Description

Mld is a rare hereditary (genetic) disorder that causes fatty substances (lipids) accumulate in the cells, particularly in the brain, spinal cord, and peripheral nerves. This accumulation is caused by a deficiency of an enzyme that helps to break down the lipids called sulfatides. The brain and the nervous system gradually loses its function because the substance that covers and protects nerve cells (myelin) is damaged.

There are three forms of mld, which involve different age ranges: late infantile, juvenile and adult. The signs and symptoms can vary. The infantile form is the most common and progresses more rapidly than other forms.

There is No cure for mld yet. Depending on the shape and age of onset, the early identification and treatment can help control some of the signs and symptoms and slow the progression of the disease.

Symptoms

Damage to the protective myelin that covers the nerves results in the progressive worsening of the brain and nervous system functions, including:

  • The loss of the ability to detect sensations such as touch, pain, heat, and sound
  • The loss of intellectual property, thinking and memory skills
  • The loss of motor skills, such as walking, moving, speaking, and swallowing
  • Stiff, rigid muscles, poor muscle function and paralysis
  • The loss of bladder and bowel function
  • Gallbladder problems
  • Blindness
  • Hearing loss
  • Seizures
  • Emotional and behavioral problems, including unstable emotions and the misuse of substances

Each type of leukodystrophy metachromatic occurs at a different age and you can have different initial signs and symptoms and rates of progression:

  • In the late infantile form. This is the most common form of mld, starting at around 2 years of age or younger. The progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood.
  • Juvenile form. This is the second most common form, and it begins in children between the ages of 3 and 16 years of age. The first signs in the behavior and cognitive problems and the increasing difficulty in school. The loss of the ability to walk may occur. Although the youth did not move as fast as the last child, the survival is usually less than 20 years after symptoms begin.
  • Adult form. This form is less common and usually starts after the age of 16 years. Signs of slow progress and can start with the behavior, and psychiatric problems, drug and alcohol abuse and the problems with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stability of symptoms and periods of rapid decline in performance. Adults can survive for several decades after the initial symptoms.

When to see a doctor

Talk with your doctor if you observe any signs mentioned above, or if you have any concerns about your own signs or symptoms.

Causes

Mld is a hereditary disorder caused by an abnormal (mutated) gene. The condition is inherited in an autosomal recessive pattern. The anomaly in the recessive gene is located on one of the nonsex chromosomes (autosomes). To inherit an autosomal recessive disorder, both parents must be carriers, but often do not show signs of the disease. The child inherits two copies of the abnormal gene — one from each parent.

The most common cause of mld is a mutation in the ARSA gene. This mutation results in a lack of the enzyme that breaks down lipids called sulfatides that accumulate in myelin.

Rarely, mld is caused by a deficiency of another type of protein (activator protein) that breaks down sulfatides. This is caused by a mutation in the PSAP gene.

The accumulation of sulfatides is toxic, the destruction of the myelin-producing cells — also called white matter — that protect the nerves. This results in damage to the function of nerve cells in the brain, spinal cord, and peripheral nerves.

Diagnosis

Your doctor will perform a physical exam, including a neurological examination and review of symptoms and medical history to check if there are signs of mld.

Your doctor may order tests to diagnose the disorder. These tests also help determine the severity of the disorder.

  • The laboratory tests. Blood tests to look for an enzyme deficiency that causes the mld. Urine tests can be done to check sulfatide levels.
  • The genetic testing. Your doctor may do genetic testing for mutations in the gene associated with mld. He or she may also recommend tests of family members, especially women who are pregnant (prenatal testing), by mutations in the gene.
  • The nerve conduction study. This test measures electrical nerve impulses and the function of muscles and nerves by passing a small current through electrodes on the skin. Your doctor can use this test to detect damage to the nerves (peripheral neuropathy), which is common in people with mld.
  • Magnetic resonance imaging (MRI). This test uses powerful magnets and radio waves to produce detailed images of the brain. These can be identified with a distinctive striped pattern (tigroid) abnormal white matter (leukodystrophy) in the brain.
  • Psychological and cognitive tests. Your doctor can assess the psychological and the thinking (cognitive) skills, and evaluate the behavior. These tests can help determine how the disease affects the brain function. Psychiatric and behavior problems may be the first signs in juvenile and adult forms of mld.

Treatment

Mld can't be cured, but the clinical trials hold some promise for the future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disease, prevent complications and provide supportive care. Early recognition and intervention can improve outcomes for some people with the disorder.

As the disorder progresses, the level of care required to meet the daily needs increases. Your health care team will work with you to help manage the signs and symptoms and try to improve the quality of life. Talk with your doctor about the possibility of participating in a clinical trial.

Mld can be managed with various treatment methods:

  • Drugs. Medications can reduce the signs and symptoms, such as behavioral problems, seizures, trouble sleeping, gastrointestinal problems, infection, and pain.
  • Physical, occupational, and speech therapy. The physical therapy to promote muscle and joint flexibility and keep the range of movement can be helpful. Occupational and speech therapy may help to maintain the operation.
  • Nutritional assistance. Working with a nutrition specialist (dietitian) can help you to provide proper nutrition. Eventually, it can become difficult to swallow food or liquids. This may require the assistance of the power of the devices as the condition progresses.
  • Other treatments. Other treatments may be needed as the condition progresses. Examples include a wheelchair, walker or other assistive devices; mechanical ventilation to assist with breathing; treatments to prevent or treat complications; and long-term care or hospitalization.

Care of mld can be complex and change with time. Regular follow-up appointments with a team of medical professionals with expertise in the management of this disorder can help prevent some complications and link, with the right support in the home, school, or work.

Potential future treatments

Potential treatments for mld that are being studied include:

  • Gene therapy and other types of cell therapy that introduce healthy genes to replace those who are sick
  • Replacement of the enzyme or to the improvement of the therapy to decrease the buildup of fatty substances
  • Substrate reduction therapy, which reduces the production of fatty substances

Coping and support

The care of a child or family member with a chronic and progressive disease that worsens the disorder as mld can be stressful and tiring. The level of daily physical care increases as the disease progresses. You may not know what to expect, and you may worry about your ability to provide the necessary care.

Please keep in mind these steps to prepare yourself:

  • Learn about the disorder. Learn all you can about mld. Then you can make the best decisions and to be an advocate for you or your child.
  • To find a team of trusted professionals. You will have to make important decisions about care. Medical centers with the expertise of the teams can offer information on the disorder, to coordinate your care among specialists, help you evaluate options and provide treatment.
  • Search for other families. Talking with people who are dealing with similar issues can provide information and emotional support. Ask your doctor about support groups in your community. If a group is not for you, maybe your doctor can put you in contact with a family who has dealt with the disorder. Or you may be able to find individual or support group online.
  • Consider the possibility of support for caregivers. Ask for or accept help in the care of your loved one when needed. Additional options of support could include the question about the sources of respite care, asking for the support of family and friends, and take the time for their own interests and activities. Counseling with a mental health professional can help with the adaptation and coping.
Symptoms and treatment of mld