Leukodystrophy: Types, Symptoms, Causes & Treatment


Leukodystrophy is not a single disease or condition, but a group of diseases that affect the white (leuko) matter of the brain and often the spinal cord. The condition is caused by the inexact development of the myelin sheath that acts as the insulator for the nerve fibres. And, it causes the degeneration of the white  matter. The damage or the degeneration of the white matter causes inflammation to the central nervous system (CNS), as well as the loss of myelin. The communication between the nervous system and the brain is disrupted and gradually becomes non-existent.

Leukodystrophy can result in diminished vision and hearing and decreased motor functions. Although the disease is fatal, age and type of condition are critical factors in determining the life expectancy of the diagnosed. In the case of infants, the lifespan between 2 to 8 years is given, while adults have a longer chance of living (more than a decade). The lack of treatment and a cure for the condition has caused the disease to be the centre of extensive researches.

Mostly progressive, leukodystrophies worsen over time with the nerve tissues failing to operate normally. Leukodystrophies are  predominantly genetic, that is, they are passed down from the parent to the child.

There are over 50 different types of the condition, with new ones being classified every year. According to the recent reports, there are almost  30 different types of leukodystrophies. In addition to that, there are many more types of the condition and many more left to be recognised and classified. Some of the most common types of leukodystrophies include

One of the common types of leukodystrophies, ALD affects the male gender (X-linked gene) typically. It is found in boys, with the  symptoms arising before the age of 10 years. ALD progresses rapidly and can affect the adrenal glands too, causing the limited and restricted production of cortisone. In the case of adults, this genetic shift can lead to  adrenomyeloneuropathy, affecting the adrenal glands and spinal cord.

This type of leukodystrophy causes abnormal growth of myelin. The spongy degeneration results in abated tone, regression, enlarged head and limited  head control. The condition worsens over time, resulting in stiffness. Life expectancy is limited for Canavan's disease.

Another commonly found type of leukodystrophy, this condition has a wide range of subtypes. Most of the subtypes of MLD are age-related, such as late  infantile MLD, juvenile MLD and adult MLD etc. In the case of infantile MLD, the first signs will be the  loss of motor (movement) and verbal skills.

Affecting the myelin of the peripheral and central  nervous systems, this type of leukodystrophy is commonly found in babies. 90% of the reported cases of Krabbe disease are found in babies, with the signs and symptoms arising before the baby is six months old. Rare cases of Krabbe disease in adults  have also been reported.

Also termed as the childhood ataxia with cerebral hypomyelination (CACH), this type of leukodystrophy is caused during the first  five years of life. VWMD affects the speech and motor skills, causing a progressive deterioration. Resulting in the mildly delayed development and growth, VWMD is also found in adults in some rare cases.

The signs of the condition can appear shortly after birth and in some cases, the individuals develop it during childhood or adulthood. In accordance with the type of the leukodystrophy and the extent of the white matter damage, the signs and  symptoms may vary. However, the one common symptom in all cases of the condition is the abnormal development of the brain's myelin sheath. Some of the most common symptoms include

As the condition progresses, the symptoms  can include

Generated by particular gene abnormalities, the genetic disorders are  inherited. That is, it is passed down through the genes. Each and every type of leukodystrophy has a certain pattern of inheritance accorded to it.

It occurs in the event of an individual inheriting two copies of the abnormal gene, one from each parent. In this case, the child will only inherit the condition if both the parents are carrying the gene. Autosomal recessive affects both boys and girls. It will  not reflect any symptoms on the carrier parents, but, there is a one in four chance that the child will develop leukodystrophy or even become the carrier of the genes. A person becomes a carrier when he/she receives one disease gene and one normal gene.

It occurs when a single abnormal gene causes the disorder. The abnormal gene could be inherited from either of the parents or can occur due to the any  new mutation or gene change in the individual who is affected. During pregnancy, there is a 50% chance of the affected gene being inherited to the child, with the risk being the same for males and females.

In this case, the gene will be carried on by the X chromosome that determines the sex of the baby. Women have two X chromosomes, whereas men have an  X chromosome and a Y chromosome. So, when there is a genetic change, men are affected as they have no additional X chromosome to compensate. Also, girls and boys are affected differently.

The white matter of the brain can be affected due to other reasons and conditions such as an infection, ischaemia, other metabolic conditions and multiple sclerosis.

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Consequently, due to the lack of information and limited understanding, there has been a void in understanding the genetic disorder condition. Therefore, the diagnosis of leukodystrophy is not very easy and is often difficult. The diagnosis  of the disorder is will be in need of drawing in the input of various specialists including geneticists, neurologists, and metabolic physicians. Depending on the type of the genetic disorder, the methods will include

In this diagnosis method, magnetic field and pulses of the radio wave energy will be used to create a detailed image of the affected areas (brain, spinal cord etc.). The images will help identify the abnormalities and help the process of diagnosis. MRI exam is  advised more as it does not expose the child to radiation as an x-ray or CT scans.

Under this method, the DNA of the individual will be analysed in order to assess any changes in the genes, that could be causing the leukodystrophy.

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Here, various tests will be conducted to examine and analyse the cognitive function. This method will help the medical  professional in understanding the ways through which the condition is affecting the individual's concentration and reasoning abilities etc.

The other diagnosis methods include

As of now, researchers and their findings have revealed that there is no significant cure for the genetic disorder. Studies have  revealed that bone marrow transplantation and stem cell therapy have been useful in some cases. Bone marrow transplant, in some cases, has slowed down the progression of the disease.

Time, the severity of the symptoms and age of onset are critical factors that determine the treatment benefit on the diagnosed individual. Therapies have been  said to have a positive impact and gene therapy and enzyme replacement therapy are being researched currently to properly analyse and understand its effective role in the treatment for leukodystrophy.

The most common and effective  treatment methods include

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