Clinical Phenotyping and Biomarkers in Spinal and Bulbar Muscular Atrophy

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.

Clinical spectrum, biochemical profile and disease progression of Kennedy disease in an Indian cohort

“…13 Previous studies showed that non-specific features like cramps, myalgia and fatigue precede the appearance of motor symptoms. 6,7 However, all of our patients most commonly had motor symptoms at the onset along with non-specific symptoms. Early prominent hand tremor was noted in five patients, with initial diagnosis as essential tremors in one patient (P6).…”

“…Other non-specific symptoms, such as muscle cramps, myalgia, excessive fatigability and postural hand tremors, tend to occur earlier than the typical motor features. 6,7 KD is a multisystem disorder with metabolic derangements, such as impaired glucose tolerance, dyslipidemia, thyroid dysfunction, gynaecomastia, erectile dysfunction and loss of libido. 8 Prevalence of KD is unknown in India due to its rarity, lack of awareness among neurologists and its overlapping features with amyotrophic lateral sclerosis (ALS).…”

“…Additional neurological manifestations include peripheral neuropathy and autonomic dysfunction. Other non‐specific symptoms, such as muscle cramps, myalgia, excessive fatigability and postural hand tremors, tend to occur earlier than the typical motor features 6,7 . KD is a multisystem disorder with metabolic derangements, such as impaired glucose tolerance, dyslipidemia, thyroid dysfunction, gynaecomastia, erectile dysfunction and loss of libido 8 …”

Tremor Syndromes: An Updated Review

“…Spinal and bulbar muscular atrophy or Kennedy disease, a rare X-linked neuromuscular disease caused by a CAG repeat expansion in the first exon of the androgen receptor gene, is manifested by bulbar symptoms, muscle cramps, leg weakness, and tremor ( 173 ). The patients have evidence of small or large nerve fiber neuropathy and, therefore, the observed tremor may be a neuropathic tremor.…”

Perlas Clínicas en Neurología

“…La atrofia muscular espinal y bulbar o enfermedad de Kennedy, una rara enfermedad neuromuscular ligada al cromosoma X causada por una expansión repetida de CAG en el primer exón del gen del recTPEor de andrógenos, se manifiesta por síntomas bulbares, calambres musculares, debilidad en las piernas y temblores ( 173 ). Los pacientes tienen evidencia de neuropatía de fibra nerviosa pequeña o grande y, por lo tanto, el temblor observado puede ser un temblor neuropático.…”