What is Leukodystrophy?

The white matter of the brain is composed of nerve fibres (wires) that form connections between the nerve cells, and the myelin which insulates the nerve fibres. Abnormal changes or damage to the white matter can prevent nerve cells from sending messages to different parts of the body, impacting brain function.

White matter disorders are all disorders where the white matter of the brain is predominately involved. The medical word for this is leukoencephalopathy. White matter disorders comprises many different disorders which all have different consequences for brain function. Therefore, the prognosis for an individual with a white matter disorder is highly variable. Some disorders are progressive and others are not depending on the cause of the white matter disease.


The word Leukodystrophy comes from the Greek roots leuko (white), dys (lack of) and troph (growth). Leukodystrophies are a group of genetic white matter disorders. Although they are individually rare, as a group, these disorders affect around 1 in 5000 individuals. Leukodystrophies can cause problems with movement, speaking, vision, hearing, and overall development. They are progressive, meaning that they tend to worsen throughout the life of the patient. Leukodystrophies can be demyelinating (loss of previously formed myelin) or hypomyelinating (reduced or absent myelin).

Click on the image below to see the different symptoms that can be associated with leukodystrophies.


Clinical symptoms

Clinical history can help us understand the disease progression and family history can help us understand the possible mode of inheritance. Findings from a physical examination, like the presence of other abnormalities, may also provide important diagnostic clues.


Leukodystrophy is usually first detected by imaging such as Magnetic Resonance Imaging (MRI). MRI is still typically the first technique used as it has extreme sensitivity in identifying which white matter structures of the brain are affected.

Laboratory tests

Tests that may be performed include:

  • Urine and plasma amino acids and organic acids
  • Blood and CSF levels of lactate and pyruvate,
  • Lysosomal enzymes in white blood cells
  • Very long-chain fatty acids and phytanic acid,
  • Analysis of mitochondrial DNA, and assessment of mitochondrial function
  • Analysis of hormone levels, especially adrenal hormones,
  • Vitamin levels

It is important to also evaluate the function of other organs, including the ears, eyes and internal organs.

Genomic testing

Genomic testing has both greatly increased the number of known leukodystrophies and improved diagnosis. The percentage of leukodystrophy cases without a specific diagnosis has decreased from about 50% in 2010 to 20-30% in 2016, and this number continues to decrease.


All humans have about 20,000 genes that come in pairs. One copy comes from the mother and the other copy comes from the father. Inherited white matter disorders are caused by a defect in a gene. This leads to dysfunction or abnormal amounts of a protein which can result in abnormal amounts of myelin or loss of myelin. There are different modes of inheritance:

1. Autosomal recessive inheritance

This is the most frequent mode of inheritance where the affected individual has a defect in both copies of the gene. The parents of the affected individual each carry one copy of the gene defect but they typically do not show signs and symptoms of the condition. There is a 25% chance for each pregnancy that the child will receive both defective genes and have the disease.

2. Autosomal dominant inheritance

This means that one gene with a defect is enough to cause a disease. In that case, either the father or the mother has the disease. There is a 50% chance for each pregnancy that the child will have the disease. It is also possible that the child has a new defect not seen in the parents (called de novo). It is also possible that the father or the mother carries a new defect in their germ cells in which case there is a chance of recurrence at following pregnancies, but it is not as high as 50%.

3. Maternal inheritance

This mode of inheritance is seen in “mitochondrial disorders”. Mitochondria are the structures that produce the energy in all cells of the body. They have a small piece of DNA in them with a small set of genes. The sperm cell has no mitochondria, but the ovum has mitochondria. This means that children have received all mitochondria from their mother. Defects in mitochondrial genes may occur de novo in a child or be inherited from their mother, who may or may not be affected by the condition herself. The severity of the disease depends on the proportion of mitochondria that carry the gene mutation. If inherited, there is a chance of recurrence in a future pregnancy for the mother, but the size of this risk is difficult to predict.


Leukodystrophies can present at any age. In general, early onset is associated with more severe symptoms and rapid decline.

Management and treatment

Many interventions are available to manage disease symptoms to improve the quality of life of individuals with white matter disease. Physical therapy and special education are usually needed. Often, more intensive medical treatment is required.

With recent technological advances and natural history data established, curative therapy for leukodystrophies are being developed. For more details see our other research page.