Información general sobre la enfermedad
Otros nombres
- ARSA deficiency
- Arylsulfatase A deficiency disease
- Leukodystrophy - metachromatic
Tipo de enfermedad
Prevalencia al nacimiento
- It is estimated that more than 30 babies are born with this condition each year in the United States.
- Visit GeneReviews to learn more about how often this condition occurs.
Resultado del examen
¿Qué es metachromatic leukodystrophy?
Metachromatic leukodystrophy (MLD) is an inherited (genetic) condition that causes damage to the brain and other organs.
The brain is the control center of the body. The brain is made up of individual cells called neurons. Neurons send electrical signals to different parts of the body through nerves. These electrical signals contain instructions for how the body should operate. Just like an electrical wire needs insulation, these nerve wires are wrapped in a protective fatty layer called myelin (white matter). An important part of myelin is sulfatides, a chemical which needs to be continuously recycled by an enzyme, arylsulfatase A (ARSA). This process takes place in lysosomes, the recycling centers of your cells. When there is not enough ARSA enzyme, the sulfatides, start to build up. This build-up can cause damage to the nerves and other parts of the body.
There are two main types of MLD based on when they begin to cause signs and symptoms: early onset and late onset.
Early-onset occurs in babies and children and includes two subtypes: Late Infantile and Early Juvenile.
- The Late Infantile subtype is the most common form of MLD. It typically begins before 2 ½ years (30 months) of age.
- The Early Juvenile subtype typically begins between 2 ½ years (30 months) and 7 years of age.
Late-onset occurs in older children and adults and includes two subtypes: Late Juvenile and Adult.
- The Late Juvenile subtype typically begins between 7 and 16 years of age
- The Adult subtype typically does not show symptoms until after 17 years of life.
Examen de recién nacidos y seguimiento
Newborn screening for metachromatic leukodystrophy is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures the level of sulfatides in your baby’s blood. Newborn screening looks for specific sulfatides known as C16:0 and C16:1-OH. Screening will also measure how much ARSA enzyme is in your baby’s blood.
In MLD, babies will have high sulfatide levels and low levels of ARSA enzyme.
In some cases, screening may also look at the gene (ARSA) that causes MLD.
If your baby’s blood spot screening result for MLD is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood or urine tests
- DNA testing using a blood or cheek swab sample
You should complete any recommended follow-up testing as soon as possible. Without diagnosis and treatment, babies with this condition will have serious health problems. If left untreated, most children with the early-onset form will die in childhood.
False-positive newborn screening results for this condition can happen. In rare cases, babies may have a positive newborn screening result for MLD, but actually have a different disease called multiple sulfatase deficiency or saposin B deficiency.
Detalles de la enfermedad
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your baby’s health care provider quickly. It is important to follow their instructions. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
In early-onset MLD, the first signs of the condition in toddlers may include:
- Loss of skills (milestone regression) or failure to gain new developmental skills. This often includes the inability to learn to walk or new difficulty with walking.
- Changes in ability to move eyes (strabismus or esotropia)
In late-onset MLD, the first signs of the condition in older children or adults may include:
- Behavior changes
- New difficulties at school or work
A change in the ARSA gene causes MLD. The ARSA gene gives your body instructions for making the ARSA enzyme protein that helps break down sulfatides.
A changed ARSA gene prevents the cells from breaking down sulfatides properly. When these sulfatides are not broken down, they become toxic and cause the breakdown of myelin. When myelin is destroyed, nerve cells are no longer protected. The nerve cells are then unable to send important nerve signals throughout the body.
MLD is a genetic condition. Babies inherit it from their biological (birth) parents. To learn more about genetic conditions, visit MedlinePlus Genetics.
- MLD is an autosomal recessive Babies inherit the condition when each parent passes down a nonworking ARSA gene to their baby. Only babies with two nonworking ARSA genes—one from the mom and one from the dad—have this condition. People with one working copy and one nonworking copy of the ARSA gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the ARSA gene, they have a 1 in 4 chance of having a child with MLD.
- Carriers for MLD often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with MLD.
- Parents who already have a child with MLD still have a 1 in 4 chance of having another child with MLD. This 1 in 4 chance stays the same for all future children.
Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with MLD. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomicsto find a medical geneticist.
Tratamiento y manejo
It’s important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to replace the missing enzyme and to prevent damage to the brain.
Depending on the different form of MLD (early or late onset), there are different treatment options. Babies with early-onset MLD may be offered gene therapy treatment known as arsa-cel, which can stop or slow disease when given early in life. The target is for children to be evaluated by a qualified MLD gene therapy center by 2-3 months of age. Bone marrow transplant is standard of care for late onset MLD.