Cure RTD

Today, we remember Brooklynn, four years after her passing from complications related to RTD.

Brooklynn faced more in her life than any child should, but she did so with remarkable strength, joy, and spirit. She left a lasting mark on everyone who knew her, and her story continues to be part of the work we do in the RTD community.

We are also deeply grateful to her parents, Vanessa and Paul, for the love, advocacy, and commitment they have shown over the years. Through their awareness efforts and past fundraisers for Cure RTD, they have helped carry Brooklynn’s legacy forward in a way that continues to make a difference.

E is for Ectoenzymes

Riboflavin (vitamin B2), is essential fuel for our cellular engines. But most flavins in the bloodstream do not travel as free riboflavin. Instead, about 90% circulate as larger molecules called FAD and FMN.

These forms are too bulky and too charged to slip through the cell membrane, and riboflavin transporters, known as RFVTs, cannot bring FAD or FMN into the cell.

So how does the cell access riboflavin?

RFVTs can transport free riboflavin outside the cells that is in blood or brain fluid. But FAD and FMN may also play an important role in supplying riboflavin to cells, as long as they are converted first.

That is where ectoenzymes come in.

Ectoenzymes sit on the outside surface of cells and act like molecular scissors. Between 2022 and 2024, researchers first discovered that these enzymes help convert FAD and FMN into free riboflavin, allowing cells to take it up. Until recently, the purpose of the large amounts of FAD and FMN in the blood and brain was not understood.

First, NT5E, ENPP1, and ENPP3 help convert FAD into FMN. Then ALPL removes the final phosphate group from FMN, turning it into free riboflavin.

This provides additonal free riboflavin for the RFVT transporters to pull into the cell.

This may matter in Riboflavin Transporter Deficiency (RTD). In RTD, the RFVT transporters are already impaired, which means cells depend even more on having enough free riboflavin available at the cell surface.

One fascinating question is whether the distribution or regulation of these ectoenzymes might play a role in why certain tissues are affected more than others in RTD. Cells have very different mixes of ALPL, NT5E, ENPP1, and ENPP3.

This is one of many important questions Cure RTD-funded research is working to answer. Understanding this process could open a new window into RTD biology and may help point toward future treatments.

For RTD, these tiny enzymes on the outside of cells may turn out to be another important piece of a much larger puzzle.

D is for DNA 🧬

Think of DNA as the body’s instruction book, written in a code made from just four letters: A, C, G, and T.

That instruction book is huge. The human genome has about 3 billion DNA letters, tucked inside almost every cell in your body. Within those billions of letters are around 20,000 genes, including two genes connected to Riboflavin Transporter Deficiency (RTD): SLC52A2 and SLC52A3.

These genes may be small, but they have an important job. They help provide the instructions for making riboflavin transporters, which move riboflavin (vitamin B2), into cells where it’s needed.

The SLC52A2 gene is only 7,152 DNA letters long, just a tiny fraction of the full 3-billion-letter genome. But when even one letter in this gene, or in SLC52A3, is changed, the instructions can stop working properly.

That means RTD can be caused by something as tiny as a single DNA “typo.”

One wrong letter out of 3 billion.

It’s amazing, and heartbreaking, that such a small change can have such a big impact on the body.

In theory, fixing that one DNA letter could help treat, or even cure, RTD. But that exciting story is coming later in “G is for Gene Therapy.” 🧬✨

June is Deafblind Awareness Month 🌍💙

For many people living with Riboflavin Transporter Deficiency, RTD can cause both severe hearing and vision loss. As a result, some individuals with RTD are legally deafblind and navigate challenges that are often invisible to others.

Deafblind Awareness Month helps shine a light on dual sensory loss while also honouring Helen Keller, who was born in June and remains an enduring symbol of strength and advocacy.

👂 Many individuals with RTD use cochlear implants to support hearing.

👁️ Vision loss caused by optic atrophy cannot be corrected with glasses.

This month, we’re raising awareness for the RTD community and recognizing the strength of those living with dual sensory loss.

Together, we can help more people understand the realities of RTD and support families affected by this rare disease.

C is for Cochlear Implant 💙

Hearing loss is one of the most common symptoms of Riboflavin Transporter Deficiency (RTD).

In RTD, hearing loss usually starts in childhood and can range from moderate loss to profound deafness. It is caused by auditory neuropathy, meaning the ear may detect sound, but the signal does not travel clearly through the auditory nerve to the brain. Because of this, speech can be hard, or even impossible, to understand, even in some people with only mild hearing loss.

Hearing aids often provide little or no benefit for RTD-related hearing loss because they mainly make sounds louder, but they do not make speech clearer.

A cochlear implant works differently. Instead of simply amplifying sound, it turns sound into electrical signals that help stimulate the hearing nerve, giving the brain clearer access to sound information.

For many people with RTD, that difference can be life-changing.

Across the RTD community, more than 150 people have received cochlear implants. Outcomes can vary, but many people report meaningful improvements in access to sound and speech understanding.

For people affected by RTD, a cochlear implant can be more than a device. It can be a pathway to language, connection, and greater independence.

Learn more on the Cure RTD hearing loss page:
https://curertd.org/what-is-rtd/hearingloss/

B is for Brown-Vialetto-Van Laere Syndrome (BVVL)

Before Riboflavin Transporter Deficiency (RTD) became the more widely used name, many people were diagnosed with Brown-Vialetto-Van Laere Syndrome, or BVVL.

The name comes from the doctors who first described the condition in the medical literature. Charles Henry Brown reported the disorder in 1894, followed by Vialetto in 1936 and Van Laere in 1966.

For many years, BVVL was recognized by its symptoms, including progressive hearing loss, cranial nerve problems, muscle weakness, breathing difficulties, and bulbar symptoms that affect speech and swallowing. However, the cause of the disease was unknown and no treatment was available.

A major breakthrough came in the early 2010s, when researchers discovered that many people diagnosed with BVVL had changes in the SLC52A2 or SLC52A3 genes. These genes provide instructions for making riboflavin transporters, which help move riboflavin (vitamin B2), into cells. This discovery led to a new and more accurate name: Riboflavin Transporter Deficiency, or RTD.

That discovery changed how the disease is understood. The name BVVL remains an important part of RTD history and is still used by some doctors, but RTD better explains what is happening in the body and points toward treatment.

B is for Brown-Vialetto-Van Laere Syndrome, a historic name that helped lead to today’s understanding of RTD.

Starting today, we’re highlighting the A to Z of Riboflavin Transporter Deficiency. Every week, we’ll share a new fact about RTD.

Today’s post is A is for Aspiration.

Aspiration happens when something such as food, liquid, saliva, or stomach contents enters the airway or lungs. Many people describe this as food or drink “going down the wrong pipe.”

For people with RTD, aspiration can be a serious concern. RTD can affect the nerves and muscles involved in swallowing, speaking, breathing, and airway protection. This means some people with RTD have trouble swallowing safely, which can increase the risk of food, liquid, or saliva entering the lungs.

Over time, aspiration can lead to repeated chest infections, pneumonia, lung inflammation, and breathing complications. In severe cases, aspiration can become life-threatening, and a small number of people with RTD have tragically passed away following aspiration-related accidents.

To reduce this risk, some individuals with RTD use feeding tubes, thickened drinks, softer foods, special positioning, or swallowing techniques recommended by their medical team. These supports can make eating and drinking safer and help protect the lungs.

For many RTD families, something as simple as a meal can require planning, care, and constant awareness.

A is for Aspiration, one of the many daily challenges that can come with RTD.

While Cure RTD remains focused on better treatments and ultimately a cure for RTD, we are also continuously reviewing therapies that could help improve the damage already caused by the disease.

One promising therapy Cure RTD has on our radar is apitegromab, a drug designed to target muscle weakness.

Apitegromab was developed for spinal muscular atrophy, or SMA, where progressive motor weakness is a major feature. It works by blocking myostatin, a natural protein that limits muscle growth and strength. The goal is to improve muscle function, not to treat the underlying genetic cause of SMA (or RTD).

That is why this drug is interesting for RTD.

SMA and RTD are different diseases, but both can leave patients with significant motor weakness, even after treatment. In SMA, weakness comes from loss of motor neuron input to muscle similar the RTD. This overlap gives hope that a drug improving muscle strength in SMA could potentially provide benefit for some RTD patients as well.

The FDA (USA) and EMA (Europe) have accepted the apitegromab application for approval with the drug launch to SMA patients expected later this year.

Apitegromab has not yet been studied or approved for RTD. With the approval and launch, Cure RTD will be able to fund research studies with RTD patients to see whether this approach could help improve strength, mobility, breathing reserve, hand function, or quality of life in RTD patients living with residual weakness.

This is not a cure for RTD, but it may be one more door opening.

Three year old Rosa from the UK is living with RTD Type 3, and her family is showing what love in action looks like.

A huge congratulations to Rosa’s dad, Daniel Norman, and her aunt, Daisy Stratford, who completed the Three National Peaks yesterday, climbing the highest mountains in Scotland, England, and Wales in just 24 hours.

They raised thousands for RTD research and more than doubled their fundraising goal.

What an incredible accomplishment, and what a powerful way to support Rosa, the RTD community, and the research that brings hope for the future.