Clinical features of spinal and bulbar muscular atrophy

Abstract

Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models.

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy

“…Androgen insensitivity mainly shows gynecomastia, hypogonadism, and reduced fertility (azoospermia, oligospermia) [30,31]. Patients with SBMA usually present muscle weakness in their midforties [32]. However, the age of disease onset correlates inversely with the CAG repeat length, i.e., greater CAG repeat lengths correspond to earlier disease onset [29].…”

Pearls & Oy-sters: HyperCKemia with limb-girdle weakness

“…1 Associated neurologic symptoms include muscle cramps, tremor, and varying degrees of sensory loss. 1 Signs of androgen resistance (gynecomastia, erectile dysfunction, and reduced fertility), glucose intolerance, and diabetes mellitus are often present. 1 Recently, Brugada-like ECG abnormalities were also described in patients with SBMA.…”

“…1 Signs of androgen resistance (gynecomastia, erectile dysfunction, and reduced fertility), glucose intolerance, and diabetes mellitus are often present. 1 Recently, Brugada-like ECG abnormalities were also described in patients with SBMA. 2 SBMA is caused by CAG-polyglutamine repeat expansion within the exon 1 of AR.…”

“…4 The X-linked recessive inheritance of SBMA is also helpful for the diagnosis, though family history is apparent in only about 50%-68% of the cases. 1,4 The main clinical distinction between ALS and SBMA is the absence of upper motor neuron involvement in SBMA. Predominant proximal or less commonly predominant distal weakness would favor the diagnosis of SMA (SMA3 and DSMA3, respectively).…”

Effect of Age, Cartilage Health and Pain on the Isometric Strength of Knee Musculature: A Cross-Sectional Study

“…Cable tensiometer has been used in the number of previous studies to measure isometric strength of both upper limb as well as lower limb musculatures [19][20][21][22]. Previous studies have found the effect of aging on the muscle strength.…”