X-linked myopathy with excessive autophagy: what it is, causes, symptoms, treatment

What is X-linked myopathy with excessive autophagy?

X-linked myopathy with excessive autophagy is an extremely rare genetic disorder characterized by muscle disease (myopathy). The disorder is fully expressed only in males and is characterized by slowly progressive muscle weakness, especially in the legs.

The onset usually occurs in childhood, often between 5-10 years of age. X-linked myopathy with excessive autophagy occurs due to mutations in an unidentified gene on the X chromosome. The disorder is inherited by an X-linked recessive trait.

Signs and symptoms

Symptoms of X-linked myopathy with excessive autophagy usually appear during childhood. The disorder is fully expressed only in men. Women with the defective gene do not develop any overt symptoms (i.e. asymptomatic) or only very mild symptoms are observed.

A key finding in this disease is slowly progressive muscle weakness, especially in the proximal muscles of the legs.

The proximal muscles are those closer to the center of the body (for example, the muscles of the upper leg).

As the disease progresses, some people may have difficulty performing certain activities, such as climbing stairs and running.

During the second decade of life, the muscles of the upper limbs or shoulders may be involved. In some cases, muscles away from the center of the body (distal muscles), such as the muscles in the arms and legs, may be involved.

In adulthood, muscle degeneration may occur (amyotrophy). Some people may need a wheelchair by the age of six.

According to the medical literature, X-linked myopathy with excessive autophagy is not associated with involvement of other organ systems.

Causes of occurrence

X-linked myopathy with excessive autophagy is inherited as an X-linked recessive disorder. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome.

Women have two X chromosomes, but one of the X chromosomes is turned off and all genes on that chromosome are inactivated. Women who have a disease gene on one of their X chromosomes are carriers of the disorder. Carrier women usually do not show symptoms of the disorder because usually the X chromosome with the abnormal gene is turned off. A man has one X chromosome, and if he inherits the X chromosome containing the disease gene, he will develop the disease. Men with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A man cannot pass the X-linked gene to his sons because men always pass on their Y chromosome instead of their X chromosome to male offspring.

The researchers found that this disease occurs due to a violation or change (mutation) of an unidentified gene located on the long arm (q) of the X chromosome (Xq28). Chromosomes, which are present in the nucleus of human cells, carry the genetic information of each person. Pairs of human chromosomes are numbered 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm, labeled "p", and a long arm, labeled "q". Chromosomes are further subdivided into multiple bands, which are numbered. For example, "chromosome Xq28" refers to lane 28 on the long arm of the X chromosome. The numbered stripes indicate the location of the hundreds of genes that are present on each chromosome.

Unlike similar muscle disorders, X-linked myopathy with excessive autophagy rarely shows death (necrosis) of muscle tissue when examined under a microscope. However, the muscle tissue of people with this condition exhibits excessive autophagy. Autophagy is a normal process in which cell components are destroyed and reused, often during times of stress or hunger.

Autophagy also plays a role in the body's defense against foreign or invading substances, serving as a second line of defense after the immune system. Although people with this disease exhibit excessive autophagy in muscle tissue, the exact role or significance of this finding in relation to the development and progression of the disease is unknown.

Affected populations

X-linked myopathy with excessive autophagy has been reported in only about 20 families. It is only fully expressed in men, although women may also develop mild symptoms.

Because this disorder is often unrecognized, it can go undiagnosed, making it difficult to determine its true frequency in the general population.

X-linked myopathy with excessive autophagy was first described in the medical literature in 1988.

Similar disorders

Symptoms of the following disorders may be similar to those of this disease. Comparisons can be useful for differential diagnosis.

Danone's disease is a rare genetic multisystem disorder characterized by a triad of muscle disorders (myopathy), an abnormal thickening of the heart walls leading to obstruction of blood flow to and from the heart (hypertrophic cardiomyopathy), and in some cases, moderate mental retardation.

The disorder is fully expressed only in men, although women may have some symptoms, especially heart problems. In some cases, heart abnormalities can lead to life-threatening complications. Muscle disease in Danone disease is similar to that found in X-linked myopathy with excessive autophagy.

Danone disease is inherited as X-linked. The gene responsible for the disorder is located on the long arm (q) of the X chromosome (Xq24).

Emery-Dreyfus muscular dystrophy is a rare, often slowly progressive form of muscular dystrophy that affects the muscles of the arms, legs, face, neck, spine, and heart. The disorder consists of the clinical triad of weakness and degeneration (atrophy) of certain muscles, joints that are fixed in a flexed or extended position (contractures), and pathologies affecting the heart (cardiomyopathy).

Major symptoms can include muscle wasting and weakness, especially in the upper legs and arms (shoulder areas), and contractures of the elbows, Achilles tendons, and upper back muscles. In some cases, additional violations may be present.

Emery-Dreyfus muscular dystrophy is inherited as an X-linked, autosomal dominant, or autosomal recessive trait.

Muscular dystrophy of the limbs - a group of rare muscle disorders. At least 10 different disorders are included in this group. In most cases, the muscles around the thighs and shoulder girdle are affected first. Most of these disorders are inherited as an autosomal recessive trait.

Symptoms of muscular dystrophy of the extremities usually appear in childhood or adolescence as pelvic muscle weakness. Weakness of the shoulder, which can lead to loss of mobility, usually occurs over the next 20 to 30 years. Additional muscles may also be involved in the development of the disorder.

Diagnostics

Diagnosis is based on careful clinical evaluation, the patient's detailed medical history, and surgical removal and microscopic evaluation (biopsy) of the affected muscle tissue.

Standard treatments

There is no specific therapy for X-linked myopathy with excessive autophagy. Treatment focuses on the specific symptoms that each person experiences. In some cases, people aged 60 and over may end up becoming wheelchair dependent.

Genetic counseling can be beneficial for affected individuals and their families. Other treatments are symptomatic and supportive.