GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder.
Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities.
Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Drive, Los Angeles, CA 90048, USA. john.graham@cshs.org
John M
JM
Graham
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D011596:Psychomotor Disorders / Q000175:diagnosis* / Q000235:genetics; D013577:Syndrome; D055815:Young Adult
D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human