# Heterogeneous phenotype and cardiovascular comorbidities in Swedish patients with spinobulbar muscular atrophy

## TL;DR

This study explores the varied symptoms and cardiovascular issues in Swedish patients with spinobulbar muscular atrophy, highlighting the need for better clinical awareness and monitoring.

## Contribution

The study identifies a high prevalence of cardiovascular comorbidities and sensory symptoms preceding motor decline in SBMA patients.

## Key findings

- 19% of patients initially presented with sensory symptoms before motor decline.
- Cardiovascular disease and diabetes were common comorbidities in the SBMA cohort.
- Elevated pNfL levels were observed in seven patients, indicating cerebrovascular and cardiovascular comorbidities.

## Abstract

Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by adult-onset progressive muscle atrophy, flaccid paresis, and bulbar palsy. In addition, increasing evidence indicates that SBMA is a multisystem disorder with prominent non-motor symptoms, such as sensory neuropathy, androgen insensitivity, and glucose intolerance. This study aimed to further characterize the clinical manifestations and biomarker profile in a large Swedish SBMA cohort.

49 genetically confirmed SBMA patients were identified from a motor neuron disease database at Umeå University Hospital, Sweden. CAG repeat length in the androgen receptor (AR) gene was assessed by RP-PCR. Blood samples were analyzed for cardiovascular and muscle biomarkers. Clinical data were collected from medical records and interviews, with autopsy findings reviewed in two cases.

The mean CAG repeat length was 43.1, with a mean age at motor symptom onset of 58.6 years. Notably, 19% of patients initially presented with sensory symptoms. High prevalence of hypertonia (70%), diabetes mellitus (39%), and cardiac disease (38%) was observed. Elevated troponin levels were common, and pNfL (neurofilament light chain in plasma) was elevated in seven patients, likely reflecting combined cerebrovascular and cardiovascular comorbidity. Importantly, two of these seven patients exhibited rapid disease progression, and a concomitant diagnosis of ALS was confirmed histopathologically.

This cohort was characterized by a relatively low number of AR gene CAG repeats and a late onset of motor symptoms. Sensory symptoms frequently occurred before motor decline. Cardiovascular disease and diabetes were common comorbidities and, in some cases, preceded neurological symptoms. These findings underscore the need for improved clinical awareness of the heterogeneous presentation of SBMA and support routine cardiovascular monitoring to reduce diagnostic delays and prevent early mortality.

The online version contains supplementary material available at 10.1007/s00415-025-13605-z.