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.
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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.
This study was funded partly by the German Network of ALS (BMBF 01GM1103A).
Conflicts of interest
The authors declare that they have no conflict of interest.
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
- Kennedy’s disease
- Spinobulbar muscular atrophy
- Motor neuron disease