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20.02.2018 | Original Communication

The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy

verfasst von: Angela Rosenbohm, Susanne Hirsch, Alexander E. Volk, Torsten Grehl, Julian Grosskreutz, Frank Hanisch, Andreas Herrmann, Katja Kollewe, Wolfram Kress, Thomas Meyer, Susanne Petri, Johannes Prudlo, Carsten Wessig, Hans-Peter Müller, Jens Dreyhaupt, Jochen Weishaupt, Christian Kubisch, Jan Kassubek, Patrick Weydt, Albert C. Ludolph

Erschienen in: Journal of Neurology | Ausgabe 5/2018

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Abstract

Objective

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.

Methods

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.

Results

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%).

Conclusions

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.

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Titel: The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy
verfasst von: Angela Rosenbohm
Susanne Hirsch
Alexander E. Volk
Torsten Grehl
Julian Grosskreutz
Frank Hanisch
Andreas Herrmann
Katja Kollewe
Wolfram Kress
Thomas Meyer
Susanne Petri
Johannes Prudlo
Carsten Wessig
Hans-Peter Müller
Jens Dreyhaupt
Jochen Weishaupt
Christian Kubisch
Jan Kassubek
Patrick Weydt
Albert C. Ludolph
Publikationsdatum: 20.02.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 5/2018
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-8790-2

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