The
ketogenic diet (KD), established to treat intractable childhood
epilepsy, has emerged as the principal treatment of
GLUT1 deficiency syndrome (OMIM 606777). This defect of
glucose transport into the brain results in hypoglycorrhachia causing
epilepsy, developmental delay, and a complex motor disorder in early childhood.
Ketones provided by a high-fat,
low-carbohydrate diet serve as an alternative fuel to the brain.
Glucose,
lactate,
lipids, and
ketones in blood and cerebrospinal fluid were investigated in five GLUT1-deficient patients before and on the KD. Hypoglycorrhachia was detected in the non-ketotic and ketotic state. In
ketosis,
lactate concentrations in the cerebrospinal fluid increased moderately. The CSF/blood ratio for
acetoacetate was higher compared to
beta-hydroxybutyrate.
Free fatty acids did not enter the brain in significant amounts. Blood concentrations of
essential fatty acids determined in 18 GLUT1-deficient patients on the KD were sufficient in all age groups. The effects of the KD in
GLUT1 deficiency syndrome, particularly the course of blood
lipids, are discussed in an illustrative case. In this syndrome, the KD effectively restores brain energy metabolism.
Ketosis does not influence impaired GLUT1-mediated
glucose transport into brain: hypoglycorrhachia, the biochemical hallmark of the disease, can be identified in GLUT1-deficient patients on a KD. The effects of
ketosis on the concentrations of
glucose,
lactate,
ketones, and
fatty acids in blood and cerebrospinal fluid in this entity are discussed in view of previous data on
ketosis in man.