Dietary Therapy for GLUT1 Deficiency Syndrome

February 10, 2016
Veronica Hackethal, MD

When evaluating dietary therapy in patients with GLUT1 deficiency syndrome, did the ketogenic diet prove more effective than the alternatives?

Certain alternatives to the classic ketogenic diet may be just as good for controlling seizures and abnormal movements in the rare genetic disorder glucose-transporter 1 (GLUT1) deficiency syndrome, according to a study published online in the journal Seizure.1

“Of those that responded and are receiving dietary treatments, there was an overwhelmingly positive response for control of both seizures and abnormal movements. The majority of patients were able to achieve this success without the use of anticonvulsants and sustain this level of control for many years,” wrote senior author Eric Kossoff, MD, of the Johns Hopkins Hospital in Baltimore, MD, and colleagues.

The study is the largest to date to evaluate dietary therapy in patients with GLUT1 deficiency syndrome, which is difficult to study because of its rarity. 

Only about 500 cases of GLUT 1 deficiency syndrome have been identified worldwide since the disorder was first described in 1991.2 It is caused by a dominant mutation that results in reduced glucose accumulation in the brain, causing encephalopathy. Symptoms of GLUT1 deficiency syndrome include epilepsy, abnormal movements, and cognitive delay. The gold standard treatment is the 4:1 ratio (high fat: low carbohydrate and adequate protein) classic ketogenic diet used in refractory epilepsy since 1921. 

In an effort to increase tolerability of the ketogenic diet, the modified Atkins diet (which limits carbohydrates to 10-20 g per day) was introduced in 2003. Both diets improve symptoms, but they can cause long-term problems like high cholesterol, growth problems, acidosis, and kidney stones.

In the study, researchers distributed a 21-question anonymous survey about dietary therapies for epilepsy to attendees at a GLUT1 Deficiency Foundation parent conference in July 2015. Researchers also emailed surveys to families who had registered for the conference but could not attend. 

Ninety-two parents completed the surveys, of which 98% (n=90) used dietary therapies.

Survey responses showed a mean diet duration of 5.5 years, much longer than the recommended two years. Patients also followed a wide variety of diets: the classic ketogenic diet (n=59), the Modified Atkins Diet (n=29), the Medium-chain Triglyceride Diet (n=4), and low glycemic index treatment (n=2). 

Patients started the diet at a mean age of 4.8 years, and most started within months of receiving a GLUT1 deficiency diagnosis. Patients started the ketogenic diet at a younger age than those on modified Atkins or low glycemic index diets (4.1 years vs. 5.9 years, respectively), though 27% of patients switched between diets. 

Key results for patients with epilepsy treated with dietary therapy (n=82):

• >50% seizure reduction in 95% of patients

• >90% seizure reduction in 80% of patients

• Majority (64%) did not need antiepileptics in combination with dietary therapy

• Seizure-free children were

♦ Currently younger (8.2 vs. 11.6 years, P=0.01)

♦ Younger at diagnosis (3.8 vs. 5.3 years, P=0.05)

♦ Less like to be using anticonvulsants (13% vs. 57%, P<0.001)

• All four diets worked about the same for seizure control (P=0.30)

• There was no difference in seizure control for the strictest 4:1 ratio ketogenic diet compared to lower ratio diets (P=0.11)

• Most adverse effects were gastrointestinal

The findings are similar to the largest past study conducted at Columbia University, the authors noted. That study included 64 patients and found that the majority on dietary therapy had seizure reduction of over 90%.3

These results also highlight the importance of early diagnosis of GLUT1 deficiency and early implementation of dietary therapy, they added.

“While alternative treatments, such as the use of triheptanoin, are under clinical investigation, we feel strongly that implementation of dietary therapy should not be delayed after a diagnosis has been made,” they wrote.

“Our survey results, although parent-reported and retrospective in nature, confirm previous reports that consideration could be made for using alternative diets in the GLUT1DS population, especially in the long-term, to improve side effects and tolerability when deemed medically appropriate,” the authors concluded, “In our clinical experience at our institutions, we have both started and transitioned GLUT1DS patients to these alternative diets during adolescence with preliminarily good results. In a few patients who have had worsening of seizures, restarting a high ratio KD [ketogenic diet] has led to rapid resumption of prior seizure control.”

Take-home Points

• Dietary therapy works overwhelmingly well for controlling seizures and abnormal movements in the rare genetic condition GLUT1 deficiency syndrome.

• The classic ketogenic diet, the Modified Atkins Diet, the Medium-chain Triglyceride Diet, and the low glycemic index treatment appear to work equally well for controlling seizures in GLUT1 deficiency syndrome.

• Experts stress the importance of early diagnosis of GLUT1 deficiency syndrome and starting dietary therapy soon after diagnosis.

Dr. Kossoff reports being on the Scientific Advisory Board for Atkins Nutritionals, Inc. Ms. Turner and Ms. Bessone report being Consultants for Nutricia, Inc. The other authors report no conflicts of interest.

 

References:

1. Kass HR, et al. Use of dietary therapies amongst patients with GLUT1 deficiency syndrome. Seizure. 2016 Jan 14;35:83-87.

2. GLUT1 Deficiency Syndrome. Genetics Home Reference. National Institutes of Health. Accessed Feb 4, 2016 at http://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome

3. Pong AW, et al. Glucose transporter type 1 deficiency syndrome: epilepsy phenotypes and outcomes. Epilepsia. 2012;53(1503–1510).