GLUT1 deficiency syndrome-1 is a neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype is characterized by an encephalopathy marked by infantile seizures that is refractory to treatment (anticonvulsants), deceleration of cranial growth leading to microcephaly, psychomotor retardation, spasticity, ataxia, dysarthria, dystonia, opsoclonus and other paroxysmal neurological phenomena (confusion, lethargy, sleep disturbance, and headache), often worse prior to meals. Affected infants appear normal at birth following an uneventful pregnancy and delivery. Birth weight and Apgar scores are normal. Seizures begin between age one and four months in 90% of cases. Apneic episodes and abnormal episodic eye movements simulating opsoclonus may precede the onset of seizures by several months. Five seizure types occur: generalized tonic or clonic, myoclonic, atypical absence, atonic, and unclassified. The frequency and severity of seizures varies among affected individuals. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe mental retardation.
The diagnosis of GLUT1 deficiency is based on the clinical picture and biochemical analysis of the cerebrospinal fluid (CSF). It is established in neurologically impaired individuals with hypoglycorrhachia (reduced CSF glucose concentration, less than 40 mg/dl) and low CSF lactate. The ketogenic diet is highly effective in controlling the seizures and is generally well tolerated because ketone bodies are easily transported across tissue membranes, and they are readily available for uptake and metabolism by brain cells. However, neurobehavioral and motor deficits persist in most cases. Despite that, correct diagnosis of GLUT1 deficiency is still important because early initiation of the ketogenic diet may result in better seizure control and improved neurobehavioral development.