A multicenter international genetic and clinical study of GLUT1 deficiency received 132 requests for mutational analysis of SLC2A1 gene from 2004-8. Mutations identified in 57 patients (43%) were novel in 37, known in 6, and multiple exon deletions in 6. Clinical data retrospectively collected by questionnaire revealed three different phenotypes: 1) classical (84%), early onset (<2 years) (65%) and late-onset (18%); 2) non-classical with mental retardation and movement disorder, without epilepsy (15%); and 3) one adult case with minimal symptoms. The ketogenic diet controlled epilepsy in 86% and reduced movement disorders in 48% patients with classical phenotype and in 71% of non-classical. Delay in diagnosis of classical cases was 6.6 years (range, 1 month-16 years). CSF glucose was <2.5 mmol/1 (range 0.9-2.4 mmol/1), and CSF:blood glucose ratio was <0.5 in all but one (range 0.19-0.52). CSF lactate was low to normal. Type of mutation was related to severity of phenotype. CSF:blood glucose ratio was related to type of mutation and phenotype. [1]

COMMENT. Lumbar puncture with CSF glucose determination was the key to diagnosis of GLUT1 deficiency and prompt treatment with the ketogenic diet. Seizures were not a symptom in 15% of patients.