Metabolism plays an important role in neurodegenerative diseases. Hereditary spastic paraplegias (HSP) are a heterogeneous group of rare genetic neurodegenerative disorders, commonly characterized by the clinical syndrome of progressive lower limb spasticity and mobility loss. Obesity has been linked to distinct genotypes, but the role of metabolism and nutrition in HSP remains unclear.We aimed to To evaluate metabolism and nutrition in specific HSP genotypes and to assess the impact of nutritional counseling on disease progression and body composition. In this prospective explorative pilot study, we assessed the neurological, metabolic and nutritional status of patients with HSP at baseline and one year after nutritional counseling. A total of 36 patients with genetically confirmed SPG4-, SPG7- and SPG11-associated HSP were recruited. BMI in SPG4 and SPG7 was comparable to healthy population data, whereas SPG11 showed significantly higher BMI (+ 22.9%, p < 0.05) with a considerable interindividual variability. Across all genotypes, disease severity according to the Spastic Paraplegia Rating Scale correlated negatively with leg muscle mass (ρ = -0.39, p < 0.05), protein (ρ = -0.35, p < 0.05) and fiber intake (ρ = -0.41, p < 0.05). After one year, there was a significant loss of relative muscle mass (-7.2%, p < 0.001). Progressive loss of muscle mass in HSP asks for an effective nutritional intervention combined with exercise in order to influence disease progression in HSP. The SPG11-associated obese phenotype may evolve with disease progression due to multifactorial metabolic changes, beyond reduced mobility.
Erhardt et al. (Tue,) studied this question.