Clinical Phenotyping and Biomarkers in Spinal and Bulbar Muscular Atrophy

Elina Millere; Dmitrijs Rots; Ieva Glazere; Gita Taurina; Natalja Kurjane; Viktorija Priedite; Linda Gailite; Kaj Blennow; Henrik Zetterberg; Viktorija Kenina

doi:10.3389/fneur.2020.586610

Clinical Phenotyping and Biomarkers in Spinal and Bulbar Muscular Atrophy

Front Neurol. 2021 Jan 20:11:586610. doi: 10.3389/fneur.2020.586610. eCollection 2020.

Authors

Elina Millere^{1

2

3}, Dmitrijs Rots³, Ieva Glazere^{4

5}, Gita Taurina⁶, Natalja Kurjane^{5

7}, Viktorija Priedite⁸, Linda Gailite³, Kaj Blennow^{9

10}, Henrik Zetterberg^{9

10

11

12}, Viktorija Kenina^{5

13}

Affiliations

¹ Department of Neurology and Neurosurgery, Children's Clinical University Hospital, Riga, Latvia.
² Department of Doctoral Studies, Riga Stradins University, Riga, Latvia.
³ Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia.
⁴ Department of Neurology, Pauls Stradins Clinical University Hospital, Riga, Latvia.
⁵ Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.
⁶ Department of Medical Genetics and Prenatal Diagnostics, Children's Clinical University Hospital, Riga, Latvia.
⁷ Outpatient Service Centre, Pauls Stradins Clinical University Hospital, Riga, Latvia.
⁸ BIOCON Medical Laboratory, LCC BIOCON, Riga, Latvia.
⁹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, United Kingdom.
¹² UK Dementia Research Institute at University College London, London, United Kingdom.
¹³ Rare Disease Centre, Riga East Clinical University Hospital, Riga, Latvia.

Abstract

Background: Spinal and bulbar muscular atrophy (SBMA) or Kennedy disease [OMIM: 313200] is a rare X-linked neuromuscular disease. Patients commonly present with muscle cramps, tremors, leg weakness, dysarthria and dysphagia. Methods: We deeply phenotyped and evaluated the possible extent of affected systems in all patients with SBMA in Latvia (n = 5). In addition, neurophysiological studies and blood analyses were used to perform a molecular diagnosis and evaluate biochemical values. We analyzed neurofilament light (NfL) as a possible biomarker. Results: Neurological examination revealed typical SBMA clinical manifestations; all patients had small or large nerve fiber neuropathy. Three of five patients had increased neurofilament light levels. Conclusion: The study confirms the systemic involvement in patients suffering from SBMA. Increased NfL concentration was associated with either peripheral neuropathy or decreased body mass index. The complex phenotype of the disease should be kept in mind, as it could help to diagnose patients with SBMA.

Keywords: Kennedy disease; biomarker; clinical features; neurofilament; phenotype; spinal and bulbar muscular atrophy.