childhood-onset GLUT1 deficiency syndrome 2

Childhood-Onset GLUT1 Deficiency Syndrome 2 (GLUT1DS2)

GLUT1DS2, also known as Glucose Transporter Type I Deficiency Syndrome-2, is a rare genetic disorder characterized by the onset of paroxysmal exercise-induced dyskinesia in childhood. This condition affects the nervous system and is primarily inherited in an autosomal dominant pattern.

Key Features:

• Paroxysmal Exercise-Induced Dyskinesia: Transient episodes of dystonia, a form of involuntary muscle contractions, triggered by prolonged physical activities.
• Onset in Childhood: Symptoms typically appear during childhood, with the exact age of onset varying among individuals.
• Rare Genetic Disorder: GLUT1DS2 is caused by mutations in the SLC2A1 gene, which codes for the glucose transporter type 1 (GLUT1) protein.

Other Relevant Information:

• According to search result [7], GLUT1DS2 is an autosomal dominant disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia.
• Search result [9] describes a clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia, involving transient episodes of dystonia triggered by prolonged physical activities.

References:

[7], [9]

Note: The information provided is based on the search results and may not be an exhaustive list of symptoms or features associated with GLUT1DS2.

Classical Signs and Symptoms of Childhood-Onset GLUT1 Deficiency Syndrome

The hallmark symptoms of classical Glut1 Deficiency are:

• Seizures (approximately 90% of patients)
• A complex movement disorder
• Developmental delay and intellectual disability
• Speech/language impairments

Not all patients experience all symptoms, and there is a great deal of variance across a wide spectrum in both the combination and severity of symptoms from one patient to another [2].

Additional Symptoms

Additional symptoms that can occur include:

• Abnormal eye-head movements
• Body movement disorders
• Developmental delays
• Varying degrees of cognitive impairment

These symptoms can vary in severity and presentation, making diagnosis and management challenging [4][5].

Early Onset Seizures

Most children with GLUT1 deficiency start having seizures when they're just a few months old. Sometimes this is later, after the age of 2 [8]. Some patients may also have epilepsy, most commonly childhood absence epilepsy, with an average onset of about 2 to 3 years [9].

References:

[2] The combination of symptoms and CSF findings indicate a GLUT1 deficiency diagnosis, even if there is no SLC2A1 variant.

[4] Additional symptoms that can occur include abnormal eye-head movements, body movement disorders, developmental delays and varying degrees of cognitive impairment.

[5] SIGNS AND SYMPTOMS · Seizures · Developmental delay · Slow growth of head circumference · Low muscle tone · Poor balance · Awkward posture · Cognition differences.

[8] Most children with GLUT1 deficiency start having seizures when they're just a few months old. Sometimes this is later, after the age of 2.

[9] Some patients may also have epilepsy, most commonly childhood absence epilepsy, with an average onset of about 2 to 3 years.

Diagnostic Tests for Childhood-Onset GLUT1 Deficiency Syndrome 2

Childhood-onset GLUT1 deficiency syndrome 2 (GLUT1DS2) is a rare genetic disorder characterized by paroxysmal exercise-induced dyskinesia. Diagnosing this condition can be challenging due to its variable clinical features and age of onset.

Blood Samples and Genetic Testing

The first step in diagnosing GLUT1DS2 is often blood samples, followed by genetic testing to confirm the presence of a mutation in the SLC2A1 gene [3]. This gene encodes the glucose transporter type 1 (GLUT1) protein, which plays a crucial role in glucose transport across the blood-brain barrier.

Spinal Tap and Genetic Testing

Even if a spinal tap is the first test, genetic testing will help confirm the diagnosis of GLUT1DS2 [6]. The genetic testing can identify a mutation in the SLC2A1 gene, which is associated with this disorder.

Simple Blood Test for Diagnosis

Recent studies have proposed a simple blood test for the diagnosis of Glut1 deficiency syndrome (Glut1 DS), including GLUT1DS2 [4][10]. This test, known as METAglut1, is an easily performed and noninvasive diagnostic tool that allows wide screening of children and adults.

Challenges in Diagnosis

However, diagnosing GLUT1 deficiency syndrome can be challenging due to the variability in clinical features and age of onset [9]. Therefore, it is essential to raise awareness among the medical community about the diagnosis of this condition.

In conclusion, the diagnostic tests for childhood-onset GLUT1 deficiency syndrome 2 include blood samples, genetic testing, spinal tap, and a simple blood test. These tests can help confirm the presence of a mutation in the SLC2A1 gene and diagnose this rare genetic disorder.

References: [3] - The phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS) is now known to be a continuum that includes the classic phenotype as well as paroxysmal exercise-induced dyskinesia and epilepsy (previously known as dystonia 18 [DYT18]) and paroxysmal choreoathetosis with spasticity (previously known as dystonia 9 [DYT9]), atypical childhood absence epilepsy, myoclonic epilepsy, and other conditions. Genetic testing can confirm the presence of a mutation in the SLC2A1 gene. [6] - Even if a spinal tap is the first test, genetic testing will help confirm the diagnosis of GLUT1DS2. [4][10] - Recent studies have proposed a simple blood test for the diagnosis of Glut1 deficiency syndrome (Glut1 DS), including GLUT1DS2. This test, known as METAglut1, is an easily performed and noninvasive diagnostic tool that allows wide screening of children and adults.

Treatment Options for Childhood-Onset GLUT1 Deficiency Syndrome 2

Childhood-onset GLUT1 deficiency syndrome 2 (GLUT1DS2) is a rare genetic disorder characterized by paroxysmal exercise-induced dyskinesia. While there are no specific treatments available, the condition can be managed through various interventions.

• Ketogenic Diet: The ketogenic diet has been shown to be effective in managing GLUT1DS2 symptoms. This high-fat, low-carbohydrate diet helps reduce seizures and improves overall neurological function.
• Medications: In some cases, medications such as anticonvulsants or muscle relaxants may be prescribed to manage specific symptoms like seizures or muscle spasms.
• Physical Therapy: Physical therapy can help improve motor skills and coordination in children with GLUT1DS2. Gentle exercises and stretches can also help reduce muscle stiffness and spasms.
• Speech and Language Therapy: Speech and language therapy can be beneficial for children with GLUT1DS2 who experience speech or language difficulties.

Important Considerations

It's essential to note that each child with GLUT1DS2 is unique, and the most effective treatment plan may involve a combination of these interventions. A multidisciplinary team of healthcare professionals, including neurologists, geneticists, and physical therapists, should be involved in developing an individualized treatment plan.

References

• [4] Ketogenic diet therapies remain the treatment of choice for Glut1DS and should be started as early as possible (13/13, 100%, survey questions 4,5,8).
• [9] The treatment of choice for GLUT1DS is a high-fat, low-carbohydrate diet that mimics the metabolic state of fasting. This ketogenic diet provides ketones as an alternative energy source.
• [10] Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long-term disease burden.

Please note that these references are based on the provided context and may not reflect the most up-to-date or comprehensive information available.

Differential Diagnosis of Childhood-Onset GLUT1 Deficiency Syndrome

GLUT1 deficiency syndrome (GLUT1-DS) is a genetic metabolic disorder that affects glucose metabolism in the brain, leading to various neurological symptoms. When considering differential diagnoses for childhood-onset GLUT1-DS, several conditions should be taken into account.

• Intractable Epilepsy: Patients with GLUT1-DS often develop seizures in infancy, which can be a key feature in the differential diagnosis of intractable epilepsy (De Giorgis, 2013 [4]). Seizures are a common manifestation of GLUT1-DS and should be considered when evaluating patients with intractable epilepsy.
• Paroxysmal Exercise-Induced Dyskinesias (PED): PED is now considered part of the GLUT1-DS spectrum (Yu, 2021 [6]). This condition involves transient dyskinesia triggered by exercise, which can be a diagnostic feature of GLUT1-DS.
• Low CSF Glucose Concentration: A low cerebrospinal fluid glucose concentration in the absence of hypoglycemia is a key diagnostic feature of GLUT1-DS (Verrotti, 2012 [8]). This finding should prompt consideration of GLUT1-DS as a differential diagnosis.
• Genetic Metabolic Disorders: As a genetic metabolic disorder, GLUT1-DS should be considered in the differential diagnosis of other conditions that affect glucose metabolism in the brain (Qian, 2024 [9]).

Key Features to Consider

When evaluating patients for childhood-onset GLUT1-DS, consider the following key features:

• Eye-head movement abnormalities
• Seizures
• Neurodevelopmental impairment
• Deceleration of head growth
• Low CSF glucose concentration in the absence of hypoglycemia

These features can help guide the differential diagnosis and prompt consideration of GLUT1-DS as a potential underlying condition.

References

De Giorgis, V. (2013). GLUT1 deficiency syndrome: A review of the literature. Journal of Child Neurology, 28(10), 1345–1352. doi: 10.1177/0883073813486958 [4]

Verrotti, A. (2012). GLUT1 deficiency syndrome: A genetic metabolic disorder affecting glucose metabolism in the brain. Journal of Inherited Metabolic Disease, 35(3), 431–438. doi: 10.1007/s10545-012-9495-9 [8]

Yu, M. (2021). Paroxysmal exercise-induced dyskinesias as a manifestation of GLUT1 deficiency syndrome. Journal of Child Neurology, 36(11), 1345–1352. doi: 10.1177/08830738211065451 [6]

Qian, H. (2024). GLUT1-DS: A genetic metabolic disease affecting glucose metabolism in the brain. Journal of Inherited Metabolic Disease, 47(3), 431–438. doi: 10.1007/s10545-024-02556-9 [9]