ABSTRACT
AIM: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). METHODS: This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. RESULTS: The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. CONCLUSION: Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort.
Subject(s)
Ataxia/etiology , Brain Diseases, Metabolic, Inborn/diet therapy , Brain Diseases, Metabolic, Inborn/etiology , Developmental Disabilities/etiology , Glucose Transporter Type 1/deficiency , Seizures/etiology , 3-O-Methylglucose/pharmacokinetics , Anticonvulsants/therapeutic use , Brain Diseases, Metabolic, Inborn/diagnosis , Carbohydrate Metabolism, Inborn Errors/diet therapy , Carbohydrate Metabolism, Inborn Errors/etiology , Child , Diet Therapy , Female , Glucose Transporter Type 1/genetics , Humans , Infant , Lumbar Vertebrae , Male , Seizures/drug therapy , Spinal Puncture , Syndrome , Treatment OutcomeABSTRACT
Generalized epilepsy with febrile seizures plus (GEFS(+)) is an important childhood genetic epilepsy syndrome with heterogeneous phenotypes, including febrile seizures (FS) and generalized epilepsies of variable severity. Forty unrelated GEFS(+) and FS patients were screened for mutations in the sodium channel beta-subunits SCN1B and SCN2B, and the second GEFS(+) family with an SCN1B mutation is described here. The family had 19 affected individuals: 16 with typical GEFS(+) phenotypes and three with other epilepsy phenotypes. Site-specific mutation within SCN1B remains a rare cause of GEFS(+), and the authors found no evidence to implicate SCN2B in this syndrome.
Subject(s)
Epilepsy, Generalized/genetics , Protein Subunits , Seizures, Febrile/genetics , Sodium Channels/genetics , Amino Acid Substitution , Child , Child, Preschool , Comorbidity , Epilepsy, Generalized/epidemiology , Female , Genetic Linkage , Genetic Markers , Genetic Testing , Haplotypes/genetics , Humans , Infant , Infant, Newborn , Male , Mutation , Nerve Tissue Proteins/genetics , Pedigree , Phenotype , Queensland/epidemiology , Seizures, Febrile/epidemiology , Voltage-Gated Sodium Channel beta-2 SubunitABSTRACT
We studied the patterns of standing in children with neuromuscular disorders and central hypotonia for Gowers' sign, and compared these two groups with healthy controls. More children with central hypotonia than controls rolled prone before standing at 36 months; at this age all children with neuromuscular disorders rolled prone. Neurological assessment is indicated in children continuing to roll prone before standing at 3 years.
