Diagnostic Challenges Associated with GLUT1 Deficiency: Phenotypic Variabilities and Evolving Clinical Features
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GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnoseddue to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical courseof nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developedseizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showedmovement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was notuniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures andmovement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency canbe challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patientswith epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient’s quality of life.
Abstract
GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnoseddue to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical courseof nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developedseizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showedmovement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was notuniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures andmovement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency canbe challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patientswith epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient’s quality of life.
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