Leukodystrophy: symptoms, what life expectancy?

THE leukodystrophies are diseases highlighted by the Association ELA, European Association against Leukodystrophies. These serious genetic diseases affect nerve fibers in the brain. According to figures from the ELA association, 3 to 6 children are born each week in France with leukodystrophy, 20 to 40 in Europe.

Definition: what are leukodystrophies?

“Leukodystrophies are genetic diseases that affect the white matter of the brain. This is where all the information carried by the nerves and which come from the gray matter, that part of the brain where information is generated. Nerve fibers cross the white matter where there are also the working cells of the brain, the glial cells. Leukodystrophies are linked to damage to these worker cells whose role is to optimize the functioning of nerve fibers. The glial cells (oligodendrocytes) that synthesize and maintain the myelin sheath, which surrounds certain nerve fibers, are the most fragile. THE consequences on the energy necessary for the propagation of the nerve impulse all make leukodystrophies serious“, develops Pr. Odile Boespflug-Tanguy. Leukodystrophies are considered as rare diseases.

What are the symptoms of leukodystrophy?

The disease can develop at any age of life. “In some children it is during the neonatal or even antenatal period that the symptoms appear. For some leukodystrophies, these symptoms appear at a very late age beyond 60 years. There is no preferential age in the onset of symptoms but the most severe and well-known leukodystrophies are those that affect young children“, explains the neurogeneticist. symptoms are very common in young children, because this is the time of life when the myelin sheaths are developing very actively. “The myelin sheath, affected in leukodystrophies, is made up of lipids. It surrounds the nerves to allow them to work faster, be more efficient and more energetic. During learning and until the beginning of adulthood, we make myelin as soon as we learn something according to a very precise program.“. Thus, in the smallest, the troubles are above all motor, children do not learn to walk, sit up, hold their head or lose what they have learned. The older we get, the more the initial symptoms are emotional and cognitive.. “It can start with difficulties at school or at work. Motor disorders only appear during the course of the disease“, notes Odile Boespflug-Tanguy.

What causes leukodystrophy?

Leukodystrophies are genetic diseases that have different forms of transmission :

• There autosomal recessive form: the disease is transmitted by each parentcarrying a genetic weakness (mutation) on only one of their genetic heritage (DNA). The child is sick because he bears this weakness on both maternal and paternal genetic heritages. These forms are the most common.
• X chromosome abnormality : several leukodystrophies are linked to abnormalities on the X chromosome. carrier men are sick because they have only one X chromosomewomen are not sick or slightly sick because they compensate with their second X chromosome. They are said to be “transmitters or carriers“.
• There dominant form : One parent is ill but has few symptoms. The disease can be transmitted to one of the children who will express more significant symptoms. This variability in disease expressivity makes the diagnosis and prognosis of these forms often difficult.
• There de novo transfer : a child presents a genetic abnormality when neither parent is a carrier abnormality in the analysis of their blood. The genetic abnormality has created during the production of sperm or egg which leads to a mixing and a significant reorganization of the genetic heritage.

“Many patients are follow-up for psychiatric disorders when in reality it is a leukodystrophy that begins”

The diagnosis is usually made on brain MRI which makes it possible to show abnormalities of the normal signal of the white matter. “From the moment the signal is abnormal, the specialist must first determine if the origin of this signal is genetic. And if so, if this genetic abnormality first reaches the white matter and specifically the glial cells“develops the professor of medical genetics. In adultsleukodystrophies are misidentified because difficult to diagnose among many non-genetic white matter diseases. “This is the case for the inflammatory diseases such as multiple sclerosis or vascular diseases of the nervous system...” she specifies. And since in adolescents and adults the symptoms are primarily cognitive and emotional“many patients are follow-up for psychiatric disorders when in reality it is a leukodystrophy which begins“. THE early detection is particularly determining in these diseases because some can benefit from a genetic counseling with antenatal diagnosis or specific treatment. “When we discover leukodystrophy in a patient, we always proceed to a family investigation to check if there is a risk that another family member is at risk of carrying or transmitting the disease.“Some leukodystrophies can progress at full speed and rapidly destroy all white matter as preventive treatments for this degradation can exist. “In these situations, we are concerned about screen in the family children carrying the genetic anomaly before he developed the disease. Because the important thing is to detect the disease as soon as possiblefrom the first motor disorders in toddlers, learning and cognitive disorders in adults“.

What is the treatment for leukodystrophy?

“For a large number of cases, there is no specific treatment yet but care is key. It must be early to delay the consequences of the disease as much as possible and permanently adapted to the difficulties of daily life within the family as well as at school or in the workplace.” recognizes Odile Boespflug-Tanguy. genetical therapywhich raises many hopes, is a recent preventive treatment of the patient’s degradation in certain forms of leukodystrophies with dysfunction of the metabolism of the glial cells of the white matter “It is replace the diseased gene with a normal gene in blood stem cells (hematopoietic stem cells) which will gradually colonize the brain. It is therefore a long process so that the metabolism of the brain is improved, on average one year. The patient must therefore have very few symptoms and a disease that has changed little to observe a benefit. This treatment is therefore only effective if the disease is detected very early, or even before the appearance of symptoms“.

What is the life expectancy of leukodystrophy?

Life expectancy depends on the form of leukodystrophy. “She can be deadly within a very short time, less than a year in very young children. Other forms are very slow : the lifespan is not compromised but the severe handicap worsens over time. In these slow forms, the symptoms of the vast majority of patients worsen on leaving adolescence.“, details the specialist.

Thanks to Professor Odile BOESPFLUG-TANGUY, neuropediatrician-neurogenetician at AP-HP, Coordinator of the Reference Center for Rare Diseases “LeukoFrance”