What is RTD?

Riboflavin Transporter Deficiency (RTD) is a debilitating, life-shortening, neurodegenerative genetic disorder. Formerly known as Brown-Vialetto-Van Laere (BVVL) or Fazio-Londe (FL) syndrome, an estimated one in 1 million people worldwide are born with RTD, which means a child with RTD is potentially born every few days.  Approximately 50% of individuals with RTD develop symptoms before 3 years of age, with 95% developing symptoms under the age of 20.  First reported in 1894 as an “infantile” form of ALS, RTD affects motor and sensory nerve cells (neurons), taking away a person’s ability to hear, see, move, walk, eat and breathe.

There are 2 types of RTD - Type 2 and Type 3. RTD Type 2 is caused by a mutation of the SLC52A2 gene. RTD Type 3 is caused by a mutation of the SLC52A3 gene. These genes are responsible for providing instructions for making specific riboflavin transporter proteins in the body that play an essential role in transporting riboflavin (vitamin B2) across cell membranes. These riboflavin transporters are found in tissues throughout the body, and their malformation in RTD has widespread effects.

curertd.org

RTD is characterized by a loss of certain nerve cells in the spinal cord and brainstem called motor and sensory neurons.  The loss of motor neurons in RTD leads to progressive weakness and wasting (atrophy) in muscles, including those muscles used for movement, breathing, and swallowing. Sensory neurons are nerve cells responsible for receiving information such as sound, sight, touch, etc. from the sensory organs (i.e. ears, eyes) and transmitting this information to the brain. The loss of sensory neurons in RTD can lead to issues including hearing loss, vision loss and gait ataxia (unbalanced walking).

Prior to the onset of symptoms, individuals with RTD have normal development. An infection or fever often precipitate the initial onset of symptoms. If left untreated, RTD results in a progressive decline that is fatal in over 50% of individuals, with death from respiratory insufficiency occurring within 10 years of the onset of symptoms. The exact symptoms, age of onset, severity, and rate of progression are highly variable, even among siblings. 

curertd.org

Frequently Asked Questions

  • RTD is an autosomal recessive disorder. In order for an individual to be affected, they must receive a copy of the mutated gene from BOTH parents. (see photo)

  • High dose riboflavin (vitamin B2) has been used as a life-saving treatment for RTD and can potentially prevent irreversible damage. However, it is not a cure. Although some individuals with RTD have shown dramatic and prolonged improvement with riboflavin treatment alone, others have shown signs of continued neurological deterioration after starting riboflavin treatment,

    There have been at least eight people (6 children and 2 adults) with RTD on riboflavin treatment who died as a result of RTD complications between 2014 and 2024.

    • Hearing loss

    • Muscle weakness

    • Pontobulbar palsy, which may cause feeding and speech difficulties

    • Respiratory compromise resulting from weakness in the muscles involved in respiratory function

    • Vision loss

    • Sensory gait ataxia (wide-based, unbalanced walking). Sensory abnormalities may also cause a loss of sensation for pain and touch

    • Autonomic dysfunction (difficulties regulating temperature, excessive sweating, sleep disturbances, GI issues)

    • Aggressive scoliosis

    • General fatigue

    • Seizures (very rare)

    • Breath-holding spells / blue spells

    • Restless leg syndrome / leg thrashing during sleeping

    • Ptosis (drooping eyelid)