Glucose Transporter-1 (GLUT1) Deficiency Syndrome in Children

Abstract

Summary O ur aim in this study was to try to find the prevalence of glucose transporter type 1 deficiency syndrome in children with intractable epilepsy. So we included 18 patients (9 males and 9 females with an age range of 26-126 months ''mean 59.6± 23.4") with intractable epilepsy who were admitted at the Pediatric Neurology department or followed up at Outpatient Pediatric Neurology clinic, Ain Shams University. All patients had irrelevant perinatal history. None of our patients had documented microcephaly at birth. Concerning family history in included patients: It was positive for seizures in 4 patients (22%), positive for MR in 2 patients (11%) and for microcephaly in 3 (16%) and negative in 14 patients (78%). Nine patients had 1st cousin related parents (50%) and the rest (9 patients "50%") had non related parents. Concerning developmental delay: One patient only had an accepted milestones of development, while 16 patients had developmental delay (89%) and One patient with mental delay only. All patients were exhibiting early onset epilepsy (age of onset ranged from 2-24 months with a mean 5.6 ±5.67) with various forms of seizures (13 patients had generalized form "72%", 5 patients had focal form) which were precipitated by fever in 17 patients (94%), fasting in 3 (17%) and exertion in 14 patients (78%) and with no precipitation in one patient (5.5%). The seizures were occurring at a frequency of 1-140 times/week as a range (mean 28.2 ±32) for a period of time ranged from 24-114 months (mean 51 ±22.15). About AED,there were 13 patients (72%) on 2 drugs and 4 (22%) on 3 drugs and one patient(5.5%) on 5 drugs for a duration ranged from 12-84 months (mean 41.0 ±18.36). All cases were subjected to detailed neurological examination during the study, there were 9 patients (50%) found to have microcephaly,one patient (5.5%)with macrocephaly (head circumference diameter below 5th percentile in correlation to age and sex). Also we found that, five patients (28%) had hypotonia, 5 had hypertonia (28%) and 8 patients had normal tone (44%). And 4 patients with hypo-reflexia (22.5%),6 with hyper-reflexia (33.5%) and 8 patients with normal reflexes (44%). All patients had normal blood glucose level after 4-6 hours of fasting in samples obtained just before lumbar puncture and normal serum lactate. CSF samples from all patients were examined for: 1- Glucose level (>60 mg/dl in 7 patients "39%", =<60 mg/dl in 11 patients "61%" two of them with CSF glucose <40 mg/dl "). 2- Lactate level (NormaL <16.2 mg/dl in all patients). 3- Cytology and proteins (normal findings in all patients). MRI reports showed normal findings in 12 patients (67%), brain atrophy in 4 patients (22%), subvolemic changes in one patient (5.5%) and minimal ventricular dilatation in one patient (5.5%). EEG reports had no epileptogenic activity in 9 patients (50%), and generalized activity in 5(27.5%) and focal activity in 4 patients (22%). In our study we considered patients to be having GLUT-DS (11 patients 61%) if they had low CSF glucose level <60 mg/dl, following four to six hours of fasting with normal blood glucose level (60-180 mg/dl). We found that CSF glucose is <40 mg/dl in two patients out of 11 (18%) and one patient with CSF /blood glucose ratio <0.45%. The suspected 11 patients were 7 males and 4 females with an age ranged from 29-126 months (mean 62.3 ±27.6) with 2 patients (18%) of them were having positive family history of similar condition and 5 patients had first cousin related parents(45%), Age of first seizure experience ranged from 2-24 months of age (mean 6.8 ±6.77) with a range of 27-114 months as duration of the disease (mean 53.5 ±26.4) so there were 4 patients (36%) on 2 drugs, 4 patients on 3 drugs(36%) and one patient on 5 drugs(9%) for a duration ranged from 24-84 months (mean 41.5 ±19.1). Seizures were generalized in 7 patients (54%), focal in 4 (36%) with a frequency ranged from 2 -140 times per week (mean 30.1±38.5). Seizures and movement disorders (2 with chorea,4 with dystonia, one patient with choreoathetosis) were precipitated by fever in 9 patients (82%), fasting in 2 (18%), and by exertion in 8 patients (73%). On Examination, there were five patients (45%) found to have microcephaly. Also we found that, three patients had hypotonia (27%), 2 patients had hypertonia (18%) and 6 patients had normal tone (55%), and 3 patients with hypo-reflexia (27%), 2 with hyper-reflexia (18%) and 6 patients with normal reflexes (55%).