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 |
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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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