NEWLY DIAGNOSED

“Here at Cure MLD, we all remember the day we heard the words Metachromatic Leukodystrophy for the first time. We understand how powerful those feelings of fear, grief and rage are. Cure MLD exists because we want to offer support, guidance and hope for you and your family.”

- Maria Kefalas, founder of Cure MLD

There is no denying how challenging the first days and months after diagnosis are, but we promise that you can lead a life that has room for happiness and joy with an MLD diagnosis. We are here to provide information about what metachromatic leukodystrophy is, what treatments exist, and resources you can use. We are here to help. For more information and to contact someone who has been in your shoes, please contact info@curemld.com.

What is Metachromatic Leukodystrophy (MLD)?

Metachromatic leukodystrophy (MLD) is a recessive, genetic disorder caused by a deficiency in the enzyme arylsulfatase A (ARSA). As a result, certain fats, called sulfatides and their associated compounds, build up in the nervous system. These sulfatides are toxic to the white matter, or myelin, of the brain and nervous system. This ultimately creates decline in motor and cognitive functions.

What does it mean to be an MLD carrier?

Carriers for MLD usually have no signs or symptoms of MLD. Being a carrier means that there is one working and one non-working copy of the MLD gene that disrupts ARSA function. Carriers did not do anything to cause their child to have MLD. About 1 in 100 people carry a genetic mutation that can cause MLD but will never suffer from the disease. When two carriers of this mutation have a child, they have a 25% chance of passing both genetic mutations. That child will present with MLD. Those parents also have a 1 in 2 chance of having a child who is an unaffected carrier themselves. Siblings and other family members should be tested if a member is positive for MLD.

How rare is MLD?

Without universal newborn screening, no one knows for sure how rare MLD is. The current estimated incidence of MLD ranges from 1 in 40,000 to 1 in 100,000. Different populations have varying incidence rates. For instance, among the Navajo population, the incidence of MLD is higher than the general population at approximately 1 in 2,500.

How is MLD diagnosed?

The best practice recommendation is to get genetic and biochemical testing completed for a diagnosis. Common biochemical tools are blood and urine testing. MRIs are also frequently used to determine any white matter changes in the brain associated with leukodystrophy (the group of rare, genetic disorders that impact the white matter of the brain) If you need MLD testing for yourself or a family member, you should contact the Lysosomal Storage Diseases Testing Lab at Thomas Jefferson University. For U.S. based participants, Invatae has offered sponsored genetic testing for MLD.

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Late Infantile

Symptom onset: typically at or younger than 2.5 years
Late Infantile MLD (LI-MLD) is the most common form of MLD, representing over 50% of MLD patients
Some common symptoms of Late infantile MLD commonly presents as difficulty walking or lack of walking, impaired or regressed speech, and muscle weakness. It is typical to see a loss of milestones or an inability to reach milestones (for example, walking, talking, reaching / grabbing objects). Parents will typically notice symptoms around when the child begins to walk and gross motor skills are impacted.

Late Juvenile

Symptom onset: 8-16 years
The juvenile subtype (early and late) comprises about 20-30% of MLD patients.
Common symptoms are new difficulties with speech, behavioral or psychiatric problems, loss of muscle tone, or difficulties with balance, coordination, and movement. The late juvenile disease form typically presents with cognitive symptoms before or at the same time as motor decline. Early symptoms can be seen with newly developed problems with school or behavior. It is often misdiagnosed with ADHD or other behavioral conditions.

Adult Onset

Symptom onset: 16+ years
The least common form of MLD, at around 10% of all MLD cases
Adult onset patients are the most varied in terms of symptom presentations and progression of the disease. In general, this form presents as psychiatric or cognitive issues. Common symptoms are changes in behavior, memory, cognition, and balance/mobility skills. Often, the individual will start showing poor school or work performance, may seem anxious, disorganized, and show poor judgment. Although cognitive decline is usually the first to be noticed, some adult onset patients do present with physical decline in the early stages of MLD.

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What are the treatment options for MLD?

We have no cure for MLD, for now, but research and treatment breakthroughs are occurring at a rapid pace.

We are committed to supporting continuing research to treat symptomatic and non-symptomatic patients, to providing resources and newborn screening so that patients are diagnosed as soon as possible to benefit from treatment, and to providing resources to doctors and loved ones caring for those with MLD. Current therapies cannot reverse neurological damage and have mixed results in slowly progressing so unfortunately they are most effective in patients whose symptoms are in the early stages or who have been diagnosed by testing after an older sibling showed symptoms.

There are very effective treatments for pre-symptomatic children, including gene therapy, (New promise of Gene Therapy) and there are a growing number of treatment options for symptomatic patients. One such treatment was an experimental enzyme replacement therapy (ERT). At the start of 2021, Takeda Pharmaceuticals finished recruiting late-infantile MLD individuals for their ERT clinical trial. The trial is now closed and they are no longer accepting participants.

Gene therapy to treat MLD is being advanced by Orchard Therapeutics. They are now treating individuals either commercially in Europe or through their pre-approval access policy (sometimes called "compassionate use") on a case by case basis in the United States. Just recently, they also opened up a late-juvenile arm for their clinical trial (you can find out more about the eligibility criteria here). Orchard's gene therapy has mostly been used to treat pre-symptomatic late-infantile MLD and select early juvenile patients. Often, patients who have undergone the treatment were diagnosed before showing any symptoms of MLD. At this time, the majority of children treated have been the younger siblings of children diagnosed with late-infantile onset MLD. For any questions about eligibility, a treating physician should reach out to medinfo@orchard-tx.com for more information. At the end of 2020, Orchard's MLD gene therapy treatment (called Libmeldy) received EMA approval in Europe, and at the end of 2022 or early 2023, we expect them to seek approval with the FDA in the US. There is also a clinical trial in China that provides gene therapy to patients. You can learn more about the work of Shenzhen Geno-immune Medical Institute (GIMI), Shenzhen, China by contacting Dr. Lung-Ji Chang at the Shenzhen Geno-immune Medical Institute (GIMI) at c@szgimi.org. Please note Cure MLD has not referred patients to this trial and there is no published data on the effectiveness of this treatment.

Bone marrow and stem cell transplants have been used around the world for at least two decades to treat pre-symptomatic patients and those with little disease progression. Because they typically use more aggressive chemotherapy and have mixed results in stopping disease progression, many patients prefer gene therapy if they qualify for a clinical trial. These transplants are currently the only treatment option available for some older MLD patients. We expect to see more treatment options for adult patients very soon.

Since these treatment options are still only clinical trials, you should have your doctors reach out to the researchers to determine if your loved one meets eligibility criteria. Sadly, not all patients will get to participate, but our community is grateful for the fact that these clinical trials are available and represent such hope and progress for people living with MLD.

You can find more information on treatment options on the Support and Resources page or by clicking on any of the links above.

For MLD patients who are not elgible for gene therapy and want to learn more about a bone marrow or stem cell transplant, we recommend you contact Dr. Maria Escolar at the Children’s Hospital of Pittsburgh, Dr. Joanne Kurtzberg at Duke University Medical Center, or Dr. Paul Orchard at the University of Minnesota to learn more about these treatment options for your loved one. If you pursue a bone marrow or stem cell transplant, we can arrange for a family who has undergone such treatments to contact you and share their experiences.

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I just found out that I or a loved one has MLD. What’s going to happen?

MLD varies depending on different ages and different levels of progression. For more information on the MLD subtypes check out LINK. We cannot predict how MLD will progress in your child. We are not medical professionals and we do not intend to replace the medical advice of a doctor experienced with treating MLD. We can direct you toward information and clinical trials / treatments as they apply. We have resources on Cure MLD that will help you learn about others’ experiences and what clinical trials are available but each and every case will be different depending on the age of the patient and how advanced the disease is. Only a doctor with extensive experience with MLD will be able to give you a good idea of what your loved ones specific progression may be.

Getting information:

One of the fastest ways to learn about MLD and treatment options is to enroll in the MLD natural history study at the Children’s Hospital of Philadelphia (CHOP).

There is no travel or cost associated with the natural history study. Sharing your medical records with specialists at CHOP (who work with pediatric and adult patients) can help answer your questions and get you access to resources and information you need to help your loved one impacted by MLD.

CHOP Leukodystrophy Center

Online Referral Survey

MLD Natural History Study

You are not alone, please contact us and we will have a family ambassador contact you.

We will also send you and your loved one a special care package that includes Loie’s Disease, a children’s book to explain leukodystrophy to children, and the “Living with Leukodystrophy” medical resource guide.