What are Leukodystrophies?

A leukodystrophy is a genetic disorder, or a disorder caused by problems in the genes, resulting in a problem with the white matter of the brain. The white matter of the brain is the central part of the brain that is made of myelin and the glial cells. Myelin is the insulation made by some of glial cells, which helps support the projections of the nerve cells in and out of the brain. Glial cells are a special type of cell in the brain that act to support and enhance the function of the nerve cells. They include oligodendrocytes, astrocytes and microglia.

Most leukodystrophies are caused by one or two abnormal copies of genes critical to the function of the glial cells. These abnormal genes can result in either missing proteins or enzymes that result in injury to the cells or myelin in the brain. As a result, critical functions of the white matter are disrupted. Leukodystrophies can be inherited in many different ways, or sometimes be in only one individual in a family.

There are at least two dozen disorders considered to be leukodystrophies. In addition, some other genetic disorders are classified as genetic leukoencephalopathies and have many things in common with the leukodystrophies. For a complete list of specific disorders, please click here.

Patients with leukodystrophy may have many different symptoms, but some of the symptoms are common across most of the leukodystrophies.  These include symptoms of increased tone in the muscles of the arms and legs. Increased tone may take the form of spasticity and or dystonia. Patients may also have decreased tone in the body, called hypotonia. Patients may also have problems with balance, most often called ataxia.  Together these symptoms may cause problems with using muscles for walking, talking, and fine motor control.

Many patients have preserved cognitive skills, at least in the beginning of the disease.  Over time, depending on the type of leukodystrophy, other medical complications may develop, to include problems with chewing and swallowing, digestion and gastro-esophageal reflux (or heart burn), breathing and sleeping problems. Some, but not all, patients may have seizures.

Some leukodystrophies progress rapidly, with changes in patient health and well-being over the course of month, while other leukodystrophies progress only very slowly if at all, with changes measured in years or even decades. Patients can develop symptoms of a leukodystrophy at any age, from infancy to late adult-hood, but some disorders tend to present more often in certain age groups.

How Common Are Leukodystrophies?

The truth is - it's hard to say. Some estimates put the incidence as high as 1 in 7,000 individuals, while other estimates are far lower - one study suggested that only 1 in 100,000 individuals are affected. By any measure, leukodystrophies are rare diseases.

We are still in the process of uncovering the true burden of these diseases. Many individuals with leukodystrophies go undiagnosed for months or even years. Undocumented cases further complicate the task of estimating the true disease incidence.

Can Leukodystrophies be Treated or Cured?

Leukodystrophies are inborn genetic disorders and cannot be cured. However, many disorders can be treated clinically by a complex care team. In some cases, disease progression can be slowed and symptoms can be managed or eliminated all together.

Research is paving the way for more advanced and effective clinical approaches to disease management. In fact, many of our own GLIA experts have participated in projects that have produced better clinical approaches to disease management, giving new hope to individuals affected by leukodystrophies.