T.P.34

We report a 44-years-old man, who presented, since the age of 20, recurrent episodes of rhabdomyolysis after exercise or prolonged fasting; he also showed a mild mental retardation and sporadic choreo-athetoid movements. His 14-years-old son had a psychomotor developmental delay with episodes of drowsiness and head drops, occurring mainly at fasting, and exercise-induced choreo-athetoid movements but no history of pigmenturia. Neurological examination revealed microcephaly, mild spastic ataxia and mental retardation. EEG was normal in the proband but in the son showed, during fasting, diffuse spike-wave discharges disappearing after food intake. Brain MRI was normal in both. CSF analysis in the son revealed hypoglycorrhachia (40 mg/dl). Clinical and laboratory findings suggested a search for mutations in SCL2A1 (GLUT-1) gene that revealed in both subjects, an already reported pathogenic heterozygous mutation (R333W). GLUT-1 Deficiency Syndrome (DS) is a rare encephalopathy, caused by impaired glucose transport into the brain, presenting with early-onset epilepsy, movement disorders, developmental delay and microcephaly but rhabdomyolysis has never been reported in similar cases. To better define the origin of recurrent exercise-induced rhabdomyolysis in the father, he underwent forearm ischemic test (normal), EMG (myopathic pattern) and muscle biopsy that evidenced unspecific changes. Muscle biochemical studies excluded the most common metabolic causes of recurrent rhabdomyolysis, but VLCAD gene analysis in the father showed two known heterozygous mutations (p.G185S and p.R385W) whereas his son carried only the p.G185S. Nowadays, it is evident that cases of “double trouble” are increasing and, when a known phenotype is accompanied by some atypical features, we should think of an alternative explanation of unusual presentations.