Frequently Asked Questions

Right now, you might feel like you have more questions than there could ever be answers. We’re here to help with answers to some of the most commonly asked questions by families affected by 4H Leukodystrophy.

Remember—you’re not alone at any point on this journey. We’re on hand to provide any answers or support that you don’t find here. Just reach out.

What is 4H Leukodystrophy?

4H Leukodystrophy (4HL) belongs to a larger group of conditions called leukodystrophies. These diseases affect the white matter of the brain and damage the myelin sheath, which surrounds and protects the nerve cells in the brain and spinal cord and assists with transmission of messages between cells. Hypomyelination is a common sign of a leukodystrophy, and this means that the body is unable to produce these myelin sheaths at normal levels. In 4H Leukodystrophy, symptoms of hypomyelination, hypodontia, and hypogonadotropic hypogonadism (the 4Hs) are usually present.

What causes 4H Leukodystrophy?

4H Leukodystrophy is caused by genetic changes (called variants) that are present in all the cells of the body. These variants are in one of four genes: POLR3A, POLR3B, POLR1C, and POLR3K and cause the gene to not work properly. It is likely that more genes will be linked to 4H Leukodystrophy as researchers learn more.

How did this happen?

We all have two copies of every gene; one is inherited from each parent. 4H Leukodystrophy is inherited in an autosomal recessive manner. This means that each parent, both mom and dad, passed down a non-working copy of a POLR3 gene to their affected child. The parents themselves are not affected because each still has a working copy of the POLR3 gene in addition to their non-working copy. They are called “carriers” of 4H Leukodystrophy.

Did anything I do cause my child to have 4H leukodystrophy?

No. We have no control over the genetic material that we pass down to our children. Since genes are randomly passed down to children, neither parent is at fault for their child’s condition. Additionally, most people have no way of knowing they are a carrier until and unless they have an affected child.

How common is 4H Leukodystrophy?

As is the case with many rare genetic conditions, the prevalence of 4H Leukodystrophy is unknown. Although there are approximately 300-600 known patients, there are likely many more who are undiagnosed. As genetic testing technology continues to expand, we hope many more families will find a diagnosis and appropriate care.

What is POLR3-Related Leukodystrophy? Is it the same as 4H Leukodystrophy?

Yes, POLR3-Related Leukodystrophy is a newer term for 4H Leukodystrophy. 4H Leukodystrophy is the term that was adopted to describe patients before we understood the genetic basis of the disease. POLR3-Related Leukodystrophy was introduced once it was discovered that variants in the POLR3 genes are responsible for the condition. You can use either name interchangeably.

If we have one child with 4HL, can additional children have 4HL?

Yes, because 4HL is inherited from both parents, there is a chance a future child between you could also be affected. For each pregnancy, there is a 25% (1 in 4) chance your child will be affected, a 50% chance your child will be a carrier and a 25% chance your child will be unaffected and not a carrier. Many families find it helpful to meet with a genetic counselor to discuss this risk and reproductive options available to them. You can find a genetic counselor here.

What are the implications for other family members?

As for all inherited conditions, genetic counseling is recommended for close family members including your child’s siblings. Other family members such as aunts, uncles, and cousins may also benefit from genetic counseling and genetic testing to look for non-working copies of POLR3 genes. Some relatives could be carriers of 4HL, which wouldn’t affect their health, but would be important to know as they plan their own families.

Who should we add to our care team?

In general, our families find gastroenterology and orthopedic surgeons to be essential to the care team. Gastroenterologists help monitor weight and place feeding tubes when necessary. They can also assist with constipation (often an ongoing issue for 4HL patients) and are often the most visited specialist. The orthopedics team will help with gait and bone issues, including hip dislocations/displacements.

It will also be necessary to add to your care team a neurologist, pulmonologist, ophthalmologist, endocrinologist, and rehabilitation specialists to help with speech, physical, and occupational therapy.
All specialists, in addition to your general pediatrician, will be critical in helping your child reach their fullest potential and will monitor their health as they grow.

You may find it helpful to download and bring along this Letter to Providers on your first visits.

How do we stay organized with all of these specialists?

If you have not yet seen a geneticist and/or genetic counselor, it is highly recommended you ask your pediatrician about this as soon as possible. They will be immensely helpful in coordinating care with the different specialties. The Leukodystrophy Care Network (LCN) is a great place to find a genetic counselor or geneticist team who specialize in 4HL. This network consists of certified centers that focus on leukodystrophies to provide well-researched and customized care.

Who are the experts on 4HL?

The Yaya Foundation has found the expertise of Dr. Geneviève Bernard, Dr. Adeline Vanderver, and Dr. Nicole Wolf to be monumental for our 4HL families. These experts in 4H Leukodystrophy can answer your specific questions, and they also hold talks frequently to discuss the ongoing research and recent findings for 4HL care.

Why is my child’s experience with 4HL so different from others?

It can be confusing to read scientific articles or connect with other parents that describe patients who are very different from your child. Every individual’s experience with 4HL is unique. The severity and outcome can be highly variable. 4HL can cause a child to rapidly lose their abilities or slowly regress. In general, if children present with symptoms earlier on such as in infancy, deterioration is expected to happen more quickly. Some children express frustration at their inability to function as they were able to previously. Because so few cases have been reported, and no two cases are exactly the same, it is most important that you seek specialized care from a physician recognized as an expert on 4H Leukodystrophy or at a center with experience treating patients affected by leukodystrophies.

What should our support system look like?

These pivotal points in your child’s development can be very emotionally heavy as a caregiver. As your child grows, it will be important that as parents, you also have a strong support system. A social worker can help obtain services and navigate financial and social barriers. Many families benefit from psychological support from a therapist or other licensed professional. You should prioritize your own health and wellness as much as possible to be the best caregiver you can be. Consult your specialists or general physician for more information.

How else can we help our child maximize their potential?

As your child continues to develop, keep the recommendations from their specialists and your genetics team in mind. That said, you do know your child the best, so don’t be afraid to ask for personalized recommendations from your specialists. As a parent, you can be a powerful advocate for your child. At the same time, your child is not their condition and their continued well-being can be supported in many other ways. Continue to read to them, play with them, and encourage peer to peer contact. If your child has difficulty with verbal communication, for example, some parents find it helpful to communicate via American Sign Language or visual aids.

Is there treatment for 4HL?

Right now, there is no targeted therapy or cure for 4H Leukodystrophy. Symptoms are treated and managed with supportive care. Researchers are actively searching for new possibilities to treat the disease directly. For more specific information, you can access the resource library here.

What is the most current research on 4HL?

The clinical providers and experts are the top leaders in 4H Leukodystrophy research. However, 4H Leukodystrophy has only been recognized as a condition in the last two decades. Researchers are still uncovering how the changes in the POLR3 genes causes the disorder and are currently trying to find targeted therapies or treatments. The Yaya Foundation supports several initiatives including the development of a disease model using cells or mice to test future potential therapies as well as early-stage gene therapy research. To view our latest research, visit our Research Library. You can support these initiatives and accelerate the research by participating in our Data Collection Program.

Where can I go for other resources?

Facebook Groups/Pages

POLR3 Caretakers/4H Leukodystrophy
A private Facebook Group helpful for sharing and receiving resources with and from other families. According to some 4HL families, this is most helpful when newly diagnosed.

Yaya Foundation for 4H Leukodystrophy
A Facebook Page for status and progress updates of the organization. Here you will be able to find the newest research, connect to other 4HL families, join fundraising efforts, and stay informed on the latest Yaya Foundation innovations.

Yaya Foundation for 4H Leukodystrophy blog/updates
More detailed information on upcoming events such as #4HLFamily calls, research updates, and more.

Living with Leukodystrophy eBook
The Calliope Joy Foundation, an incredible organization focused on curing leukodystrophies, partnered with the world’s leading leukodystrophy specialists to create a guide for caregivers, nurses, and doctors. The Calliope Joy Foundation has generously given The Yaya Foundation permission to share this eBook for free.

Make-A-Wish Foundation
Some of our families have found this foundation to be an invaluable resource to provide their children with memorable experiences in-between appointments and continuing care. For more information regarding this resource, visit their website here or search the Facebook group listed above.

Courageous Parents Network
A platform that offers support to families caring for children with serious illnesses/conditions. Parents are able to reach out to other families to either offer or provide advice and care tips. Not specific to 4HL but can easily be used for more general care.

For US families, as you navigate the Medicaid journey it can be useful to work with a complex care pediatrician or primary care pediatrician who works with medically complex children to help file the proper paperwork.  To learn more about advocating for your child and Medicaid, you might find it useful to go to Family Voices and learn more about resources in your state.  Be prepared to be diligent, applying for Medicaid is often challenging.

Since each US state has different policies and procedures for applying to Medicaid, check out the website Kid Waivers to learn about the guidelines for your home state so you can get started.

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