Menkes syndrome is an X-chromosomal recessive disorder of copper metabolism in which the intestine does not adequately absorb the trace element. The undersupply of copper manifests in the muscles, nervous system, and skeleton. The disease is as yet incurable and prognostically unfavorable.
What is Menkes syndrome?
Menkes syndrome is also known as Menkes disease. This disease corresponds to a hereditarymetabolic disorder. The disease primarily involves a disorder of copper metabolism. Copper is the third most abundant trace element in the human body. The skeleton and muscles as well as the brain and liver contain copper. In addition, the substance is involved in the formation of connective tissue. As a component of enzymes such as superoxide dismutase, the trace element also protects the body from free radicals and oxidative stress. Apart from these functions, copper also plays a role in energy production. Accordingly, copper deficiency has a negative effect on the body. Chronic copper deficiency is present in Menkes disease. The syndrome is named after its first describer, J. H. Menkes, who documented the disease in the 20th century. Other disorders with copper deficiency as a leading symptom include those such as Wilson’s disease, which is associated with comparable symptoms. With a prevalence of one in 100,000, Menkes disease is slightly less common than Wilson disease.
Causes
The cause of Menkes disease is a genetic defect caused by a mutation in the ATP7A gene. The ATP7A gene does the coding for an intracellular protein for copper transport. In the case of normal copper absorption, the mutation thus leads to impaired copper release. The absorption of copper in the intestine is impaired and the trace element is incorrectly distributed. Decreased concentrations are present in the liver and brain, while concentrations are increased in the intestinal cells, heart, pancreas and kidneys. Menkes disease is genetically present at site X 13.3 and therefore affects only boys. Girls can carry the defect without having problems. Unlike boys, they are endowed with a second X chromosome. The gene product of the second, healthy chromosome can therefore cancel out the impairments of the first. Inheritance of Menkes syndrome is X-chromosomal recessive.
Symptoms, complaints, and signs
During the first eight to 10 weeks of life, infants with Menkes syndrome are usually asymptomatic. Severe muscle weakness does not set in until about two months of age. Feeding problems and developmental problems occur. The copper deficiency in the brain can manifest itself in epileptic seizures and restricted movement. Scaly rashes often appear on the patients’ less elastic skin. The hair, eyelashes and eyebrows become crooked, brittle and take on a white to silver-gray color. The face usually appears expressionless and sunken. In addition, skeletal changes such as a funnel chest may occur. Inguinal hernias and umbilical hernias often accompany the clinical picture. Depending on the course, severe bone fractures and vascular changes may already occur at this time.
Diagnosis and course of the disease
If Menkes disease is suspected, the physician takes a urine and plasma sample. The laboratory checks the plasma for the copper storage protein caeruloplasmin. The general copper level is also determined in both samples. X-rays confirm the suspicion of Menkes disease with vertebral anomalies and switching bones. Cell deaths in the thalamus or cerebellum can also confirm the suspicion. If necessary, these phenomena can be observed by MRI. A molecular genetic examination of the ATP7A gene can provide conclusive evidence of a mutation. The prognosis for patients with Menkes syndrome is generally unfavorable. Most affected individuals do not reach adulthood. In particularly severe cases, patients die in infancy. The type and localization of the gene mutation has the greatest impact on prognosis. Early detection of the disease can have a positive prognostic effect.
Complications
In many cases, the first symptoms of Menkes syndrome do not appear until several months after birth, so direct and early treatment of this complaint is not possible. In this case, the patients primarily suffer from a severely pronounced muscle weakness and thus from a reduced ability to bear weight.Especially in children, this muscle weakness can lead to significant restrictions in development and thus also significantly reduce the patient’s quality of life. Furthermore, it is not uncommon for epileptic seizures to occur, which can lead to severe pain. The skin of the affected person is usually reddened and scaly. Also, the muscles in the face can hardly be moved, so that the affected persons often appear apathetic and listless. Not infrequently, parents are also affected by Menkes syndrome and suffer from psychological complaints or depression. Unfortunately, a direct and causal treatment of the syndrome is not possible, so that the treatment only aims at limiting the various complaints. However, this does not lead to further complications. The affected persons are dependent on medication. Likewise, various therapies can alleviate the symptoms. As a rule, Menkes syndrome does not reduce the patient’s life expectancy.
When should you see a doctor?
If irregularities occur in a newborn child during the second or third month of life, a visit to the doctor should be made. Menkes syndrome is characterized by severe muscle weakness, and there are also problems with feeding. The symptoms are not present in the first few days after birth, but become apparent within the first eight weeks of life. If parents notice a decrease in muscle strength in their offspring, a doctor should be consulted as soon as possible. Restrictions in mobility or abnormalities in movement patterns are further signs of a present disorder. They should be immediately evaluated by a pediatrician. If the child suffers from epileptic seizures, the greatest care should be taken. A physician should be consulted after any seizure disorder so that a comprehensive medical examination can be performed. If there are growth disturbances or irregularities in the child’s development, a physician should be consulted. Frequent bone fractures or changes in the skeletal system indicate inconsistencies and should be investigated. Abnormalities of the skin appearance, scaling of the skin or peculiarities of the hair, eyebrows as well as eyelashes should be presented to a doctor. Since the disease has a poor prognosis, a visit to the doctor is recommended as soon as possible in case of changes. The sooner symptoms are treated, the more optimal medical professionals can make the child’s quality of life within the given possibilities.
Treatment and therapy
Menkes syndrome is incurable. Only symptomatic therapies are available to date. The disease prevents the absorption of copper in the intestine. Therefore, nothing can be directed therapeutically via oral copper administration. Instead, copper must be given parenterally, because in this way the substance does not have to pass through the gastrointestinal tract. Copper histidinate is usually administered. This substance has proven to be the most tolerable and at the same time the most effective form of therapy. Copper histidinate is injected into the subcutaneous fatty tissue. As a copper transport protein, it is thus present in the blood and penetrates the blood-brain barrier to reach the brain. Ideally, treatment begins before the nervous system is affected by damage. If therapy is not started until later, the substance can usually no longer delay the progressive course of the disease. The neurological development of those affected is positively influenced by the early administration of copper histidinate in most cases. However, the manifestation of the disease in the connective tissue cannot be influenced by this form of therapy. A causal therapy is not yet available. In the future, medicine may develop an original treatment by replacing the mutated gene. In animal experiments, cure has already been achieved by ATP7A gene addition.
Prospect and prognosis
Menkes syndrome has an unfavorable prognosis. The patient suffers from a hereditary metabolic disorder. Since changes in genetics are not possible, physicians can only treat the symptoms that occur as best they can. Characteristic of the disease are developmental disorders and a seizure disorder. In the first months of life, there are usually no health impairments. This leads to the fact that the hereditary disease appears and can be diagnosed only after some years. Medication is administered because the absorption of copper in the intestine is prevented.Without medical care, severe health impairments can be expected. Muscle weakness, pain, reduced quality of life and numerous secondary disorders occur. To alleviate the symptoms, the affected person is dependent on medication for the rest of his or her life. As soon as the prescribed drugs are discontinued, regressions of the irregularities must be documented immediately. The prognosis is significantly worse if the nervous system is already affected by damage. This is especially true if the diagnosis is made at an advanced stage. In these cases, neurological development can no longer be influenced. If the diagnosis is made at an early stage, the course of the disease can be positively supported to a considerable extent. Nevertheless, there is currently no treatment option to adequately treat the disease at the connective tissue.
Prevention
Because Menkes syndrome corresponds to a hereditary gene mutation, the disease cannot be prevented to date. The risk for a diseased child may be assessed during child planning by molecular genetic sequence analysis.
Follow-up
Because treatment of Menkes syndrome is relatively complex and lengthy, follow-up care focuses on managing the disease with confidence. Affected individuals should try to maintain a positive attitude despite the adversity. To build this, relaxation exercises and meditation can help calm and focus the mind. Menkes syndrome is associated with various serious complications and discomforts, all of which can have a very negative impact on the quality of life and also on the daily life of the affected person. Therefore, a doctor should be contacted at the first signs and symptoms of the disease to avoid further worsening of the symptoms. The persistent muscle weakness and disturbances in the child’s development can lead to bullying or to teasing in everyday life. If psychological upsets become apparent that last longer, a psychologist should be consulted to clarify this. Sometimes therapy can help to better accept the disease and the treatment process.
What you can do yourself
There is no cure for Menkes syndrome so far. Therapy focuses on treating the symptoms and discomfort. Parents who notice developmental problems and symptoms of muscle weakness in their child should first talk to a doctor. In consultation with the physician, an individual therapy can then be started. The first step is to alleviate the symptoms through orthopedic and physiotherapeutic measures. The affected children need a lot of support and affection, especially in the first years of life. In addition, care should be taken to ensure that the sufferer gets plenty of exercise and eats a healthy diet. Although this does not alleviate the symptoms, it does improve the child’s well-being and quality of life. This should be accompanied by talking to the child about the disease. In this way, the child learns to understand the symptoms and their effects, and in most cases is better able to cope with them. If the course of the disease is severe, therapeutic support is indicated, since in most cases the affected children die before reaching adulthood. The details of what measures should be taken should be determined in light of the child’s condition and in consultation with the appropriate physician.
