The case described illustrates several principles: first, unsuspected GD phenotypes are likely to remain unidentified until genotyping replaces the ascertainment bias introduced by diagnostic criteria currently in use. Second, genotype-phenotype correlations in GD seem implausible from the analysis of the approximately 125 patients that have been described in the literature.9,15- 20 While it is not feasible to predict the structural disruption induced by the insertion mutant described in this report, neighboring mutations alter the cellular expression, targeting, and function of GLUT1 in unpredictable ways when considered against the transporter primary and proposed tertiary structures.9 Third, the clinical semiology of GD states includes static neurological impairments (often manifested as mental retardation, spasticity, dysarthria, ataxia, and dystonia, either together or in various syndromic combinations18,21) in conjunction with paroxysmal events such as epilepsy, flaccidity, dyskinesia, or opsoclonus. Often, but not invariably, these states manifest in the context of small fluctuations in blood glucose concentration, such as those achieved by fasting or nourishing individuals with otherwise unimpaired carbohydrate metabolism.4 Except for rare exceptions such as the case presented here and another case that involved delayed cerebral myelination,22 the neurological substrate has appeared uninformative from a structural point of view (to our knowledge, no pathological analysis of GD has yet been undertaken), while cerebral glucose uptake has proven remarkably and uniformly altered over select brain regions.14 In fact, even transient hypoglycemia during infancy has been associated with a clinical-metabolic imaging phenotype similar to GD.8 Therefore, the phenotype is not accounted for by brain structure or brain glucose uptake, although, to our knowledge, quantification of glycolysis has not yet been attempted in GD. Of the 4 fundamental derivatives of brain fuels (brain matter, adenosine triphosphate, and the neurotransmitters glutamate and γ-aminobutyric acid), only the first has been investigated (and proven abnormal) in mice23,24 and human patients,8 both of which can have microcephaly. Therefore, fluctuations in adenosine triphosphate levels or neurotransmitter action across different cerebral networks may account for the pleomorphic phenotypes of GD syndromes. The results invite further considerations: only select features of neuroglycopenia (including that caused by GD) may be treatable. In other words, all the paroxysmal manifestations of the disease, and perhaps brain growth, can be significantly ameliorated, whereas the impairment of intelligence and thalamocortical metabolism persists,8 which underscores the developmental role of glucose on cerebral maturation and serves as the defining feature of GD.