3.1.2 Disorders of brain metabolism in children

Since ketogenic diets induce a shift away from glycolytic energy production towards mitochondrial oxidative phosphorylation, they are the treatment of choice in two childhood disorders of impaired brain glucose metabolism: glucose transporter type 1 deficiency syndrome (GLUT1 DS) and pyruvate dehydrogenase complex deficiency (PDHD) [2]. In both cases, the ketones produced by the diet bypass the metabolic defects, serving as an alternative energy source for the brain.

GLUT1 DS results from impaired glucose transport across the blood-brain barrier due to mutations in the SLC2A1 gene, which encodes the glucose transporter, GLUT1 [36]. Clinically, GLUT1 DS is characterized by cognitive impairment, mixed seizure types, and a complex movement disorder. The vast majority of children with GLUT1 DS achieve seizure freedom with a CKD, which should be introduced as early as possible and continued through to adulthood [36]. The CKD may be difficult to tolerate in older children and adolescents, in which case the MAD is also effective [2]. In GLUT1 DS, ketogenic diets may also enhance the child's alertness, and they frequently improve the movement disorder [36].

In PDHD, pyruvate is unable to be metabolized into acetyl-CoA, resulting in abnormal mitochondrial metabolism and lactic acidosis [37]. Clinically, PDHD is characterized by seizures, severe encephalopathy, and—usually—death during childhood. The CKD is effective and safe in PDHD, and appears to increase longevity and improve mental development [37]. However, severe forms of PDHD may not be appropriate for the diet if quality of life is not improved [2].
