider removing that focus. This is uncommon in GLUT1DS2 because seizures are often more generalized. The purpose is to give better seizure control and protect development. Extensive testing is needed first. ncbi.nlm.nih.gov+2Wiley Online Library+2

Deep brain stimulation (DBS) for dystonia
In severe, disabling dystonia that does not respond to medicines, deep brain stimulation is sometimes used. Electrodes are placed in deep motor areas of the brain and connected to a chest battery. DBS modulates abnormal movement circuits. For GLUT1-related dystonia, DBS is experimental and reserved only for extreme cases in specialized centers. MalaCards+2ScienceDirect+2

Feeding tube placement (gastrostomy) in selected cases
If a child cannot safely eat enough to maintain a precise ketogenic ratio by mouth, a feeding tube into the stomach may be considered. This allows accurate delivery of special formulas and medications. The goal is not to treat the gene defect but to make long-term diet therapy possible and safe. maedica.ro+2Wiley Online Library+2

Orthopedic procedures for contractures
Long-standing dystonia can cause fixed joint contractures or hip problems. In rare severe situations, orthopedic surgery may release tight tendons or correct deformities to improve walking and sitting. Intensive physiotherapy follows. These procedures do not treat GLUT1DS2 itself but reduce pain and disability from secondary musculoskeletal changes. ScienceDirect+2UniProt+2

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Prevention and lifestyle protection

You cannot prevent the genetic change that causes GLUT1 deficiency syndrome 2. But you can prevent or reduce many complications: early diagnosis, early diet therapy, safe exercise, and careful infection control all help. MalaCards+2GLUT1 Deficiency Foundation+2

1. Early recognition of movement attacks and absence seizures and quick referral to a pediatric neurologist. ncbi.nlm.nih.gov+2ncbi.nlm.nih.gov+2

2. Early lumbar puncture and genetic testing when GLUT1 deficiency is suspected, so treatment can start while the brain is still developing. ncbi.nlm.nih.gov+2University of Chicago Genetic Services+2

3. Starting a medical ketogenic diet as soon as safely possible when diagnosis is confirmed, under expert guidance. maedica.ro+2ScienceDirect+2

4. Keeping strict follow-up visits to adjust diet and medicines over time. Wiley Online Library+2ncbi.nlm.nih.gov+2

5. Avoiding long fasting, especially before exercise or illness. MalaCards+2ncbi.nlm.nih.gov+2

6. Quickly treating fevers and infections to reduce stress on the brain. GLUT1 Deficiency Foundation+2ScienceDirect+2

7. Keeping vaccinations up to date. GLUT1 Deficiency Foundation+2MDPI+2

8. Providing safe sports choices with proper rest and hydration. MalaCards+2ScienceDirect+2

9. Protecting the head and body during attacks to prevent injuries. MalaCards+2UniProt+2

10. Offering strong psychological and educational support to prevent secondary depression, anxiety, and academic failure. ScienceDirect+2GLUT1 Deficiency Foundation+2

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When to see doctors

Parents should keep regular appointments with the child’s pediatric neurologist, metabolic dietitian, and other team members. You should seek urgent or emergency medical care if:

• Movement attacks suddenly become much longer, more painful, or more frequent. MalaCards+2ncbi.nlm.nih.gov+2

• The child has a new seizure type, long seizures, or clusters of seizures.

• The child cannot drink or eat, is vomiting, or shows signs of dehydration while on a ketogenic diet. maedica.ro+2Wiley Online Library+2

• There is confusion, trouble waking up, severe headache, or repeated falls. ScienceDirect+2Wikipedia+2

• There are signs of serious drug side effects, such as yellow skin or eyes, extreme sleepiness, rash, or breathing problems. FDA Access Data+2FDA Access Data+2

Regular check-ups are also needed to watch growth, blood lipids, liver function, kidneys, and bone health while on specialized diets and medicines. maedica.ro+2Wiley Online Library+2

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What to eat and what to avoid

For GLUT1DS2, food choices are not the same for every child. A specialist sets an exact plan. These are general ideas only: maedica.ro+2ScienceDirect+2

Often recommended (if they fit the ketogenic plan):

1. High-fat foods like oils, butter, cream, and ketogenic formulas, weighed exactly as prescribed.

2. Fatty fish, eggs, and meats in portions set by the dietitian.

3. Low-carbohydrate, non-starchy vegetables (for example, small portions of leafy greens) measured carefully.

4. Sugar-free, carbohydrate-free fluids such as water and allowed electrolyte drinks.

5. Sugar-free medicines and supplements only. maedica.ro+2GLUT1 Deficiency Foundation+2

Commonly avoided or tightly limited:

1.  Regular sugar, sweets, juices, and sweetened drinks.
2. Bread, rice, potatoes, pasta, and most cereals.
3. Hidden sugars in syrups, chewing gum, and processed foods.
4. Very high-protein diets that push fat ratio too low.
5. Health” products that claim to boost the brain but contain a lot of carbohydrates or are not tested in ketogenic diets. Wikipedia+2maedica.ro+2

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Frequently asked questions

1. Is childhood onset GLUT1 deficiency syndrome 2 the same as classic GLUT1 deficiency?
They are part of the same disease family but not exactly the same. GLUT1DS2 usually presents mainly with exercise-triggered abnormal movements (paroxysmal dyskinesia), sometimes with absence seizures and mild learning problems, while classic GLUT1 deficiency often starts with early infantile seizures and more global delays. Both are caused by SLC2A1 gene variants that reduce glucose transport into the brain. MalaCards+2ncbi.nlm.nih.gov+2

2. How common is this condition?
GLUT1 deficiency in general is rare, with estimated birth incidence between about 1 in 24,000 and 1 in 90,000. GLUT1DS2 is a smaller subset within this group, so it is even rarer. Many cases are probably still missed or diagnosed late because symptoms can look like more common movement or epilepsy disorders. Wikipedia+2MalaCards+2

3. Does every child with GLUT1DS2 need a ketogenic diet?
Most experts recommend some form of medical ketogenic diet for nearly all patients with GLUT1 deficiency, including GLUT1DS2, unless there is a strong reason not to. The diet is considered the main treatment because it gives the brain an alternative fuel. However, the exact type of diet and ratio is personalized, and a few patients may not respond or tolerate it well. Wiley Online Library+3ScienceDirect+3maedica.ro+3

4. Will diet alone stop all movement attacks and seizures?
Diet often greatly reduces attacks and seizures, but it may not remove them fully. Some children still need anti-seizure or movement medicines as add-ons. Over time, attacks can change with age, hormones, and stress, so the management plan also changes. ScienceDirect+2GLUT1 Deficiency Foundation+2

5. Can a child live a normal life with GLUT1DS2?
With early diagnosis, good dietary control, and strong therapy support, many children can walk, talk, attend school, and enjoy family life. They may still have certain limits, for example with long intense exercise or late-night activities. How “normal” life is depends on severity, how early treatment began, and individual response. MalaCards+2ScienceDirect+2

6. Is this condition always inherited?
GLUT1DS2 is usually autosomal dominant, meaning one changed gene copy is enough to cause disease. Sometimes the mutation appears for the first time in the child (a de novo mutation), and sometimes it is inherited from a mildly affected parent. Genetic counseling can explain the pattern for each family. MalaCards+2ncbi.nlm.nih.gov+2

7. Can GLUT1 deficiency syndrome 2 be cured?
At present, there is no cure that completely fixes the gene or the GLUT1 transporter. Treatment focuses on giving the brain alternative fuel, controlling seizures and movements, and supporting development. Research on gene-based therapies and new metabolic treatments is ongoing. Nature+2Wiley Online Library+2

8. Does puberty or adulthood change the symptoms?
Yes. In many people with GLUT1 deficiency, seizures may improve with age, while movement problems and migraines can become more prominent. For GLUT1DS2, exercise-induced dyskinesia may continue into adulthood, but some people learn to manage triggers better. Treatment plans are re-evaluated at transitions such as puberty. ScienceDirect+2MalaCards+2

9. Can ordinary sports be dangerous?
Light to moderate sports with good rest and hydration are usually safe and healthy. Very long, intense exercise without breaks may trigger attacks. The care team often suggests trial-and-error planning: start with shorter activities, keep snacks or ketone-compatible drinks, and slowly increase as tolerated. Safety equipment and supervision are important. MalaCards+2ScienceDirect+2

10. Are there special school rights for children with GLUT1DS2?
Many countries allow individualized education plans for children with chronic neurological disorders. These can include extra test time, breaks, diet support at school, and safety plans during attacks. Parents can talk with doctors and school staff to document needs and arrange support. GLUT1 Deficiency Foundation+2ncbi.nlm.nih.gov+2

11. Will my child’s IQ always be low?
Not necessarily. The spectrum is wide. Some people with GLUT1DS2 have near-normal or normal intellect but still have movement attacks. Others have mild learning disabilities. Early and strong treatment (diet, therapies, and education support) gives the best chance for good cognitive outcomes. ScienceDirect+2MalaCards+2

12. Can pregnancy be safe for women with GLUT1 deficiency?
With careful planning, many women with GLUT1 deficiency can have successful pregnancies. They need very close monitoring of diet, seizures, and medicines with high-risk obstetric and neurology teams. Some anti-seizure drugs carry higher risk of birth defects, so choices must be reviewed before conception. ncbi.nlm.nih.gov+2Wiley Online Library+2

13. Does caffeine or energy drinks help or harm?
Energy drinks and many colas contain sugar and caffeine. For someone on a ketogenic or low-carb diet, the sugar content alone is usually a problem. Caffeine can also disturb sleep and trigger anxiety or palpitations. Most specialists advise avoiding energy drinks and using only carefully planned, sugar-free beverages. Wikipedia+2maedica.ro+2

14. Should families join patient organizations?
Yes, joining GLUT1 deficiency foundations or rare disease groups connects families with updated information, practical tips, and emotional support. These groups also push forward research and awareness, which can bring better treatments in the future. GLUT1 Deficiency Foundation+1

15. What is the single most important step after diagnosis?
The most important step is to quickly set up care with an experienced pediatric neurologist and metabolic dietitian and start the most suitable ketogenic therapy. At the same time, parents should learn about the condition in simple language, keep a symptom diary, and build a support network. Early, informed action can change the child’s long-term path in a very positive way. Wiley Online Library+3ScienceDirect+3maedica.ro+3

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December 31, 2025.