Sodium Lactate Infusion in GLUT1DS Patients

In glucose transporter 1 deficiency syndrome (GLUT1DS) cerebral glucose uptake from the systemic blood circulation is limited, because of deficient transport of glucose across the blood-brain barrier by the transporter protein (GLUT1). Classically patients present with developmental problems, movement disorders and severe epilepsy. There is no curative treatment for GLUT1DS, and anti-epileptic drugs usually have little to no effect. The ketogenic diet, providing ketones as an alternative energy substrate for the brain is an effective treatment option for the epilepsy and movement disorders in many GLUT1DS patients. Unfortunately, not in all GLUT1DS patients the ketogenic diet has a positive effect and other treatment options for these patients are very limited.

Traditionally, lactate is seen as a waste product of glycolysis during anaerobic conditions and a marker of ischemia. Interestingly, research has shown the beneficial side of lactate as an energy source for different organs. It seems that the brain can indeed use lactate as an alternative energy metabolite, besides glucose and ketones. The aim of this study is to investigate whether lactate can be an alternative energy metabolite in the GLUT1DS brain, and reduce epileptic discharges on EEG when intravenously administered in patients with GLUT1DS.

Inclusion criteria

• Diagnosed with GLUT1DS and known in our center.
• Baseline characteristics include a high frequency of clinical seizures and epileptic discharges on EEG.
• History of trying ketogenic diet with good compliance without beneficial effects.
• Age > 6 years.
• Informed consent.

Exclusion criteria

• Additional medical condition or illness that impairs the patient's ability to participate in the study (for example actual treatment of a malignancy, active infection, poorly controlled diabetes mellitus, hypertension, organ failure, clinically significant haematological or biochemical abnormalities).
• Elevated serum sodium (> 145 mmol/L).
• Participation in another interventional study at start of the study or during the study.
• Presence of known panic disorders or a history of panic attacks.