Abstract
IntroductionGlucose Transporter Type I Deficiency Syndrome (GLUT1DS) classical symptoms are seizures, involuntary movements, and cognitive impairment but so far the literature has not devoted much attention to the last.MethodsIn our retrospective study involving 25 patients with established GLUT1DS diagnosis, we describe the cognitive impairment of these patients in detail and their response to the ketogenic diet in terms of cognitive improvement.ResultsWe outlined a specific cognitive profile where performance skills were more affected than verbal ones, with prominent deficiencies in visuospatial and visuomotor abilities. We demonstrated the efficacy of ketogenic diet (KD) on cognitive outcome, with particular improvement tin total and verbal IQ; we found that timing of KD introduction was inversely related to IQ outcome: the later the starting of KD, the lower the IQ, more notable nonverbal scale (verbal IQ correlation coefficient −0.634, p‐value = 0.015). We found a significant direct correlation between cognition and CSF/blood glucose ratio values: the higher the ratio, the better the cognitive improvement in response to diet (from T0–baseline evaluation to T1 on average 18 months after introduction of KD‐: TIQ correlation coefficient 0.592, p‐value = 0.26; VIQ correlation coefficient 0.555, p‐value = 0.039). Finally, we demonstrated that a longer duration of treatment is necessary to find an improvement in patients with “severely low ratio.”ConclusionOur results were consistent with the hypothesis that timing of the diet introduction is a predictive factor of cognitive outcome in these patients, confirming that earlier initiation of the diet may prevent the onset of all GLUT1DS symptoms: epilepsy, movement disorders, and cognitive impairment.
Highlights
Glucose Transporter Type I Deficiency Syndrome (GLUT1DS) classical symptoms are seizures, involuntary movements, and cognitive impairment but so far the literature has not devoted much attention to the last
Since the first description of the disease by De Vivo et al (1991), different studies have led to identification of “common manifesta‐ tions” of this disease and “uncommon manifestations” that suggest a high probability of GLUT1DS as a clinical diagnosis (De Giorgis, Varesio, Baldassari, Olivotto, & Veggiotti, 2016)
Involuntary movements are common symptoms of GLUT1DS (De Giorgis et al, 2016) which demon‐ strated a positive response to ketogenic diet (KD), (Leen et al, 2010; Veggiotti et al, 2010), even if improvement was less evident compared to the effect on seizures
Summary
Glucose Transporter Type I Deficiency Syndrome (GLUT1DS) is a metabolic disorder due to mutations in SLC2A1 gene (1p 31.3→35) (Shows et al, 1987) which encodes for a specific transporter of glu‐ cose in the brain. In Ramm‐Pettersen et al 2014 after 14 months of KD, a patient gained 21 points of TIQ from 42 to 63 on Wechsler Preschool and Primary Scale of Intelligence (WPPSI III) (Wechsler, 2008); a patient in De Giorgis et al 2015, after 2 years of diet, gained 10 points of TIQ from 79 to 89 on WISC III. Besides these rare reports, the cognitive profile in GLUT1DS has not been deeply characterized so far. The aim of our study was to describe the cognitive profile in GLUT1DS patients, before and after the KD introduction, in order to define a specific cognitive profile—in terms of trend of specific indexes of Wechsler Intelligence Scales (total, verbal, and non ver‐ bal) and individual subtests—to correlate it to GLUT1 phenotype and outcome after KD introduction
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