Neurology: clinical features of female carriers and prodromal male patients with spinal muscular atrophy

Spinal cord and medullary muscular atrophy (SBMA) is an adult-onset X-linked recessive neuromuscular disorder
.
SBMA is caused
by expansion of trinucleotide CAG repeats within the first exon of the androgen receptor (AR) gene.
The main symptoms are muscle atrophy, weakness of the extremities, and contraction of the muscles of the face, medulla oblongata, and limbs, manifested between
the ages of 30 and 60 years.
CAG repeats are age-dependent and similar to
other glutamine disorders.
Electrophysiologic studies show decreased motor and sensorineural action potentials and motility estimation (MUNE), reflecting motor neuron degeneration and correlated
with CAG repeats.

A study published in Neurology explored the clinical and electrophysiological features of spinal and medullary muscular atrophy (SBMA) in female carriers and early men to elucidate the early pathophysiological changes
of the disease.

Female carriers, early male SBMA subjects, and age-matched male and female healthy controls were recruited
.
Results of the Motor Function Scale, comparing exercise estimates, dual-energy x-ray absorbers, and peripheral blood tests
between female carriers and healthy female controls, and between SBMA subjects and healthy male controls.
Electromyography has also been studied
in female carriers.

Studies recruited 21 female carriers and 11 early male participants
.
Seventeen female and 14 male age-matched healthy controls were also included
.
Female carriers experienced early symptoms such as muscle cramps more
frequently than healthy female controls.
Female carriers are estimated to have reduced the number of movements, and EMG abnormalities include high amplitude or polyphasic potentials, weakness of neck flexion muscles, and slow
walking speed.
Changes in muscle-related markers, including serum creatine kinase and dual-energy x-ray absorptiometry, are evident in men with early SBMA but not
in female carriers.

This study found that female carriers of SBMA showed mild muscle weakness, which was associated with
alterations in neurogenic biomarkers.
In contrast, male patients show neurogenic and myopathic changes
even in the early stages.
These results suggest a neurodegenerative pathophysiology
independent of testosterone in female SBMA carriers.

Sources:

Torii R, Hashizume A, Yamada S, et al.
Clinical Features of Female Carriers and Prodromal Male Patients With Spinal and Bulbar Muscular Atrophy [published online ahead of print, 2022 Sep 30].
Neurology.
2022; 10.
1212/WNL.
0000000000201342.
doi:10.
1212/WNL.
0000000000201342