X-linked spinal muscular atrophy 2

X-linked spinal muscular atrophy 2 (XL-SMA2) is a rare genetic disorder characterized by progressive muscle weakness and atrophy. It is a type of spinal muscular atrophy (SMA), a group of hereditary diseases that cause progressive degeneration of the motor neurons in the spinal cord.

Etiology

XL-SMA2 is caused by mutations in the UBA1 gene, which is located on the X chromosome. This gene provides instructions for making a protein that is involved in the degradation of damaged or unnecessary proteins within cells. Mutations in the UBA1 gene disrupt this process, leading to the accumulation of abnormal proteins that can damage cells. This is particularly harmful to motor neurons, which are highly sensitive to changes in their environment.

Symptoms

The symptoms of XL-SMA2 typically begin in infancy or early childhood. They include progressive muscle weakness, particularly in the muscles closest to the center of the body (proximal muscles), such as those of the hips, thighs, shoulders, and upper arms. Affected individuals may also have difficulty swallowing (dysphagia) and breathing, and may develop a curved spine (scoliosis) as a result of muscle weakness.

Diagnosis

Diagnosis of XL-SMA2 is based on the observation of characteristic symptoms, a family history of the disorder, and genetic testing to identify mutations in the UBA1 gene. Other tests, such as electromyography (EMG) and nerve conduction studies, may be used to assess the extent of nerve damage.

Treatment

There is currently no cure for XL-SMA2, and treatment is focused on managing symptoms and improving quality of life. This may include physical therapy to maintain mobility and prevent contractures, respiratory therapy to manage breathing difficulties, and nutritional support to address swallowing difficulties. In some cases, surgery may be necessary to treat scoliosis or other complications.

Prognosis

The prognosis for individuals with XL-SMA2 varies depending on the severity of symptoms. Some individuals may have a normal lifespan with mild disability, while others may experience severe disability and life-threatening complications.

See also

• Spinal muscular atrophy
• X-linked recessive inheritance
• UBA1