glucose transport protein type 1 ( glut1 ) delivers glucose to the brain from bloodstream and is therefore crucial for an adequate energy provision .
glut1 deficiency syndrome , inducing a chronic brain energy failure , is caused by mutations of the solute carrier family 2 ( facilitated glucose transporter ) member 1 ( slc2a1 ) gene , located on the chromosome 1p34.2 .
the classic phenotype of glut1 deficiency syndrome is characterized by : mild to severe motor delay and mental retardation ; infantile - onset epilepsy ; head growth deceleration , possibly resulting in acquired microcephaly ; movement disorders ( ataxia , dystonia , spasticity ) ; and non - epileptic paroxysmal events ( intermittent ataxia , periodic confusion , recurrent headaches ) .
reported features of epilepsy in this condition are heterogeneous ; generalized tonic - clonic and absence seizures prevail .
lumbar puncture shows hypoglycorrhachia , with a reduced cerebrospinal fluid / blood glucose ratio in most patients .
the ketogenic diet has proved to markedly improve epilepsy , movement disorders and head growth , while the cognitive effects are less pronounced .
the patient 's family history was positive for : a not better specified psychiatric disorder and somnambulism in the mother ; epilepsy and mental retardation , in a paternal uncle and a paternal cousin , respectively .
he was an only child , born at the 36 week of gestation by caesarean section due to hypertensive gestosis , after a two - placenta twin pregnancy , with the intrauterine death of the other fetus .
apgar index was 7 ( 1 ) and 8 ( 5 ) ; birth weight was 3040 grams .
cyanosis and jaundice at the birth were reported ; jaundice was treated by phototherapy and exsanguinotransfusion .
at the age of 4 years 1 month , eeg tracing during wakefulness , performed due to the psychomotor retardation , was normal . from the age of about 4 years
he has suffered from headache several times monthly , sometimes associated with nausea and vomiting , treated with paracetamol . at the age of about 6 years
, he started to present , especially in the morning , short but frequent ( even several times a day ) episodes of loss of consciousness , eye closure , inconstant eyelid myoclonia .
the events could occur isolated or close together resulting in falling asleep but showing amelioration on awakening .
the drowsiness associated with the long clusters of these events was a major problem in his everyday life , especially at school .
neurological examination showed only a mild , aspecific incoordination ; head circumference corresponded to the fiftieth percentile .
neuropsychological evaluation showed a mild mental retardation ( wechsler scale ) , stable during the follow - up , with a significant prevalence of verbal intelligence quotient ( iq ) versus performance iq ; an aspecific learning disorder was evident .
eeg revealed diffuse paroxysmal abnormalities and several brief absence seizures have been recorded [ figures 1 and 2 ] .
high - resolution kariotype and search for fragile x syndrome were normal , as well as a metabolic screening including creatine kinase , lactic acid at baseline and after exercise , thyroid hormones , tests for celiac disease , ammonia , serum and urinary aminoacids , and urinary oligosaccharides .
absence seizures were drug resistant to ethosuximide , levetiracetam , lamotrigine , and valproate , with only transient improvements after beginning a drug .
after antiepileptic therapy start , we found episodic , mild postural and tremor - like action dyskinesias in the arms . at the age of 15 years
, mainly due to the drug - resistant absence seizures , we performed the molecular analysis of the slc2a1 gene .
the polymerase chain reaction sequencing of all exons revealed a nucleotide deletion in heterozygosity , 
c.1336_1338del  , causing the loss of one amino acid ( isoleucine : p.ile446del ) .
we chose not to give the lumbar puncture to avoid causing the patient excessive discomfort .
a ketogenic diet was started and we noted a fast , marked clinical improvement . the boy became more responsive and active , while absence seizures and headache frequency decreased . however , patient 's compliance with the prescribed dietary regimen was so poor that after 1 year we decided to stop the diet .
only a few days after the discontinuation , the boy showed clinical worsening , which made him willing to resume the diet .
eeg recording , at the age of 14 years , showing diffuse bilateral and frontal dominant spike and wave discharges during wakefulness : open eyes on the left , closed eyes on the right eeg recording , at the age of 14 years , showing diffuse bilateral spikes and waves during hyperpnea , once associated ( see arrows ) with a brief absence seizure
a constant supply of glucose is the most important source of energy for the brain .
therefore , glut1 deficiency syndrome could be considered as a brain energy failure prototype . during last years
also the three following clinical pictures have been described : ( a ) carbohydrate - responsive phenotype , characterized by clinical worsening ( motor and mental performance , seizures ) with fasting and improvement with carbohydrate intake ; ( b ) movement disorder without epilepsy , characterized by ataxia , dystonia , spasticity , mild delay of motor and mental development , normal or decelerated head growth ; ( c ) paroxysmal exertion - induced dyskinesias ( dystonia , choreoathetosis , ballism ) and epilepsy . the case we have described shows an atypical phenotype of glut1 deficiency syndrome .
no movement disorders were present ( except for slight tremor after antiepileptic therapy start , probably a side effect of antiepileptic drugs ) , nor decrease of head circumference has been detected .
the phenotype of our patient does not fully fit in any of the clinical pictures described so far in association with glut1 deficiency . in 2010 , leen et al .
reported 10 cases with the so - called late - onset classical phenotype , but only in one of them movement disorders were absent and the reported features of seizures were different compared to those of our patient .
it is true that epilepsy with the absence seizures is among those most frequently described in glut1 deficiency syndrome , but more often it has an early onset ( before the age of 4 ) , while in the forms with later onset , as in our patient , the combination of drug - resistant absence seizures ( without other types of seizures ) and mental retardation , present in the case we have reported , has not been described .
considering the findings of our patient 's eeg ( initially normal , then clearly pathological ) , our data confirm what pong et al
. stated , namely that in the same individual , affected by this disorder , eeg picture could change over time .
our case report suggests that , in the lack of a better definition of the possible phenotypes associated with glut1 deficiency , there is a risk of underestimating the actual occurrence of the disease . especially because of the atypical phenotypes ,
this fact has important implications also for the treatment , because a ketogenic diet , that should begin as soon as possible , could significantly improve the quality of life of these patients , while classic antiepileptic drugs usually fail .
in fact , a high - fat diet leads to the production of ketone bodies bypassing the glut1 deficiency and providing an alternative source of energy to the brain .
incidentally , we emphasize that the exact pathogenetic mechanism of the formation of cataracts , also present in our patient , is currently unknown . in conclusion ,
it is recommended to consider this diagnostic hypothesis in any case with an unexplained neurological disorder , also when , as in our case , a main clinical feature consists of drug - resistant seizures associated with a global developmental delay , even in the lack of a movement disorder , according to klepper suggestions .
 the glucose transport protein type 1 ( glut1 ) deficit causes a chronic brain energy failure . 
 the classic phenotype of glut1 deficiency syndrome is characterized by : mild to severe motor delay and mental retardation ; infantile - onset epilepsy ; head growth deceleration ; movement disorders ( ataxia , dystonia , spasticity ) ; and non - epileptic paroxysmal events ( intermittent ataxia , periodic confusion , recurrent headaches ) . during last years 
 the classic phenotype of this syndrome , as originally reported , has expanded . 
 we report the atypical phenotype of a boy with glut1 deficiency syndrome , characterized by mild mental retardation and drug - resistant absence seizures with onset at the age of 6 years , without movement disorders nor decrease of head circumference . 
 a prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment . 
Introduction
Case Report
Discussion