Valentina De Giorgis1, Federica Teutonico2, Cristina Cereda3, Umberto Balottin4, Marika Bianchi3, Lucio Giordano5, Sara Olivotto1, Francesca Ragona6, Anna Tagliabue7, Giovanna Zorzi6, Nardo Nardocci6, Pierangelo Veggiotti8. 1. Brain and Behaviour Department, University of Pavia, Pavia, Italy. 2. Child and Adolescence Neuropsychiatry Unit, "G. Salvini" Hospital, Rho, Italy. 3. "C. Mondino" National Neurological Institute, Pavia, Italy. 4. Brain and Behaviour Department, University of Pavia, Pavia, Italy; Department of Child Neurology and Psychiatry, "C. Mondino" National Neurological Institute, Pavia, Italy. 5. Pediatric Neuropsychiatric Division, Spedali Civili, Brescia, Italy. 6. Department of Child Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy. 7. Human Nutrition and Eating Disorders Research Centre, University of Pavia, Pavia, Italy. 8. Brain and Behaviour Department, University of Pavia, Pavia, Italy; Department of Child Neurology and Psychiatry, "C. Mondino" National Neurological Institute, Pavia, Italy. Electronic address: pveggiot@unipv.it.
Abstract
PURPOSE: GLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission. METHODS: We present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DS patients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation. RESULTS: We found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms. CONCLUSION: The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling.
PURPOSE:GLUT1deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission. METHODS: We present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DSpatients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation. RESULTS: We found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms. CONCLUSION: The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling.