Hereditary spastic paraplegia type 11 (SPG11) is associated with obesity and hypothalamic damage

Abstract

SPG11 mutations lead to heterogeneous neurological phenotypes, but metabolic abnormalities have not yet been explored in this disease. In this study, we investigate whether SPG11 pathogenic variants might affect metabolic regulation, leading to weight changes and if this could relate to hypothalamic damage. In this cross-sectional case-control study, we selected a group of individuals with confirmed SPG11 mutations (n = 20), paired with healthy controls - both groups underwent brain MRI, from which we performed manual hypothalamic segmentation - and patients with Friedreich Ataxia (FRDA), having collected weight and height data for BMI-comparison. In the SPG11 group, we found significantly higher BMI compared to FRDA (p = .034), as well as hypothalamic atrophy compared to controls (p = .030). Volumetric changes were not associated with BMI, age, disease duration or SPRS amongst subjects with SPG11. Therefore, this study presents a new feature in SPG11 by characterizing a higher obesity rate in these patients, that could be associated with the hypothalamic atrophy found in this population.

Keywords: Body mass index; Hereditary spastic paraplegia; Hypothalamus; Lysossome.