The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy

Autor: Andreas Herrmann, Angela Rosenbohm, Christian Kubisch, Hans-Peter Müller, Thomas Meyer, Katja Kollewe, Torsten Grehl, Patrick Weydt, Jan Kassubek, Susanne Hirsch, Wolfram Kress, Jochen H. Weishaupt, Frank Hanisch, Albert C. Ludolph, Carsten Wessig, Johannes Prudlo, Susanne Petri, Alexander E Volk, Jens Dreyhaupt, Julian Grosskreutz
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Physiology
diagnostic imaging [Muscular Atrophy
Spinal]
genetics [Muscular Atrophy
Spinal]
chemistry.chemical_compound
0302 clinical medicine
Sex hormone-binding globulin
Medicine
Glucose homeostasis
Aged
80 and over
blood [Biomarkers]
biology
Middle Aged
Magnetic Resonance Imaging
metabolism [Glucose]
Adipose Tissue
Neurology
Body Composition
Disease Progression
Biomarker (medicine)
medicine.symptom
metabolism [Muscular Atrophy
Spinal]
Adult
medicine.drug_class
Muscular Atrophy
Spinal
03 medical and health sciences
Dehydroepiandrosterone sulfate
metabolism [Hormones]
Humans
ddc:610
Muscle
Skeletal
Aged
physiopathology [Muscle
Skeletal]
business.industry
Muscle weakness
Lipid Metabolism
Androgen
medicine.disease
Hormones
Spinal and bulbar muscular atrophy
Glucose
030104 developmental biology
chemistry
diagnostic imaging [Adipose Tissue]
biology.protein
Neurology (clinical)
Trinucleotide Repeat Expansion
Trinucleotide repeat expansion
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: Journal of neurology 265(5), 1026-1036 (2018). doi:10.1007/s00415-018-8790-2
ISSN: 1432-1459
0340-5354
Popis: Spinal and bulbar muscular atrophy (SBMA) is caused by an abnormal expansion of the CAG repeat in the androgen receptor gene. This study aimed to systematically phenotype a German SBMA cohort (n = 80) based on laboratory markers for neuromuscular, metabolic, and endocrine status, and thus provide a basis for the selection of biomarkers for future therapeutic trials. We assessed a panel of 28 laboratory parameters. The clinical course and blood biomarkers were correlated with disease duration and CAG repeat length. A subset of 11 patients was evaluated with body fat MRI. Almost all patients reported muscle weakness (99%), followed by dysphagia (77%), tremor (76%), and gynecomastia (75%) as major complaints. Creatine kinase was the most consistently elevated (94%) serum marker, which, however, did not relate with either the disease duration or the CAG repeat length. Paresis duration and CAG repeat length correlated with dehydroepiandrosterone sulfate after correction for body mass index and age. The androgen insensitivity index was elevated in nearly half of the participants (48%). Metabolic alterations in glucose homeostasis (diabetes) and fat metabolism (combined hyperlipidemia), and sex hormone abnormalities (androgen insensitivity) could be observed among SBMA patients without association with the neuromuscular phenotype. Dehydroepiandrosterone sulfate was the only biomarker that correlated strongly with both weakness duration and the CAG repeat length after adjusting for age and BMI, indicating its potential as a biomarker for both disease severity and duration and, therefore, its possible use as a reliable outcome measure in future therapeutic studies.
Databáze: OpenAIRE
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