A Closer Look at GLUT1 Deficiency in Adulthood

Hello and welcome to Science with Sandra. Happy May!

For this blog edition, I would like to highlight a publication by Dr. Roba El Zibaoui, a postdoctoral Research Fellow in the Department of Neurology, Divisions of Epilepsy and Neuroimmunology at Johns Hopkins School of Medicine. In this publication, Dr. El Zibaoui is a co-author alongside Dr. Mackenzie Cervenka, Dr. Tanya McDonald, and Dr. Eric Kossoff, esteemed members of our community, as well as our beloved Executive Director, Glenna Steele. This was a follow up publication on learnings from a PCORI (Patient Centered Outcomes Research Institute) project on adult experiences in GLUT1 Deficiency.

The title of the publication is: “Clinical, practical, and psychosocial challenges of living with GLUT1 Deficiency Syndrome.”  

While much of the research in our community has focused on children, this study aimed to better understand what life is like for adults with GLUT1 Deficiency and their caregivers. For this study, the authors collaborated with the GLUT1 Deficiency Foundation to develop a survey addressing gaps in understanding the adult experience from both patient and caregiver perspectives. The questions focused on symptoms, treatments, daily life, and challenges.

Results

Demographics
 A total of 12 surveys completed by adult patients and 24 surveys completed by caregivers were analyzed.
 Fifty percent of participants in each group were female.

Key symptoms and challenges
 The study found that GLUT1 Deficiency affects individuals in many different ways, and symptoms can change over time.

• Seizures were the most common symptom. Interestingly, males were more likely to experience seizures and alternating hemiplegia and this finding warrants further validation in larger cohorts. Many participants also reported movement disorders, such as involuntary movements or difficulty walking, with females more frequently experiencing ataxia than males.
• Cognitive and speech difficulties were also reported.
• Caregivers identified heat as a common symptom trigger.
• Puberty was noted as a particularly challenging period, with some individuals experiencing worsening symptoms.

Ketogenic dietary therapy
The standard treatment for GLUT1 Deficiency is a ketogenic diet therapy, a high-fat, moderate-protein, low-carbohydrate diet that induces ketone production (an alternative fuel source to glucose). 

The survey showed that:

• Most participants had tried a ketogenic diet therapy, and many were still following it.
• Many reported improvements in seizures and neurobehavioral symptoms, particularly when ketone levels were between 2-4 mmol/L.
• There were no significant differences in symptoms between patients following two types of ketogenic diet therapy, the classical ketogenic diet and those on the Modified Atkins Diet, except for a higher rate of speech difficulties among those on the classical ketogenic diet, possibly reflecting a more severe disease in this group.
• Some individuals transitioned to less restrictive versions (such as the Modified Atkins Diet) due to dietary burden, limited symptom control, or the use of supplements, including coenzyme Q10 and CBD oil.

Medications and therapies
Many individuals reported using anti-seizure medications despite limited efficacy, along with other adjunctive treatments.  Carbidopa- was the most commonly used therapy for concomitant movement disorders, followed by baclofen, clonazepam, and stimulants for other comorbidities.

Supportive therapies such as physical, speech, occupational, and behavioral therapy were commonly used, particularly earlier in life.

Daily life and independence
The study highlighted variability in daily functioning:

• Most participants reported living with family members.
• Overall, respondents reported a good mood, quality of life, and access to financial and social support.
• Many had completed secondary or vocational education and were engaged in employment, including volunteer, part-time, and full-time work.
• Some adults demonstrated greater independence in activities of daily living, such as cooking, managing finances, or driving.
• Others reported mobility challenges requiring the use of assistive devices such as wheelchairs or walkers.

Despite these differences, the study indicates that individuals with GLUT1 Deficiency can lead meaningful and productive lives, especially with appropriate support.

Emotional and social impact
Living with GLUT1 Deficiency can also affect mental health.
In this survey, some patients reported depression. Notably, caregiver and patient reports differed, with fewer caregivers reporting depression in their loved ones compared to the reports made by patients themselves.

The authors suggest that caregivers may sometimes perceive patients as having limited awareness of their condition. They emphasize the importance of psychoeducational interventions for both patients and caregivers to improve disease understanding, support ketogenic diet therapy management, and enhance quality of life.

Major gaps and unmet needs
 The study identified several ongoing challenges:

• Delayed diagnosis: Some adults were diagnosed later in life, despite symptoms beginning in childhood.
• Difficult transition to adult care: Fewer than half of individuals in the caregiver-reported group successfully transitioned from pediatric to adult healthcare providers, including neurologists, dietitians, or specialized ketogenic centers.
• Barriers to continued treatment: Challenges with maintaining the ketogenic diet were reported, often due to inadequate transition planning and a lack of adult-focused ketogenic specialists and centers.

Conclusion
This study highlights that GLUT1 Deficiency is a complex condition with broad variability in symptoms. It underscores the ongoing medical, cognitive, and psychosocial challenges faced by individuals into adulthood and emphasizes the need for multidisciplinary, lifelong care.

Despite advances in research and care, improving awareness, expanding access to specialized services, and developing new therapies remain critical to enhancing outcomes and quality of life for individuals living with GLUT1 Deficiency and their families.

We thank the Johns Hopkins Adult Epilepsy Diet Center team and other collaborating team members that contributed to this publication, and important work and for their continuous support to our community! We also thank patients and caregivers for sharing their experience with GLUT1 Deficiency.

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