Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 15, 2016

Leukodystrophy, also known as hereditary white matter disorders or inherited leukoencephalopathies is a group of rare degenerative disorders involving the white matter of the brain. These disorders arise from improper formation or destruction of the myelin sheath that surrounds nerve fibers.


Definition & Facts

Leukodystrophies are a group of diseases known as rare diseases; in the United States, this means that they affect less than 200,000 people total. Rare diseases are also often referred to as orphan diseases.

Leukodystrophies affect the white matter of the brain. White matter is the portion of the brain that contains bundles of axons, or myelinated nerve cell projections, whereas grey matter consists of the nerve cell bodies. Specifically, they affect the myelin sheath, which is the cover surrounding axons. 

Symptoms & Complaints

Because leukodystrophy encompasses such a large group of disorders, the symptoms vary quite a bit from case to case. These symptoms can present themselves as early as birth or they may not present themselves until adulthood.

In each specific disorder, different parts of the myelin sheath may be affected. The exact portion of the myelin sheath being harmed by the disorder determines the type of neurological problem that presents itself.

Some types of leukodystrophy cause vision problems and hearing loss. Others affect cognition by causing memory loss and cognitive impairment. More lead to diminished motor skills and difficulties with balance. Behavior changes are also known to arise from certain types of leukodystrophy.

Even the ability to eat can be an issue that arises from these disorders. These disorders are progressive diseases, so the symptoms usually get worse as time goes on. These worsening symptoms can lead to seizures, strokes, and many other complications that arise from neurodegeneration.


Most forms of leukoencephalopathy are genetically inherited and arise from mutations in various genes. These disorders can have autosomal dominant, X-linked recessive, or autosomal recessive inheritance patterns.

X-linked recessive traits are caused by a defect in a gene that is linked to the X chromosome. Because they are recessively passed on, X-linked recessive traits are more likely to affect males. A female requires two copies of the defective gene to be passed down to her to develop the disorder, while a male only needs the one to be affected.

Autosomal dominant and autosomal recessive forms of leukoencephalopathy affect males and females at the same rate. They are linked to defective genes attached to the autosomal chromosomes, which are not linked to the sex of a human.

These gene abnormalities, whether they are sex-linked or not, all lead to problems with the myelin sheath surrounding axons in the white matter of the brain. The myelin sheath either does not develop properly due to the genetic defect, or it degrades or is destroyed.

The progressive nature of these disorders causes more nerves to be affected and at greater amounts as the disorder continues. This increase in neurodegeneration leads to an increase in the number and severity of symptoms caused by these disorders. 

Diagnosis & Tests

Diagnosing a patient with leukodystrophy is a multistep process. Inherited leukoencephalopathies usually occur in children. They are observed through symptom presentation.

A detailed family history is taken from the patient to determine if there are any instances of inherited leukoencephalopathy in the family. Both physical examinations and neurological examinations are performed to further assess sensory neuron and motor responses.

To help come to a conclusive diagnosis, magnetic resonance imaging (MRI)s are taken. To come to the diagnosis of leukodystrophy, certain findings are essential in an MRI. For instance, T2 hyperintensity must be noted in the white matter of the patient.

To diagnosis a patient with a specific type of leukodystrophy, molecular genetic testing is usually performed. This helps identify the specific genetic mutation, which correlates with a specific type of inherited leukoencephalopathy. Other tests, such as clinical urine tests further indicate specific types of leukodystrophy.

Treatment & Therapy

Treatment for leukodystrophy is purely dependent on the specific disorder. In addition, in most forms of this disorder, primary forms of treatment are not yet available. Symptom management is the aim of treatment, which involves a multidisciplinary approach, to treat the varying symptoms that present themselves.

Spasticity, where certain muscles are contracted on a continual basis, is usually treated through the use of certain drugs that help manage muscle tone and block signals from neurons that cause the muscles to contract. Some forms of leukodystrophy cause seizures, which are treated with anticonvulsants. These treatments are usually effective, unless the patient is nearing the end of life.

Intellectual disabilities and physical disabilities can be addressed through the use of specialized therapy, such as special education, speech therapy, physical therapy, and occupational therapy. In all cases, routine monitoring and examinations are required to evaluate the progression of the disorder and stop potential problems before they begin.

Prevention & Prophylaxis

For most forms of leukodystrophy, prevention is not an option. However, a few forms of the disorder are possible to prevent through the use of bone marrow transplantation and hematopoietic stem cell transplantation. In Krabbe disease, metachromatic leukodystrophy, and X-linked adrenoleukodystrophy, these procedures seem very beneficial if administered early in the onset of the disease.

For other forms of the disorder, genetic counseling is the only answer for disease prevention. In these instances, the possibilities of passing on the genetic mutation to a child is assessed, so it can be determined if a couple wants to try for pregnancy given the risk of passing the disease onto the child. In addition, prenatal diagnosis and preimplantation genetic diagnosis are possible methods used to help with prevention.