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A genetic condition that can cause epilepsy-Glut1 Deficiency explained by Dr. Firas Taha: Feature Article

Over the next few issues of our newsletter, we will be highlighting certain genetic conditions that affect the brain and can often lead to seizures.  Although these conditions are considered rare, it is important for this information to be disseminated to the general public to ensure that anyone afflicted with these has awareness of their existence. In this issue, we are focusing on Glucose transporter type 1 (Glut1) deficiency syndrome.  We sat down with Dr. Firas Taha, pediatric epileptologist at the Northeast Regional Epilepsy Group and asked him to explain this complex disorder to us.  Dr. Taha completed his child neurology residency at the Mayo Clinic Florida and his clinical neurophysiology fellowship at the New York University, New York, NY.  He is board certified in: the American Board of Psychiatry and Neurology - Neurology with Special Qualification in Child Neurology and the American Board of Psychiatry and Neurology - Clinical Neurophysiology. He now treats pediatric patients in Jersey City, Morristown, and Hackensack, New Jersey. 

Could you explain to us as plainly as possible, what is Glut1 Deficiency?

Glut1 Deficiency is a rare genetic condition that affects brain metabolism. Other names for the condition include De Vivo disease, glucose transport defect, glucose transporter type 1 deficiency syndrome, and Glut1 DS, among others. It is caused by a mutation in the SLC2A1 gene, which regulates the glucose transporter protein type 1, which is the main transporter of glucose into the brain. Glucose is the body's and the brain's primary source of energy.  When glucose transport is impaired by a mutation in the glucose transporter gene, it creates an energy crisis because the brain is not able to utilize its favorite fuel. 

This inability to properly use glucose in the brain of patients with Glut1 Deficiency causes neurological symptoms including seizures, abnormal movement, problems with coordination, and developmental delays.  The classic presentation was thought to involve seizures that began in infancy, delayed neurologic development, microcephaly (smaller head), and complex movement disorders, but now a much broader spectrum of symptoms is recognized. 

How common is Glut1 Deficiency?

Glut1 deficiency syndrome is a rare disorder, and the exact prevalence is unknown. Hundreds of patients have been diagnosed worldwide. Researchers suggest that the disorder may be under-diagnosed, as many neurological disorders present with similar symptoms. Mutations in the SLC2A1 gene have been found in many patients with other diagnosed epilepsies and ataxias, which suggests that some patients with these conditions may also have undiagnosed Glut-1 deficiency. 

What kind of seizures can be caused by Glut 1 deficiency?

The seizures in the classic early onset Glut1 deficiency usually begin between age one and six months, and can be the first indication of brain dysfunction. The seizures in infancy are usually focal seizures, which can appear first as breath holding spells or abnormal eye movements, and may include complex absence and atonic seizures among others. As the child ages and the brain matures, different types of generalized seizures become more common. The frequency and type of seizures varies among individuals with Glut 1 deficiency, and numerous types of seizures may occur, including myoclonic, atonic, focal, and generalized tonic-clonic seizures.  We also know that 10% - 15% of patients who have been diagnosed with Glut1 deficiency have never had a clinical seizure so far. 

As mentioned above, the spectrum of clinical presentations for Glut1 deficiency has now been found to be broader than previously known, with several types of movement disorders and epilepsies now having been found to be associated with Glut1 deficiency. 10% of early onset absence seizures and 5% of Myoclonic Astatic Epilepsy (Doose Syndrome) are caused by Glut1 deficiency. It is estimated that Glut1 deficiency causes 1% of cases of idiopathic generalized epilepsy.

What are the other signs and symptoms of Glut1 Deficiency?

Aside from epilepsy, the neurological symptoms of Glut1 Deficiency primarily involve cognition, behavior and movement. Cognitive symptoms affect intelligence and can range from subtle learning difficulties to severe intellectual disability. Speech and language delay, problems with focus, attention difficulties and hyperactivity can be present; as can difficulties with social interaction. In terms of motor problems, these can be quite varied. Many patients have spasticity, which is a stiffness of the muscles which causes difficulty with movement.  Patients may display ataxia, (difficulty coordinating movements), involuntary movements called chorea and dystonia, and/or speech difficulties (dysarthria). These symptoms may be constant, or fluctuate throughout the day. Some patients experience episodes of confusion, lack of energy, headaches, or muscle twitches, particularly during periods of fasting.

How is Glut1 Deficiency Diagnosed?

When Glut1 Deficiency is suspected by your doctor, a lumbar puncture (spinal tap) should be performed as the first step. If the glucose concentration in the spinal fluid is low, the recommended diagnostic protocol is to follow up with genetic testing to confirm a genetic mutation in the SLC2A1 gene.  Glucose transport can also be analyzed in the red blood cells, as the protein is identical to that found in the brain. 10-15% of patients do not have a detectable gene mutation but receive a diagnosis based on their symptoms and a positive lumbar puncture. 

How is Glut1 Deficiency Treated?

Although there is no cure for Glut1 Deficiency, there is an effective treatment. The Ketogenic Diet is a specialized high fat low carbohydrate diet which is currently the core of this treatment. Anti-seizure medications are generally not as effective, since they do not provide nourishment to the starved brain. As Glut1 Deficiency is essentially an inability for the brain to utilize its preferred fuel (glucose), this diet allows the brain to use an alternate source of energy called ketone bodies as fuel. Early diagnosis and treatment is the key to protecting brain growth and function during development. The Ketogenic Diet improves many of the symptoms associated with Glut1 Deficiency, but must be carefully crafted and tailored to meet the needs of each patient and should only be used under the care of medical professionals. 

Can clinicians in NEREG diagnose and treat Glut1 Deficiency?

Yes. The Northeast Regional Epilepsy Group is well-equipped to diagnose and provide treatment for patients with Glut1 Deficiency. We have a team of pediatric epileptologists (neurologists who have completed training in epilepsy and pediatrics) who are experienced in both medication based and non-medication based treatment of epilepsy. If Glut1 Deficiency is suspected clinically, our team has access to the latest advances in medical diagnostics, including specialized genetic testing such as indicated for patients with Glut1 Deficiency. Many of our patients with medication-refractory epilepsy are currently pursuing the Ketogenic Diet through our NEREG physicians and registered dieticians at two separate centers. Patients with Glut1 Deficiency may also benefit from an evaluation by our neuropsychologists, whose assessments and recommendations can help families and schools address their child's unique learning issues, educational and therapy goals.

Could you point our readers to foundations dedicated to helping patients with Glut1 Deficiency and their caregivers?   

The Glut1 Deficiency Foundation is a volunteer, non-profit family organization dedicated to educating others about Glut1 Deficiency, and supporting and funding researchers as they work towards a cure. They have created an excellent forum for sharing support and resources and information between families, patients, and healthcare professionals. They organize conferences around the US and offer research grants to scientists.

Glut1 Deficiency Foundation:

Thank you so much, Dr. Taha, for sitting down and explaining this to us in plain English. We hope this will reach families in need and provide guidance.  


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