Novel insight into GLUT1 Deficiency Syndrome: screening for emotional and behavioral problems in youths following ketogenic diet

BACKGROUND: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1DS) is a rare disorder with a broad spectrum of neurological manifestations. The ketogenic diet (KD) is, to date, the gold standard treatment. Behavioral problems, well recognized in patients with chronic conditions, have not been, so far, deeply investigated in GLUT1DS patients. We performed an exploratory study to assess the risk of emotional and behavioral problems and investigated the potential role of influencing factors related to the pathology itself or KD treatment.METHODS: This was a mono-center retrospective study involving youths patients with GLUT1Ds treated with KD and a group of migraine patients age- and gender-matched. Patients were included if the main caregiver completed the Child Behavior Check List 6-18 (CBCL). Descriptive statistics for demographic and clinical data and questionnaire scores were computed. Correlational analyses were used to assess the potential associations of clinical variables and age and time from KD introduction with CBCL scores in GLUT1DS patients.RESULTS: We enrolled nine youths with GLUT1DS and 9 with migraine. In the GLUT1DS group, none of the mean scores of the CBCL items fell within the borderline/clinical range, except for social problems located in the borderline range. Investigation for influencing factors revealed the patient's age related to withdrawn/depressive (r=.709, p=.032) and social problems (r=.684, p=.042). Time from the introduction of KD was related to social problems (r=.827, p=.006). From the comparison with the scores obtained from migraine patients, significantly higher scores emerged in the latter group in internalizing problems (Z= -2.48, p = .01), externalizing problems (Z= -3.49, p < .001), anxious/depressed subscale (Z= -2.37, p=.014), somatic complaints subscale (Z= -2.624, p=.008), aggressive behavior subscale (Z= -2.539, p=.011).CONCLUSIONS: Although highly exploratory in its nature, this study provides a novel insight into GLUT1DS. Our data suggested that the risk for internalizing problems in GLUT1DS youths was related to higher age and higher time elapsed from KD introduction. They occurred at a sub-clinical level, making them difficult to detect, if not expressly and systematically investigated.