Metabolische Veränderungen bei präsymptomatischen ALS-Genträgern

Abstract-Text (inkl. Referenzen)

Introduction

We sought to investigate whether metabolic alterations are detectable in presymptomatic ALS gene mutation carriers, and whether such alterations precede neurofilament light chain (NfL) changes.

Method

Between 02/2014 and 11/2021, we prospectively performed bioimpedance analysis and indirect calorimetry in 60 presymptomatic ALS gene mutation carriers (40% male, age 48.7 ± 14.9; 28 C9orf72, 22 SOD1, 10 other) compared to 73 individuals from the same families (47% male, age 47.4 ± 12.9) without pathogenic mutations as controls.

Results

Presymptomatic ALS gene carriers showed reduced Phase Angle (p=0.04) and increased Extracellular Mass/Body Cell Mass (ECM/BCM) ratio (p=0.04), indicating a loss of metabolically active body cells. While in C9orf72 mutation carriers all tissue masses were reduced, only metabolically active tissue was affected in SOD1 mutation carriers. Metabolic Rate (p=0.01) was reduced in presymptomatic ALS gene carriers (r=-0.40, p=0.004), while neurofilaments were still normal (p=0.60).

Interpretation

The observed metabolic phenomena might reflect reduced physical activity and/or preemptive, insufficient compensatory mechanisms to prepare for the later hypermetabolic state. ECM/BCM ratio and Phase Angle may serve as new biomarkers for genetic ALS to facilitate earlier diagnosis and treatment with antisense oligonucleotides.