title: A 23 years follow-up study identifies GLUT1 deficiency syndrome initially diagnosed as complicated hereditary spastic paraplegia.
abstract: Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) was initially described in the early 90s as a sporadic clinical condition, characterized by seizures, motor and intellectual impairment with variable clinical presentation, and without a known genetic cause. Although causative mutations in SLC2A1 were later identified and much more is known about the disease, it still remains largely underdiagnosed. In the current study, a previously described Italian family was re-analyzed using whole exome sequencing and clinically re-evaluated. Affected individuals presented with spastic paraplegia as a predominant symptom, with epilepsy and intellectual disability, inherited as an autosomal dominant trait with variable clinical presentation. While a novel variant of hereditary spastic paraplegia (HSP) was initially hypothesized in this family, previous linkage studies of known HSP genes did not identify the genetic cause. Exome-sequencing study identified a p.Arg126Cys mutation in the SLC2A1 gene, encoding GLUT1, which segregated with the affected members of the family. The diagnosis of GLUT1DS was further confirmed by cerebrospinal fluid analysis, and treatment was started with good initial response. The description of this large family provides further clinical information on this rare disease. It also offers an example of how GLUT1DS can be challenging to diagnose, and emphasizes the importance of lumbar puncture in the workflow of similar syndromes. Finally, it suggests that analysis of SLC2A1 should be considered in the diagnostic work up of HSP, especially if it is associated with epilepsy.
authors.affiliation: Neurological Clinic, Department of Systems Medicine, Tor Vergata University, Rome, Italy. Electronic address: marina.diomedi@uniroma2.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Diomedi
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Departments of Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gan-Or
authors.affiliation: Neurological Clinic, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Placidi
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Departments of Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Szuto
authors.affiliation: Medical Genetic Laboratories, Tor Vergata University Hospital, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bengala
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Departments of Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.affiliation: Neurology, Department of Experimental and Clinical Medical Sciences, University of Udine Medical School and Department of Neurosciences, ''S. Maria della Misericordia'' University Hospital, Udine, Italy.
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gigli
mesh_terms: D000293:Adolescent; D000328:Adult; D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human
keywords: Epilepsy; GLUT1 deficiency syndrome; Hereditary spastic paraplegia; SLC2A1; Spasticity