Glucose transporter type 1 deficiency syndrome and the ketogenic diet

Schwantje, Marit; Verhagen, Lilly M.; Hasselt, Peter M. van; Fuchs, Sabine A.

doi:10.1002/jimd.12175

Cited by 35 publications

(42 citation statements)

References 12 publications

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“…The age at the onset of symptoms was lower in our patients with epilepsy and in the SLC2A1 (+)-group, and the time from debut to the onset of treatment was significantly higher. Most studies describe a delay of at least 4 years from debut to the onset of the diet [ 13 , 17 , 19 ]. Therefore, KDT should be onset when a GLUT1DS is suspected, although the definitive diagnosis is not made.…”

Section: Discussionmentioning

confidence: 99%

“…The current standard treatment for GLUT1DS are the KDT, especially the CKD [ 4 , 6 , 12 , 19 , 20 ]. Recent reviews have reported that 60% of the patients were seizure-free after the implementation of the diet, and 80% of patients with movement disorders improved [ 3 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…When a GLUT1DS is confirmed, KDT should be used life-long. However, CKD is a very restricted diet, and non-compliance is a frequent reason for withdrawal, as reported a while ago [ 13 ] and recent [ 19 ] referring figures of 18%. Considering that MAD may be as effective as CKD, and that MAD is less restrictive, the type of KDT chosen should be individualized [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

et al. 2021

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Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. Methods: An observational descriptive study was conducted to describe 18 children (January 2009–August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. Results: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. Conclusions: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

et al. 2021

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“…Patients with GLUT1-DS have historically been treated with the KD since it provides an alternate source of energy (ie, ketone bodies) that circumvents the brain's glucose deficiency ( Figure 1) and alleviates most of GLUT1 deficiency symptoms. 70,71 KD metabolites, principally circulating ketone bodies such as acetoacetate and beta-hydroxybutyrate, act as substitutes for glucose by subsequent conversion into acetyl-CoA, which then enters the citric acid cycle and is terminally oxidized in mitochondria to produce ATP. Ketone bodies are mostly generated by the liver, enter the peripheral circulation, and are then transported into the brain through (MCTs); they do not require a functional glucose transporter to be utilized.…”

Section: Kd Contraindicationsmentioning

confidence: 99%

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms

Gavrilovici

Rho

2020

J of Inher Metab Disea

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Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates—such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti‐inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism‐based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long‐term outcomes for patients.

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“…Available efficacy data confirm that KDTs can be maintained with good compliance in pediatric and adolescent patients [ 1 , 8 ]. In particular, in a recent review by Schwantje and colleagues [ 9 ], it has been demonstrated that compliance with a ketogenic diet (KD) is higher than 80% in the GLUT1DS population. The conditions turn out to be more complicated for DRE patients.…”

Section: Introductionmentioning

confidence: 99%

Families’ Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey

Pasca

Varesio²,

Ferraris

et al. 2020

Nutrients

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Objective: To describe families’ experiences in managing epileptic patients undergoing ketogenic dietary therapies (KDTs) in acute medical settings. Methods: We conducted a short online survey addressed to the families of patients undergoing a classic ketogenic diet (cKD) for at least three months. The survey was composed of 18 questions exploring the following issues: demographic characteristics, epilepsy diagnosis, ketogenic-diet treatment history, the reason for emergency-ward admission and patient management, surgery-procedure management, and outcomes. Results: A sample of 50 families agreed to participate. Out of 50 patients, 33 (66%) had been undergoing a cKD for more than two years. Fifteen (30%) patients had been admitted at least once to the Emergency Room (ER), and 8.2% had undergone surgical procedures during cKD treatment. The causes of ER admission were the following: seizures, infection, trauma, and gastrointestinal or respiratory problems. In 75% of cases, blood ketonemia was not monitored during ER admission, and according to 46% of responders, the medical staff intervening did not have a basic knowledge of KDTs. Conclusions: According to both our experience and caregivers’ reports, it might be useful to search for standardized specific approaches to patients undergoing KDTs in the emergency setting.

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Glucose transporter type 1 deficiency syndrome and the ketogenic diet

Cited by 35 publications

References 12 publications

Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms

Families’ Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey

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