Childhood chorea with cerebral hypotrophy: a treatable GLUT1 energy failure syndrome

Arch Neurol. 2009 Nov;66(11):1410-4. doi: 10.1001/archneurol.2009.236.

Abstract

Objective: To expand the spectrum of glucose transporter type 1 deficiency syndromes with a novel clinical and radiological phenotype not associated with microcephaly.

Design: Case report.

Setting: Two academic medical centers. Patient A 7-year-old patient followed up for 4 years.

Results: The patient exhibited a predominant syndrome of chorea and mental retardation associated with a combination of paroxysmal ataxia, dysarthria, dystonia and aggravated intellectual disability induced by fasting or exertion. She harbored a sporadic, heterozygous amino acid insertion in the GLUT1 transporter (insY292) that, in all likelihood, impaired blood-brain glucose flux. Her brain configuration appeared hypotrophic via magnetic resonance imaging, particularly over the occipital lobes. A ketogenic diet resulted in brain growth that accompanied a favorable symptomatic outcome.

Conclusions: To date, glucose transporter type 1 deficiency syndrome includes several epileptic and movement disorder phenotypes caused by the clinical expressivity of the prominent cortical, basal ganglia, and cerebellar abnormalities found in the disease, but hypomorphic or novel variants are probably yet to be discovered.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Brain / pathology*
  • Brain Diseases, Metabolic, Inborn / diet therapy*
  • Brain Diseases, Metabolic, Inborn / genetics
  • Brain Diseases, Metabolic, Inborn / pathology
  • Carbohydrate Metabolism, Inborn Errors / diet therapy
  • Carbohydrate Metabolism, Inborn Errors / genetics
  • Carbohydrate Metabolism, Inborn Errors / pathology
  • Child
  • Child, Preschool
  • Chorea / diet therapy
  • Chorea / genetics*
  • Chorea / pathology
  • Developmental Disabilities / genetics
  • Diet, Ketogenic*
  • Excitatory Amino Acid Transporter 2 / genetics*
  • Female
  • Glucose / metabolism
  • Humans
  • Intellectual Disability / genetics
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Syndrome

Substances

  • Excitatory Amino Acid Transporter 2
  • Glucose