Cure RTD

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.

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/