What Is Adrenomyeloneuropathy?
An inherited condition affecting the spinal cord is known as adrenomyeloneuropathy (AMN). Adrenomyeloneuropathy is an adult variant of X-linked adrenoleukodystrophy. It is marked by ABCD1 gene mutation, which is linked in an X-linked manner, resulting in the deformed peroxisomal function with the long-chain fatty acids accumulation and demyelination.
People with this disease begin to see the symptoms in their thirties. The signs and symptoms include progressive stiffness of the legs, weakness of the legs, lack of muscle control, adrenal insufficiency, difficulty in speaking, sexual dysfunction, and urinary incontinence. In addition, it may lead to blurred vision, seizures, and behavioral abnormalities, as it is also associated with the brain. The treatment will depend on the clinical manifestations and differ in each person.
What Are the Causes of Adrenomyeloneuropathy?
The exact cause of adrenomyeloneuropathy is the change (mutation) in the ABCD1 gene. This gene is linked in an X-linked manner which delivers the body instructions to make a protein, namely adrenoleukodystrophy protein (ALDP). This protein is helpful to transport certain body fats known as very long-chain fatty acids into the peroxisomes, which contain enzymes to perform metabolic reactions. Peroxisomes are enclosed organelles in cells that are used to break down fats and other substances into energy.
Mutations in this ABCD1 gene may result in low levels of adrenoleukodystrophy protein, resulting in increased levels of long-chain fatty acids. An increase in the level of fatty acids in the adrenal gland, nervous system, and testes may disrupt their normal function and result in the signs and symptoms of adrenomyeloneuropathy.
Inheritance:
Adrenomyeloneuropathy is acquired genetically in an X-linked manner. When the reliable gene is found to be on the X chromosome, which is one of the two sex chromosomes, the condition is considered X-linked. The other sex chromosome is the Y chromosome, where men have an X and Y chromosome and women have two X chromosomes.
As men have one X and Y chromosome, the responsible gene gets mutated, and the copy of these mutated genes in each cell is sufficient to produce signs and symptoms of the condition. When a man has inherited an X-linked condition, he will pass the mutated gene to all of his daughters but not his sons.
Women have two X chromosomes, and if one X chromosome gets mutated, its effect will be masked by the healthy copy of the gene within the other X chromosome. A woman is said to be a carrier of an X-linked condition if only one X chromosome gets mutated. Most carrier women are mildly affected and will not exhibit any symptoms. Women with X-linked conditions will have a 50 % chance of passing the mutation on each pregnancy. However, some women may get severely affected as males and produce signs and symptoms.
Approximately 20 % of women with adrenomyeloneuropathy who carry one ABCD1 mutation will start developing weakness and progressive stiffness in their legs in their middle age. The positive note is that these women have a normal adrenal function.
What Are the Symptoms of Adrenomyeloneuropathy?
Adrenomyeloneuropathy is a type of X-linked adrenoleukodystrophy. Usually, people with adrenomyeloneuropathy develop symptoms at age 28, but the age of onset may range from 19 to 49 years. Heterozygote women have also been shown to have symptoms of adrenomyeloneuropathy.
Adrenomyeloneuropathy consists of two different forms that vary in severity. They are:
-
Adrenomyeloneuropathy Affecting the Spinal Cord - The milder form of this condition affects only the spinal cord without cerebral involvement.
-
Adrenomyeloneuropathy Affecting the Brain and Spinal Cord - The more severe form of AMN will have a cerebral involvement affecting both the brain and the spinal cord.
The clinical manifestations of adrenomyeloneuropathy vary and might include:
-
Difficulty walking.
-
Weakness.
-
Sphincter dysfunction.
-
Problems with bladder control.
-
Changes in style of walking.
-
Progressive stiffness of the legs.
-
Hypertonia (increased muscle tone).
-
Impaired vibration sense.
-
Impotence.
-
Progressive spastic paraparesis in distal lower extremities with hyperreflexia.
-
Speech difficulties.
-
Nausea.
-
Ataxia (lack of muscle control).
-
Adrenal insufficiency.
-
Sexual dysfunction.
-
Mild peripheral neuropathy.
In addition to the above clinical features, people with the more severe form of adrenomyeloneuropathy will have a cerebral involvement and may develop:
-
Vision loss.
-
Behavioral abnormalities.
Besides the symptoms that people have with this disease, they may have:
-
Abnormality of the cerebral white matter.
-
Alopecia.
-
Blindness.
-
Attention deficit hyperactivity disorder.
-
Bowel incontinence.
These clinical features may vary from person to person, and people with the same disease will not experience all the symptoms listed.
How Is Adrenomyeloneuropathy Diagnosed?
Adrenomyeloneuropathy is usually diagnosed by the presence of specific signs and symptoms. The doctor might undergo a complete physical examination and ask for the symptoms, history of certain diseases, medications (present and past), and family history of the disease. The doctor would suggest a blood test to measure the level of specific body fat known as very long-chain fatty acids. In order to confirm the diagnosis, genetic testing is done for a mutation in the ABCD1 gene. After confirming the diagnosis, an MRI of the brain would be advised to determine if the person has adrenomyeloneuropathy with cerebral involvement (affecting both brain and spinal cord) or without cerebral involvement (affecting only the spinal cord). In addition, the genetic testing registry (GTR) provides valuable information about the genetic tests under this condition where health care professionals and researchers are its intended audience. With its specific answers, the patients may benefit from the health care provider or a genetics professional.
How Is Adrenomyeloneuropathy Treated?
The treatment of adrenomyeloneuropathy is based on the signs and symptoms, and it varies from one person to another. Medications would be prescribed to relieve symptoms and behavioral management therapy is suggested if cerebral involvement is associated with this condition. In the case of adrenal insufficiency, the patient would be recommended steroid replacement therapy. Physical therapy is advised to help build and maintain muscle strength. In addition, the doctor may recommend other mobility devices such as a wheelchair if needed.
Conclusion:
The prognosis for people with adrenomyeloneuropathy varies depending on the type. Adrenomyeloneuropathy with cerebral involvement will have a worse prognosis than AMN without cerebral involvement. However, most people without cerebral involvement can live a happy and successful life with the help of physical therapy, counseling, and management of bladder control issues. With the help of proper treatments, adrenomyeloneuropathy can be treated, and there is nothing to panic about despite whichever type you have.
