TY  - JOUR
AU  - Xia, Kailin
AU  - Witzel, Simon
AU  - Witzel, Christina
AU  - Klose, Veronika
AU  - Fan, Dongsheng
AU  - Ludolph, Albert C
AU  - Dorst, Johannes
TI  - Mutation-specific metabolic profiles in presymptomatic amyotrophic lateral sclerosis.
JO  - European journal of neurology
VL  - 30
IS  - 1
SN  - 1351-5101
CY  - Oxford
PB  - Blackwell Science
M1  - DZNE-2022-01565
SP  - 87-95
PY  - 2023
N1  - ISSN 1468-1331 not unique: **2 hits**.
AB  -  Growing evidence shows that ALS patients feature a disturbed energy metabolism. However, these features have rarely been investigated in the presymptomatic stage.A total of 60 presymptomatic ALS mutation carriers and 70 age- and gender-matched controls (non-mutation carriers from the same families) were recruited. All subjects underwent assessments of their metabolic profiles under fasting conditions at enrollment, including body mass index (BMI), blood pressure and serum levels of blood glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein.All mutations combined, no differences between presymptomatic ALS gene carriers and controls were found. From a cardiovascular point of view, presymptomatic chromosome 9 open reading frame 72 (C9ORF72) gene carriers showed lower cardiovascular risk profiles compared to healthy controls, including lower BMI (median 22.9, interquartile range [IQR] 20.6-26.1 kg/m2 vs. 24.9, IQR 22.7-30.5 kg/m2 ; p = 0.007), lower systolic blood pressure (120, IQR 110-130 mmHg vs. 128, IQR 120-140 mmHg; p = 0.02), lower fasting serum glucose (89.0, IQR 85.0-97.0 mg/dl vs. 96.0, IQR 89.3-102.0 mg/dl; p = 0.005) and higher HDL (1.6, IQR 1.3-1.8 mmol/l vs. 1.2, IQR 1.0-1.4 mmol/l; p = 0.04). However, presymptomatic superoxide dismutase 1 (SOD1) gene mutation carriers showed higher cardiovascular risk profiles compared to healthy controls, including higher BMI (28.0, IQR 26.1-31.5 kg/m2 vs. 24.9, IQR 22.7-30.5 kg/m2 ; p = 0.02), higher fasting serum glucose (100.0, IQR 94.0-117.0 mg/dl vs. 96.0, IQR 89.3-102.0 mg/dl; p = 0.04) and lower HDL (1.2, IQR 1.0-1.4 mmol/l vs. 1.4, IQR 1.2-1.7 mmol/l; p = 0.01). These features were most prominent in patients carrying SOD1 gene mutations associated with slow disease progression.This study identified distinct metabolic profiles in presymptomatic ALS gene carriers, which might be associated with disease progression in the symptomatic phase.
KW  - Humans
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Superoxide Dismutase-1: genetics
KW  - Blood Glucose
KW  - Disease Progression
KW  - Metabolome
KW  - Amyotrophic lateral sclerosis (Other)
KW  - Genetics (Other)
KW  - Metabolism (Other)
KW  - Presymptomatic Gene Carriers (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36169607
DO  - DOI:10.1111/ene.15584
UR  - https://pub.dzne.de/record/165272
ER  -