Abstracts

Rationale: GLUT-1 Deficiency Syndrome (DS) is a rare condition caused by impaired glucose transport into the brain. GLUT1 DS was first reported in children with intractable epilepsy, ataxia, acquired microcephaly, spasticity and mental retardation. Thereafter phenotypic spectrum greatly widened including paroxysmal movement disorders and more or less severe seizure disorders, alone or in combination. Cognitive impairment, if present, may vary from mild to severe. We herein report a family with GLUT1 DS in which the proband presents an unusual phenotype, with exercise-induced rhabdomyolysis (EIR) as the main clinical manifestation. Methods: - Results: A 44-year-old man presents, since the age of 20, recurrent episodes of rhabdomyolysis after intense physical exercise and prolonged fasting. At times, choreoathetotic movements involving upper limbs appeared after effort. He never had epileptic seizures. Neurological examination was unremarkable. Neuropsychological evaluation revealed moderate cognitive impairment. Lactacidemia after forearm ischemic or aerobic exercise tests was normal. EMG was myopathic but muscle biopsy showed only unspecific changes. Biochemical studies ruled out the most common causes of recurrent rhabdomyolysis. His 14-year-old son had a typical GLUT1 deficiency encephalopathy with severe mental retardation, ataxia, spastic tetraparesis, microcephaly, paroxysmal exercise-induced dyskinesia and drug-resistant seizures mainly appearing before meal and disappearing after food intake. EMG was normal. CSF analysis revealed low glucose level (CSF/serum glucose ratio 0,44; normal value > 0,55). Molecular analysis for SCL2A1 (GLUT-1) gene showed a pathogenic heterozygous mutation (R333W) in both the patients. Conclusions: To our knowledge, this is the first report of EIR associated to GLUT1-DS. The low prevalence of both conditions, the exclusion of the most common causes of EIR, the facilitating effect of fasting on EIR occurrence, strongly support the hypothesis that these two conditions are causally related.