SLC2A1 mutations are a rare cause of pediatric-onset hereditary spastic paraplegia

Abstract

SLC2A1 mutations cause glucose transporter type 1 deficiency syndrome, whose phenotypic spectrum is a continuum, ranging from classic to variant phenotypes, the latter accounting for about 10% of cases. Very few SLC2A1-mutated patients with a spastic paraplegia phenotype have been reported so far, and they are associated with paroxysmal choreo-athetosis (i.e., DYT9). The authors describe two sporadic children with pure and complex hereditary spastic paraplegia (HSP) without paroxysmal non-epileptic movement disorders harboring heterozygous de novo SLC2A1 pathogenic variants. These patients have been identified by a targeted panel for HSP among 140 pediatric- and adult-onset unrelated cases with pure and complex HSP, thus indicating an overall prevalence of 1.4% of SLC2A1 mutations, which increases to 3% if only pediatric-onset patients are considered. The implications of these findings in the diagnostic work-up of HSP patients are discussed.

Keywords: Ataxia; DYT18; DYT9; GLUT1; Hereditary spastic paraparesis; Paroxysmal choreo-atethosis.