Adrenoleukodystrophy is the name given to a rare inherited metabolic disorder. It causes various neurological symptoms.
What is adrenoleukodystrophy?
Adrenoleukodystrophy (ALD) also goes by the medical name Addison-Schilder syndrome. It manifests in childhood and is classified as a hereditary disease. Adrenoleukodystrophy (ALD) is also known as Addison-Schilder syndrome. It appears in childhood and is classified as a hereditary disease. It is characterized by a rapidly progressing neurological deterioration, the final phase of which leads to dementia and loss of vital bodily functions. The disease, which is often fatal, almost always manifests itself only in the male sex. Females, on the other hand, usually only transmit the x-linked recessive disease. Only in rare cases is there a defect in both female X chromosomes that results in the onset of adrenoleukodystrophy. In the male sex, the incidence of ALD is 1: 20,000 to 1: 50,000.
Causes
Due to a genetic defect, certain fatty acids cannot be broken down in the body. As a result, both the brain and the spinal cord are affected. Damage also occurs to the adrenal glands because of this. Genetic studies have shown that all patients had mutations within an ABC transporter gene. This gene is located on the X chromosome, gene locus q28. Its function is to encode a protein located in the membrane of peroxisomes. However, its direct involvement in the transmission of superlong-chain fatty acids toward peroxisomes is controversial among physicians. Normally, the degradation of fats takes place inside the peroxisome. In adrenoleukodystrophy, however, the fatty acids accumulate in the white matter of the brain as well as in the adrenal cortex. The overlong-chain fatty acids also accumulate in the cell membranes. Some researchers therefore believe that the membrane structure of the myelin changes in ALD patients, which explains the demyelination. In this way, impulses are prevented from being transmitted, which ultimately manifests itself in the motor and mental decline of affected individuals.
Symptoms, complaints, and signs
Whether adrenoleukodystrophy causes symptoms depends on the sex of the affected person. For example, the altered gene is always located on the X chromosome, which is present only once in males. For this reason, the condition manifests itself almost exclusively in male patients. Since women have two X chromosomes, but the defective gene is usually located on only one of them, they often do not even notice that they have a hereditary disease. However, their male descendants have a 50 percent risk of developing adrenoleukodystrophy. Symptoms almost always occur only in male patients. Impairments in women, on the other hand, show up only rarely and in later years of life. In male patients, the adrenal glands no longer produce sufficient hormones. Therefore, they suffer from low blood pressure, weight loss, weakness and vomiting. In addition, a brownish discoloration of the skin is seen. In some patients, apart from the weakness of the adrenal glands, there are no other symptoms for years. Doctors distinguish between two forms of adrenoleukodystrophy. These are adrenomyeloneuropathy (AMN) and ALD with brain involvement. AMN is considered a milder form of ALD and is seen in almost all adult males who have inherited ALD. Typical signs include coordination difficulties, muscle weakness leading to gait problems, and leg pain. Later on, loss of urine and stool, erectile dysfunction and paralysis are possible. Many patients require a wheelchair as the disease progresses. ALD with brain involvement occurs in one in three boys between the ages of three and twelve. In this case, a severe inflammation of the brain is seen, which progresses further. The affected children, who previously developed normally, suddenly exhibit behavioral changes such as restlessness and poor concentration. Eventually, swallowing disorders, paralysis, deafness and blindness set in. Not infrequently, the disease ends in death.
Diagnosis and course
Diagnosis of adrenoleukodystrophy is considered difficult because the symptoms may be caused by other conditions. Sometimes it takes several years before the correct diagnosis is made. The safest method is a blood test to determine the altered hereditary characteristics. In addition, imaging procedures such as magnetic resonance imaging (MRI) of the skull can be performed, which helps the physician identify demyelinated and atrophic brain areas. The prognosis of adrenoleukodystrophy depends on the particular form of progression. For example, life expectancy is considered normal in AMN, whereas severe disability and need for long-term care are present after two to four years in brain involvement.
Complications
As a genetic metabolic disease that fails to break down vital fatty acids in the body, adrenoleukodystrophy causes severe neurologic damage. In some cases, the disease breaks out in infancy. The mental and sensorimotor development shows considerable deficits. The life expectancy of affected children is between 10 and 14 years. Adrenoleukodystrophy is located on the X chromosome. Males are therefore more at risk than females. When the symptoms appear in adults is unpredictable. Women, on the other hand, do not belong to the risk group until late in life. Those who are prone to adrenoleukodystrophy due to familial predispositions in their genetic makeup should be advised if they show signs such as: Disease of the adrenal glands, fatigue, weight loss, nausea, brownish skin discoloration, seek medical help immediately. Otherwise, there will inevitably be drastic complications, which will negatively affect the quality of life as well as life expectancy. The final stage can be accompanied by bed confinement, total degeneration of the nervous system and organ failure. Sometimes this leads to death. Once a diagnosis of adrenoleukodystrophy is made, symptoms can be alleviated but not cured. Therapy and medication are tailored to the individual affected, as the disease has different specifications. Medication alleviates spastic muscle spasms and can make the accompanying neurological symptoms and inflammatory processes in the brain more tolerable. Nutritionally, Lorenzo’s oil is administered to lower elevated fatty acid levels. Depending on the patient’s condition, bone marrow transplantation may be performed.
When should you see a doctor?
As a rule, adrenoleukodystrophy does not cause particular and specific complaints or symptoms that could directly indicate the disease. For this reason, an examination by a physician is necessary in any case to avoid possible consequential damage that could occur if the disease is detected late. If the affected person suffers from weight loss and low blood pressure, a doctor must be consulted. Not infrequently, loss of consciousness may also occur. As a rule, the general practitioner can be consulted first, who will refer the patient to a specialist if a diagnosis is made. An urgent visit to the doctor is advisable if coordination disorders or gait disturbances continue to occur. Similarly, hearing complaints may indicate adrenoleukodystrophy. If adrenoleukodystrophy is more advanced, paralysis or loss of urine may also occur. When these symptoms occur, urgent treatment of the patient is necessary. It is not uncommon for sudden visual complaints or, in the worst case, complete blindness to occur in addition to deafness.
Treatment and therapy
A cure for adrenoleukodystrophy is not possible. Therefore, therapy is limited to alleviating the symptoms. Thus, adrenal gland failure is readily treatable by administration of the missing hormones. Furthermore, the patient is given drugs against spastic muscle spasms. Some patients also receive so-called Lorenzo’s oil. This is a mixture of glycerol trierucate and glycerol trioleate. The ratio is 4:1, and the administration is intended to lower the concentration of superlong-chain fatty acids to a more favorable level. In addition, physiotherapeutic exercises or occupational therapy can be performed to help loosen the muscles. In the case of dysphagia, artificial feeding is feasible. Psychotherapeutic care can also be useful.
Outlook and prognosis
Adrenoleukodystrophy generally makes the affected person feel sick and weak, and the patient’s ability to cope with stress is also significantly reduced by the disease. Low blood pressure occurs, resulting in pallor of the face. Furthermore, the low blood pressure may also cause a loss of consciousness. The affected person often loses weight and also suffers from diarrhea and vomiting. The skin may turn brownish. Pain also occurs in the muscles and legs. Coordination decreases and gait disturbances often occur, so that the affected person limps or walks with a limp, for example. The quality of life is considerably limited and reduced by the symptoms of adrenoleukodystrophy. In the course of the disease, patients are often dependent on the help of other people or on the use of a wheelchair. Concentration also decreases and inner restlessness occurs. Without treatment, the patient will die. The treatment itself can be carried out by administering the missing hormones, and there are no particular complications.
Prevention
If adrenoleukodystrophy is known to occur in a family, screening of all male relatives is recommended. In this way, early treatment can be given if necessary.
Follow-up
In general, the options for follow-up care in adrenoleukodystrophy are relatively limited. Affected individuals rely on ongoing treatment for this disorder to relieve symptoms and prevent further complications. In this context, early diagnosis and treatment have a very positive effect on the further course of the disease. In most cases, adrenoleukodystrophy is treated by taking the hormones that the affected person lacks. In this case, the patient must pay attention to regular intake of the medication, and possible interactions with other medications should also be taken into account. In the case of children, the parents must pay attention to the regular intake of the medication so that there are no disturbances or complications. Furthermore, most patients rely on physical therapy to relieve discomfort in the muscles. Many of the exercises from this therapy can also be performed at home to increase the mobility of the affected person. The patient’s life expectancy is not negatively affected by this condition. Since in some cases adrenoleukodystrophy can also cause psychological discomfort or depression, conversations with friends or with one’s own family are very useful in this regard.
This is what you can do yourself
Adrenoleukodystrophy (ALD) is a hereditary metabolic disease that affects men significantly more than women. There are no self-help measures that are suitable for treating the disease causally. However, those affected can help manage the risks and mitigate the severity of the disease’s progression. Although many symptoms of the disease can be treated well, those affected often do not receive adequate treatment until far too late because the disease, which is very rare, has not been properly diagnosed. If ALD has already occurred in a family, patients should point this out to a physician and insist that a specialist be consulted to clarify the suspicion of ALD. Women who are carriers of the defective gene need to be aware that while they themselves will either not develop the disease or will develop only mild symptoms, the likelihood that their male offspring will suffer from a severe form of ALD is very high. This should be taken into account in family planning. For carriers of hereditary diseases, there are counseling centers to assist them with family planning issues. Affected persons who already have the disease should pay attention to a low-fat diet in order to keep the concentration of harmful fatty acids in the blood low. If muscles or motor functions are affected, physiotherapy should be started as early as possible to counteract degenerative development.
