Metabolic alterations in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is a rare, X-linked neuromuscular disease characterised by lower motor neurons degeneration, slowly progressive myopathy and multisystem involvement. SBMA is caused by trinucleotide repeat expansion in the first exon of the androgen receptor (AR) gene on chromosome X that encodes a polyglutamine (polyQ) tract in the AR protein. Disease onset occurs between 30-60 years of age with easy fatigability, muscle cramps, and weakness in the limbs. In addition to neuromuscular involvement, in SBMA phenotype, many non-neural manifestations are present. Recently, some studies have reported a high prevalence of metabolic and liver disorders in patients with SBMA. Particularly, fatty liver and insulin resistance (IR) have been found in many SBMA patients. The alteration of AR function and the androgen insensitivity can be involved in both fatty liver and IR. In turn, IR and liver alterations can influence neuromuscular damage through different mechanisms. These data lead to consider SBMA as a metabolic as well as a neuromuscular disease. The mechanism of metabolic alterations, their link with the neuromuscular damage, the effects on the course of disease and their treatment will have to be yet fully clarified. (C) 2020 Elsevier Masson SAS. All rights reserved.