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The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy

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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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Acknowledgements

We thank Nicola Laemmle for her excellent work as a study nurse and for her assistance with sample collection and Nayana Gaur for the critical reading of the manuscript.

Funding

This study was funded partly by the German Network of ALS (BMBF 01GM1103A).

Author information

Authors and Affiliations

  1. Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany

    Angela Rosenbohm, Susanne Hirsch, Hans-Peter Müller, Jochen Weishaupt, Jan Kassubek, Patrick Weydt & Albert C. Ludolph

  2. Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany

    Alexander E. Volk & Christian Kubisch

  3. Department of Neurology, Alfried Krupp Krankenhaus Rüttenscheid, Essen, Germany

    Torsten Grehl

  4. Department of Neurology, University of Jena, Jena, Germany

    Julian Grosskreutz

  5. Department of Neurology, University of Halle, Halle, Germany

    Frank Hanisch

  6. Department of Neurology and German Center for Neurodegenerative Diseases (DZNE), Research Site Dresden, Technische Universität Dresden, Dresden, Germany

    Andreas Herrmann

  7. Department of Neurology, Medical School Hannover, Hannover, Germany

    Katja Kollewe & Susanne Petri

  8. Institute of Human Genetics, University of Würzburg, Würzburg, Germany

    Wolfram Kress

  9. Department of Neurology, Outpatient Clinic for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Thomas Meyer

  10. Department of Neurology and German Center for Neurodegenerative Diseases (DZNE), Rostock University Medical Center, Rostock, Germany

    Johannes Prudlo

  11. Department of Neurology, Bavaria Clinic, Bad Kissingen, Germany

    Carsten Wessig

  12. Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany

    Jens Dreyhaupt

  13. Department of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn, Bonn, Germany

    Patrick Weydt

  14. Institute of Human Genetics, University of Ulm, Ulm, Germany

    Alexander E. Volk & Christian Kubisch

Authors
  1. Angela Rosenbohm
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  2. Susanne Hirsch
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  3. Alexander E. Volk
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  4. Torsten Grehl
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  5. Julian Grosskreutz
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  8. Katja Kollewe
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  9. Wolfram Kress
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  10. Thomas Meyer
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  11. Susanne Petri
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  13. Carsten Wessig
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  14. Hans-Peter Müller
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  15. Jens Dreyhaupt
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  16. Jochen Weishaupt
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  17. Christian Kubisch
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  18. Jan Kassubek
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  19. Patrick Weydt
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  20. Albert C. Ludolph
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Corresponding author

Correspondence to Albert C. Ludolph.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

All persons gave their informed consent prior to their inclusion in the study. The study was approved by the local ethics committee of the University of Ulm (73/10 and 92/10).

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Rosenbohm, A., Hirsch, S., Volk, A.E. et al. The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy. J Neurol 265, 1026–1036 (2018). https://doi.org/10.1007/s00415-018-8790-2

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  • DOI: https://doi.org/10.1007/s00415-018-8790-2

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