Menkes Disease

Menkes disease, also known as kinky hair syndrome or steely hair disease, is a rare genetic disorder that affects the metabolism of copper in the body. Copper is an essential mineral that is required for the proper functioning of various enzymes, which play a critical role in various physiological processes such as the formation of collagen, the transportation of iron in the blood, and the production of energy.

The disease is caused by mutations in the ATP7A gene, which provides instructions for making a protein that helps transport copper into various tissues and organs. When the ATP7A gene is mutated, the body is unable to produce enough of this protein, leading to a buildup of copper in the liver and a deficiency of copper in the brain and other tissues.

Menkes disease is an X-linked disorder, which means that it is caused by mutations on the X chromosome and primarily affects males. Females are usually carriers of the disease and can pass it on to their children, but they usually do not develop symptoms themselves.


There are several different types of mutations that can occur in the ATP7A gene, including:

  1. Nonsense mutations: These mutations result in the production of a truncated protein that is unable to function properly.
  2. Missense mutations: These mutations result in the production of a protein that has a different amino acid sequence than normal, which can impair its function.
  3. Frameshift mutations: These mutations result in the addition or deletion of one or more nucleotides in the gene, which can change the entire amino acid sequence of the protein.
  4. Splice site mutations: These mutations result in the alteration of the normal splicing of the gene, which can result in the production of a nonfunctional protein.

Menkes disease is an X-linked recessive disorder, which means that the ATP7A gene is located on the X chromosome, and only one copy of the gene is necessary for the disorder to develop. This also means that the disease is more common in males, as they have only one X chromosome, whereas females have two X chromosomes and are usually carriers of the disease.

The severity of Menkes disease varies greatly depending on the type of ATP7A gene mutation that is present. In some cases, the disease is severe and leads to death in early childhood, while in other cases, the disease may be milder and allow for some degree of developmental progress and survival into adolescence or adulthood.


There are several causes of Menkes disease, which can be broadly categorized into genetic and environmental factors.

  1. Genetic Causes: Menkes disease is caused by mutations in the ATP7A gene, which provides instructions for making a protein that is involved in the transport of copper from the liver to other parts of the body. Mutations in this gene result in a decrease in the amount of functional ATP7A protein, leading to an accumulation of copper in the liver and a deficiency of copper in other tissues and organs.

The ATP7A gene mutations that cause Menkes disease are usually inherited in an X-linked dominant pattern, meaning that the gene is located on the X chromosome and that females have two copies of the gene, while males have only one. This results in a higher frequency of the disease in males, who are more likely to inherit the mutated gene from their mother.

  1. Environmental Factors: Environmental factors can also play a role in the development of Menkes disease. Copper is an essential mineral that is obtained from the diet, and a lack of adequate copper in the diet can lead to a deficiency of the mineral in the body. This can be particularly problematic in individuals with Menkes disease, who are unable to absorb and utilize copper effectively, leading to an even greater deficiency of the mineral.

In addition, exposure to certain environmental toxins, such as cadmium and lead, can interfere with the absorption and utilization of copper in the body, exacerbating the symptoms of Menkes disease.


The main symptoms of Menkes disease can be broadly categorized into three main categories: neurological symptoms, skeletal symptoms, and cutaneous symptoms.

Neurological symptoms are the most prominent and debilitating symptoms of Menkes disease. The symptoms typically appear within the first three months of life and can include developmental delays, muscle weakness, and seizures. Infants with Menkes disease may have difficulty with basic motor skills such as holding their head up, crawling, or sitting up. They may also experience muscle wasting, leading to a decreased ability to move and control their limbs. Seizures are a common symptom of Menkes disease and can be difficult to control, even with medication. These seizures can range from mild tremors to severe convulsions and can cause significant distress for both the affected child and their family.

Skeletal symptoms of Menkes disease can also be severe and can include fractures, joint deformities, and scoliosis. Infants with Menkes disease may have bones that are brittle and prone to breaking, even with minimal trauma. Joint deformities, such as clubfoot or dislocated hips, can also occur and may require surgical intervention to correct. Scoliosis, or curvature of the spine, can also develop in children with Menkes disease and can cause pain and difficulty with movement.

Cutaneous symptoms of Menkes disease can include changes in hair texture and color, as well as skin rashes and ulcerations. The hair of affected children may be thin, brittle, and have a distinctive “kinky” appearance. The hair may also change color and become lighter or coarser as the child grows. Skin rashes and ulcerations can also occur and can be painful, especially in areas of the body that are exposed to friction, such as the elbows and knees.

The symptoms of Menkes disease typically begin to develop in the first few months of life and include:

  1. Stunted growth and development: Infants with Menkes disease often have delayed growth and developmental milestones, including delayed crawling, walking, and speech.
  2. Neurological symptoms: Menkes disease can cause a variety of neurological symptoms, including seizures, intellectual disability, and spasticity.
  3. Characteristic hair: Infants with Menkes disease often have sparse, brittle, and kinky hair, which is a hallmark of the disease.
  4. Skin abnormalities: Infants with Menkes disease may have skin abnormalities, including wrinkled skin and a purplish discoloration of the skin.
  5. Gastrointestinal symptoms: Infants with Menkes disease may experience gastrointestinal symptoms, including diarrhea and vomiting.


Diagnosis of Menkes disease typically begins with a thorough physical examination and a review of the patient’s medical history. There are several key diagnostic tests and procedures that can be used to diagnose Menkes disease and determine the severity of the condition.

  1. Clinical examination: A clinical examination is the first step in diagnosing Menkes disease. During the examination, the doctor will look for signs of the characteristic kinky hair and wrinkled skin that are often associated with the disorder. The doctor will also perform a thorough neurological examination to assess the child’s muscle tone, reflexes, and developmental milestones.
  2. Blood tests: Blood tests are used to measure the levels of copper in the blood and to assess the patient’s overall health. A blood test can also be used to determine if the patient has a genetic mutation associated with Menkes disease.
  3. Urinalysis: Urinalysis is a test that measures the levels of copper in the urine. This test can help to determine the severity of the condition and can be used to monitor the patient’s progress over time.
  4. Liver function tests: Liver function tests are used to evaluate the health of the liver and to determine if the liver is functioning properly. Menkes disease can affect the liver, so these tests are important for monitoring the patient’s health.
  5. Electroencephalogram (EEG): An EEG is a test that measures the electrical activity of the brain. This test can be used to assess the patient’s neurological function and to determine if there is any damage to the brain as a result of Menkes disease.
  6. Magnetic resonance imaging (MRI): An MRI is a test that uses magnetic fields and radio waves to create detailed images of the body’s internal structures. This test can be used to evaluate the brain and other organs for signs of damage or disease.
  7. Biopsy: A biopsy is a procedure in which a small sample of tissue is taken from the body and examined under a microscope. A biopsy can be used to confirm the diagnosis of Menkes disease and to determine the severity of the condition.

Once a diagnosis of Menkes disease has been made, the patient’s doctor will work with a team of specialists to develop a treatment plan. This may include medications to manage symptoms, dietary changes to ensure adequate copper intake, and close monitoring of the patient’s health to detect and manage any complications that may arise.


There is currently no cure for Menkes disease, but there are several treatments that can help manage its symptoms and improve quality of life. Here is a list of the main treatments for Menkes disease:

  1. Copper supplementation: The most important aspect of treatment for Menkes disease is to replenish the body’s copper levels. This can be done through intravenous (IV) administration of copper histidine, a form of copper that is well-absorbed by the body. Copper supplementation can help improve the symptoms of Menkes disease, but the optimal dose and frequency of treatment are still under investigation.
  2. Physical therapy: Physical therapy can help improve mobility and coordination in individuals with Menkes disease. This can include exercises to improve strength and range of motion, as well as activities to improve balance and coordination.
  3. Occupational therapy: Occupational therapy can help individuals with Menkes disease develop fine motor skills and improve their ability to perform daily activities. This may include activities such as playing with toys, using utensils, and manipulating objects.
  4. Speech therapy: Speech therapy can help improve communication skills in individuals with Menkes disease. This may include exercises to improve speech, language, and oral motor function.
  5. Nutritional support: Proper nutrition is important for individuals with Menkes disease, as malnutrition can exacerbate the symptoms of the disorder. A balanced diet that is rich in vitamins and minerals, especially copper, can help support growth and development.
  6. Anticonvulsant therapy: Seizures are a common complication of Menkes disease, and anticonvulsant therapy can help control them. The choice of anticonvulsant medication will depend on the frequency and severity of seizures, as well as any other medical conditions the individual may have.
  7. Respiratory support: Individuals with Menkes disease may require respiratory support, such as a ventilator, as the disease progresses and the nervous system deteriorates. Respiratory support can help improve breathing and prevent respiratory failure.
  8. Palliative care: Palliative care is an approach to medical care that focuses on improving quality of life and reducing suffering for individuals with serious illnesses. This may include measures such as pain management, emotional support, and end-of-life care.

It is important to note that each individual with Menkes disease will have unique needs and treatment plans, and that treatment should be tailored to meet their specific needs and goals. The best way to manage Menkes disease is through a multidisciplinary approach that involves a team of healthcare professionals, including a pediatrician, neurologist, genetic counselor, physical therapist, occupational therapist, speech therapist, and dietitian.