26. Kongress des Medizinisch-Wissenschaftlichen Beirates der Deutschen Gesellschaft für Muskelkranke (DGM) e.V.

PD Dr.

Vorsitz

X- chromosomale neuromuskuläre Erkrankungen - ist es Zeit für eine Änderung von Überträgerin zu Patientin?

Dr. med.

eingeladener Redner

Vortrag

Carrierinnen bei X-chromosomalen Erkrankungen am Beispiel der myotubulären Myopathie

Prof. Dr.

Prof.

Prof. Dr. med.

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.

Biomarker - molekular, klinisch, digital

Diagnostische Verfahren

Freier Vortrag

Identification of a disease signature for premotor and early ALS.

Abstract-Text (inkl. Referenzen) Introduction: Amyotrophic lateral sclerosis (ALS) is the most common motoneuron disease with a long diagnostic delay. Because of the rapid and fatal progression of ALS, early diagnosis is crucial to start therapy early and allow for inclusion in clinical trials. About 10% of ALS patients have a genetic cause. Genetic testing of their family members can identify subjects, who carry the mutation, but have not yet developed symptoms of the disease, so-called "pre-symptomatic gene mutation carriers" (PGMC). We aim to identify early ALS biomarkers already present in PGMC. Method: For this study, 10 different countries join forces (Germany, France, Switzerland, Turkey, Slovakia, Israel, Sweden, Poland, Australia and USA). PGMC, control subjects and patients with suspicion for ALS (n=110 per group) will be recruited and longitudinally assessed over one year. Assessments include a medical history questionnaire, neurological examination, and the collection of biological samples (serum, plasma, urine, tear fluid, and CSF). Proteomic and metabolomic profiles will be analyzed by mass spectrometry and targeted immunoassays. Results: The &quot;premodiALS&quot;-study secured funding within the JPND-call 2021 and received ethical approval. Recruitment will start in Q1/2023. Discussion: A clinical and molecular ALS fingerprint would improve the timeliness and accuracy of diagnosis of ALS and ultimately lead to more effective treatment strategies.

Sitzung 2
Carrier: Patient oder nicht?

Appointment

Vorsitz

Programme

Sitzung 2Carrier: Patient oder nicht?

Appointment

Vorsitz

Programme

Sitzung 2
Carrier: Patient oder nicht?