Riboflavin Transporter Deficiency

Disease Overview

Summary

Riboflavin transporter deficiency (RTD), formerly Brown–Vialetto–Van Laere syndrome or Fazio Londe syndrome, is an inborn error of riboflavin transport characterized by progressive neurodegenerative symptoms if left untreated.

Symptoms can include breathing difficulties, facial weakness, hearing loss, abnormalities with the eyes, difficulty chewing and swallowing, muscle weakness of the arms and legs and an unsteady or unbalanced way of walking (abnormal gait). Symptoms become progressively worse if untreated. Intelligence is not affected by this disorder.

RTD is classified in two main subtypes, riboflavin transporter deficiency type 2 (RTD2), when the disease is caused by variants in the SLC52A2 gene and riboflavin transporter deficiency type 3 (RTD3), when the disease is caused by variants in the SLC52A3 gene. Riboflavin transporter deficiency type 1 (RTD1), a much rarer subtype, is caused by a variant in the SLC52A1 gene. These genes are involved in the transportation of riboflavin in the body.

Inheritance for subtypes 2 and 3 is autosomal recessive. Inheritance for subtype 1 is autosomal dominant.

Half of the people with this condition have blood exams showing low flavin levels and abnormal acylcarnitine profiles and urine exams showing abnormal organic acid analysis. However, a definitive diagnosis can only be made by genetic testing identifying causative gene variants.

Riboflavin is a vitamin (vitamin B2) essential for proper health and development of the body. Riboflavin is not readily synthesized in the body and must be obtained through the diet. Although there is no cure, timely treatment with high dose oral riboflavin stops disease progression and can be lifesaving. The long-term prognosis varies depending largely on how early treatment begins.

Introduction

Riboflavin transporter deficiency was previously referred to as Brown-Vialetto-Van Laere (BVVL) syndrome and Fazio-Londe syndrome, named after the physicians and researchers who first described the condition. The term Fazio-Londe syndrome was used for people who had similar symptoms but did not develop hearing loss. The use of these different names can be confusing for patients and caregivers.

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Synonyms

• Brown-Vialetto-Van Laere syndrome
• Fazio-Londe syndrome
• riboflavin transporter deficiency neuronopathy

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Subdivisions

• riboflavin transporter deficiency type 1 also known as:
  • RTD1-related riboflavin transporter deficiency
  • SLC52A1-related riboflavin transporter deficiency
  •  maternal riboflavin deficiency
• riboflavin transporter deficiency type 2 also known as:
  • Brown-Vialetto-Van Laere syndrome 2
  • RFVT2-related riboflavin transporter deficiency
  • SLC52A2-related riboflavin transporter deficiency
  • riboflavin transporter deficiency, type 2; RTD2
  • riboflavin transporter deficiency 2
  • RTD2
  • spinocerebellar ataxia with blindness and deafness 2; SCABD2
  • autosomal recessive spinocerebellar ataxia 3; formerly
  • SLC52A2-related disorders
• riboflavin transporter deficiency type 3 also known as:
  • Brown-Vialetto-Van Laere syndrome 1
  • RFVT3-related riboflavin transporter deficiency
  • SLC52A3-related riboflavin transporter deficiency
  • RTD3
  • bulbar palsy, progressive, with sensorineural deafness
  • pontobulbar palsy with deafness
  • SLC52A3-related disorders
  • Riboflavin transporter deficiency 3

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Signs & Symptoms

The onset of signs and symptoms of riboflavin transporter deficiency (RTD) can range from infancy to early adulthood, but in most people, symptoms start within the first few years of life. Infants and children often develop normally until symptoms begin. Sometimes an infection or fever will occur just before symptoms begin. The disease course in infancy is rapidly progressive and lethal when left untreated. However, onset of symptoms, often with a slower rate of progression, can occur later in life, well into adulthood.

The specific signs and symptoms that may develop and their severity and progression can be very different from one person to another, even among members of the same family, but for most people, the first symptom is sensorineural deafness (hearing loss due to inner ear damage). Generally, the later the onset of symptoms, the milder the disorder is. Severe forms can progress quickly and without treatment can be life-threatening.

Signs and symptoms may include:

• Pontobulbar palsy, which refers to paralysis of a specific region of the brainstem, the part of the brain that connects to the spinal cord and includes several cranial nerves (especially cranial nerves IX and X) that help to control facial expressions, hearing and balance, taste, and the muscles used to move the head, shoulders and the tongue. Pontobulbar palsy may cause:
  • Weakness of facial muscles and reduced facial expressions
  • Difficulty chewing and difficulty swallowing (dysphagia) that can lead to feeding difficulties in infants, and a risk of aspiration, in which food, fluid or other foreign material accidentally goes into the lungs
  • Slurring of speech or difficulty forming words (dysphonia)
  • High-pitched wheezing sound when breathing (stridor)
  • Brief, spontaneous contractions (fasciculations) of the tongue and weakness of tongue which can contribute to swallowing difficulties
  • Difficulties with chewing and swallowing
• Breathing (respiratory) problems which may be one of the first signs when the disorder begins in infancy and may result from paralysis of the diaphragm, a muscle that separates the chest cavity from the abdominal cavity
  • When taking in a breath, the diaphragm contracts and moves downward, which increases the space in the chest cavity and allows the lungs to expand when filled with air
    • Respiratory failure caused by denervation of the diaphragm is the main cause of death in people with RTD
  • Sensorineural hearing loss of varying degrees of severity is the earliest and most common symptom
    • Sensorineural hearing loss occurs when the nerves within the ear cannot properly send sensory input (sound) to the brain; it is not caused by problems with the ear itself
  • Visual loss of varying degrees due to degeneration of the main nerve of the eyes (optic nerve) that sends sensory input from the eye to the brain to form images (optic atrophy)
  • Rapid, involuntary movements of the eyes (nystagmus)
  • Drooping of the upper eyelids (ptosis) in a few people

In addition, RTD causes damage to the nerves outside the brain and spinal cord (peripheral neuropathy) that leads to:

• Weakness and degeneration (atrophy) of the upper arm muscles (those between the elbow and the shoulder) which may become progressively worse and affect the entire arms and legs
• Weakness of certain muscles of the neck which may be followed by weakness and degeneration of the muscles of the trunk
• Ataxia, in which there is a lack of control over muscle movement coordination and may lead to an uncoordinated or unsteady manner of walking (abnormal gait)
• Respiratory insufficiency, when the phrenic nerve which controls the diaphragm is weakened, leading to difficulty breathing and may require ventilatory support

There may also be:

• Muscle weakness leading to intolerance of exercise or extended activity
• Muscular contractures, a condition where muscles become permanently shortened and tightened, leading to reduced flexibility and difficulty moving the affected joint
• Vocal cord paralysis, when one or both vocal cords (vocal folds) are unable to move properly due to interrupted nerve signals and can cause voice changes and breathing problems

There are differences between riboflavin transporter deficiency types 2 and 3.

• Type 2 is characterized by muscle weakness that is most prominent in the arms and neck, while in type 3 muscle weakness is more generalized.
• Vision loss, optic atrophy and sensory ataxia are more common in type 2 whereas vocal cord paralysis is more common in type 3.

Type 1 (the rarer form) shows up in babies and is characterized by the following signs and symptoms:

• Seizures
  • Generalized tonic-clonic, where the baby’s whole body stiffens and then jerks rhythmically, or
  • Focal tonic-clonic, where only one part of the body (an arm or a leg, for example) does the stiffening and jerking.
• Metabolic acidosis, a condition where there is too much acid in the blood, can make the baby breathe very fast or seem unusually tired
• Hyperammonemia, an increased level of ammonia in blood, can irritate the brain and lead to symptoms like sleepiness, poor feeding, or even more seizures

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Causes

Riboflavin transporter deficiency is caused by changes (variants) in certain genes that are involved in the transportation of riboflavin. Riboflavin, also known as vitamin B₂, is a water-soluble nutrient that the body cannot produce on its own, so it must be obtained through foods such as milk, yogurt, eggs, meats and fortified grain products. After eating these foods, riboflavin is absorbed through the lining of the gut and carried by special “transporter” proteins into the bloodstream and from there it travels into every cell. Once inside, riboflavin is converted into two essential helper molecules, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act as coenzymes. Coenzymes are non-protein compounds that are necessary for the proper function of enzymes, which are specialized proteins that cause (catalyze) biochemical reactions in the body. These two coenzymes are essential for maintaining the body’s energy supply, the growth, development and function of cells, and the metabolism of carbohydrates, fats and proteins.

Scientists have identified three closely related riboflavin transporter proteins; each produced from a specific gene.

• RFVT-1 is encoded by the SLC52A1 gene and is most active in the placenta (organ that connects mother and fetus) and in the developing gut of the newborn.
• RFVT-2, encoded by the SLC52A2 gene, is found virtually throughout the body’s tissues.
• RFVT-3, encoded by the SLC52A3 gene, sits on the surface of the gut lining where it pulls riboflavin directly from our diet.

Although these transporters all bind riboflavin with great specificity, their distinct locations ensure that cells everywhere receive an adequate supply.

When a variant occurs in any of these three genes, the resulting transporter protein may be abnormal, inefficient or entirely absent. This defect prevents riboflavin from crossing cell membranes, so even if blood levels of vitamin B₂ appear normal, cells become starved of this vital nutrient.

Variants in the SLC52A2 and SLC52A3 genes cause RTD type 2 and type 3 respectively, while deletions (loses) or variants in the SLC52A1 gene cause the much rarer RTD type 1, often associated with placental transport problems.

Riboflavin transporter deficiency is considered as a neuronopathy, meaning a disorder of nerve cells, because it primarily damages motor neurons which carry signals from the brain or spinal cord to muscles, and sensory neurons, which relay sensations such as touch, pain and temperature back to the central nervous system. In RTD, the most vulnerable neurons are in the brainstem (including the pons and medulla oblongata, which connect the brain to the spinal cord) and in the spinal cord itself. As these nerve cells fail, affected people typically experience progressive hearing loss and difficulty controlling certain facial and throat muscles, leading to challenges with swallowing and speaking. Over time, weakness can spread to the arms, legs and even the muscles responsible for breathing.

In RTD type 1, infants who inherit only one variant in the SLC52A1 gene usually remain symptom-free. However, if a mother’s own riboflavin transport is impaired, her newborn may present at birth with unexplained high blood ammonia (hyperammonemia), metabolic acidosis (excess acidity in the bloodstream) or seizures. When there are variants in both copies of the SLC52A1 gene, children often develop seizures early on due to elevated ammonia levels. In contrast, people with RTD types 2 and 3 often present in childhood or adolescence with the characteristic nerve and muscle symptoms described above.

The SLC52A3 and the SLC52A2 gene variants that cause riboflavin transporter deficiency are inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

SLC52A1 gene variants follow autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.

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Affected populations

Riboflavin transporter deficiency is thought to affect females and males in equal numbers. The exact number of people who have this disorder is unknown. Rare disorders like riboflavin transporter deficiency often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. Researchers think that these disorders are underdiagnosed.

It is estimated that at least 1 in 1,000,000 people in the general population have riboflavin transporter deficiency.  As of 2025, about 325 cases have been reported in the medical literature worldwide. The organization Cure RTD has a  RTD Registry of people with this diagnosis. Between 2010 and 2024, there have been 392 people with genetically confirmed RTD in this registry including 205 people with RTD type 2 and 187 people with RTD type 3.

To date, only three cases of riboflavin transporter deficiency type 1 (RTD1) have been reported. The first was described in 2007, and four years later a newborn developed a temporary form of multiple acyl-CoA dehydrogenase deficiency (MADD) thought to be due to a small loss (microdeletion) in the mother’s SLC52A1 gene. In another family, both mother and infant carried different, single copy changes within the non-coding (intronic) regions of the SLC52A1 gene. The baby’s symptoms resolved completely once vitamin B₂ supplementation was started. More recently, in 2020, an infant was found to have a deletion in both copies of the SLC52A1 gene even though the mother showed no signs of RTD1 herself, leading to more severe symptoms.

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Disorders with Similar Symptoms

Symptoms of the following disorders can be similar to those of riboflavin transporter deficiency. Comparisons may be useful for a differential diagnosis.

Glutaric aciduria II, (also known as multiple acyl-CoA dehydrogenase deficiency, or MADD) is due to a defect that prevents the breakdown of multiple organic acids. As a result, affected neonates may present with a severe “neonatal” form that includes congenital anomalies and a high mortality rate, whereas those with the milder “late-onset” form can develop variable symptoms such as recurrent nausea, vomiting, lethargy, proximal muscle weakness and fasting hypoglycemia. Unlike riboflavin transporter deficiency, where serum vitamin B₂ may appear normal despite cellular deficiency, glutaric aciduria II is characterized by elevated levels of acyl-carnitines and organic acids in blood and urine, and responds to a combination of dietary management and, often, riboflavin as a cofactor adjunct rather than as primary therapy.

Several genetic nerve-cell disorders can also mimic the progressive muscle weakness of RTD but carry their own hallmarks. These may include:

• Spinal muscular atrophy with respiratory distress type I (SMARD1), where infants typically present very early with severe breathing muscle paralysis and marked muscle wasting
• Disorders historically compared to infantile-onset (juvenile) amyotrophic lateral sclerosis (ALS), Madras motor neuron disease and Nathalie syndrome, which all cause limb‐weakness but without the prominent hearing loss or swallowing problems seen in RTD
• Facial‐onset sensory‐motor neuronopathy which begins with numbness and tingling in the face
• Joubert syndrome which shows a characteristic “molar tooth” appearance on brain imaging
• Allgrove (or triple A) syndrome which combines dry eyes, difficulty swallowing and adrenal gland problems

In addition, immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or acute disseminated encephalomyelitis (ADEM) can present with weakness, sensory changes and even cranial nerve involvement that may be similar to RTD. These conditions trigger inflammation that damages the insulating sheath around nerves (myelin), which can be detected by elevated protein in the spinal fluid, nerve conduction studies and signs of inflammation on MRI. Genetic testing and vitamin B₂ uptake studies may be needed to make a definitive diagnosis.

By combining the clinical pattern, specialized blood and urine tests, imaging and genetic analysis, clinicians can distinguish RTD from these other disorders and begin the correct therapy as early as possible.

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Diagnosis

A diagnosis of riboflavin transporter deficiency begins when a doctor recognizes the combination of progressive hearing loss, muscle weakness, especially of the face, throat and limbs, and respiratory difficulties. A careful review of personal and family medical history, together with a comprehensive physical and neurological examination, helps to identify this pattern. Because the root problem in RTD is in cellular uptake of riboflavin rather than total dietary intake, routine blood tests may not reveal low vitamin B₂ levels. Genetic testing is therefore essential for a definitive diagnosis.

Newborn screening programs do not yet include riboflavin transporter deficiency, and definitive diagnosis depends on molecular genetic testing. This specialized analysis, performed at reference laboratories, looks for disease-causing variants in the SLC52A1, SLC52A2 or SLC52A3 genes, each of which encodes one of the three key riboflavin “carrier” proteins. Since early treatment with high-dose riboflavin (vitamin B₂) can prevent irreversible nerve damage, supplementation should begin as soon as the diagnosis is suspected, even before genetic testing results are completed. When started early, treatment can preserve hearing, maintain muscle strength and protect breathing function over the long term.

To identify the source of muscle weakness, an electromyogram (EMG) should be done. During an EMG, a very fine electrode is inserted into a muscle to record its electrical activity when at rest and during contraction; this helps distinguish whether weakness arises in the muscle fibers themselves or in the nerves that control them.

Complementary nerve conduction studies use surface electrodes to stimulate peripheral nerves, often in the arms and legs, and then measure how quickly electrical impulses travel. In riboflavin transporter deficiency, sensory nerve action potentials (SNAPs), which reflect the function of sensory fibers, are often undetectable, confirming that the problem lies in nerve function rather than muscle alone.

Because riboflavin transporter deficiency frequently involves the nerves of the brainstem and inner ear, tests of nerve signaling in these areas are also informative. A visual evoked potential (VEP) evaluates the brain’s electrical response to a flashing light, while brainstem auditory evoked response (BAER) testing measures the electrical signals traveling from the ear through the brainstem; abnormalities on these studies can help explain visual or hearing difficulties. Some doctors may order an electroencephalogram (EEG) to record the brain’s electrical activity and rule out seizure disorders, especially in infants who present with unexplained convulsions.

Advanced imaging is generally used to exclude other causes rather than to diagnose transporter deficiency itself. Magnetic resonance imaging (MRI) uses magnetic fields and radio waves to produce detailed pictures of the brain and spinal cord. In most people with riboflavin transporter deficiency, the MRI appears normal; in a minority, it may show atrophy (shrinkage) of the cerebellum, the part of the brain that coordinates movement. Blood tests to measure flavin levels or metabolites such as acylcarnitines can sometimes be abnormal, but they are neither sensitive nor specific enough to confirm the diagnosis on their own.

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Standard Therapies

Treatment

The main treatment is high-dose supplementation of riboflavin. Most affected people improve with this treatment. Some people improve rapidly while others improve gradually over 12 months. The optimum dose, best delivery method, or best frequency to take riboflavin supplementation are unknown and treatment needs to be individualized. Doctors will give riboflavin supplements gradually increasing amounts until an optimal dose is reached for each person and until blood tests show that riboflavin and its two key active forms (FMN, flavin mononucleotide, and FAD, flavin adenine dinucleotide, both of which help enzymes do their jobs) are in the normal range. In adults, this often means 2–3 grams of vitamin B₂ each day split into two to four smaller doses so that blood levels stay steady.

By flooding the bloodstream with riboflavin, even the few working transporters in the cell membrane, plus other ways that riboflavin can slip into cells without a transporter, can bring enough vitamin B₂ into cells to rebuild those critical FMN and FAD “helper molecules.” In RTD types 2 and 3, lifelong supplementation often stabilizes or even reverses hearing loss, muscle weakness and respiratory difficulties when started promptly. Many people notice improvements in hearing, muscle strength and breathing within days to weeks; others get better more slowly, over months or even up to a year. A small number may only improve modestly or may see symptoms return over time, which is why early diagnosis and finding the right dose are so important. According to how the people respond to treatment they may be classified in rapid, slow and non-responders.

Because a shortage of FMN and FAD also weakens the cell’s natural antioxidant defenses, the bodies’ way of neutralizing harmful “free radicals” (unstable molecules that can damage cell structures), doctors often add antioxidant medications:

• N-acetylcysteine: This builds up glutathione (the body’s main antioxidant) and has been shown, even in lab-grown nerve cells from affected people, to improve the tiny powerhouses in our cells (mitochondria), making them healthier and more efficient.
• Coenzyme Q₁₀ or idebenone: Both help the mitochondria’s “electron transport chain” (the process cells use to make energy) work better, and they mop up extra free radicals.
• EPI-743 (vatiquinone): A newer compound that crosses into the brain, turns on the Nrf2 antioxidant pathway (a master switch that boosts many antioxidant defenses), and raises glutathione levels more potently than simpler agents.
• Vitamins C and E: This is sometimes added for extra “free-radical protection,” often given alongside N-acetylcysteine to keep the overall “redox” (reduction–oxidation) balance in check.

Throughout treatment, doctors should do blood tests to monitor flavin levels (to make sure FMN and FAD are back in the normal range), acylcarnitine profiles (blood tests that show how well fatty acids are being processed) and clinical motor-function scales (standardized tests of strength and movement).

Other treatments of riboflavin transporter deficiency are symptomatic and supportive:

• If swallowing is weak, a temporary feeding tube makes sure nutrition stays adequate.
• Infants or children whose breathing muscles are too weak may need noninvasive ventilation (a mask that helps push air into the lungs) or, in severe cases, a tracheostomy (a small airway opening in the neck).
• Audiologists (hearing specialists) evaluate hearing loss and may recommend hearing aids or cochlear implants, which bypass damaged nerve pathways to send sound straight to the auditory nerve.
• For vision problems, low-vision aids (like magnifiers) and special education services help with reading and learning.
• Physical and occupational therapy preserve muscle tone and flexibility, prevent contractures (permanent tightening of muscles or tendons) and teach adaptive strategies; braces, orthotic devices, or wheelchairs can support mobility.
• Curvature of the spine (scoliosis) is managed by pediatric bone specialists, up to and including surgery if needed.

Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who specialize in diagnosing and treating disorders of brain and nervous system in children (pediatric neurologists), neurologists, physicians who specialize in diagnosing and treating disorders of the eye in children (pediatric ophthalmologists), ophthalmologists, physicians who specialize in diagnosing and treating disorders of the ears (audiologists) and other healthcare professionals may need to systematically and comprehensively plan treatment. Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.

Females who have riboflavin transporter deficiency and females who have one gene variant (carriers) for these disorders should receive riboflavin supplementation before and during pregnancy and when breast feeding.

For families affected by RTD, it is important to understand that riboflavin plays a vital role not only in energy production but also in maintaining the health of nerve cells. This highlights the value of genetic counseling, early monitoring, and timely treatment. With the right care, many serious complications can be prevented or reduced, helping people with RTD live healthier and more active lives.

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Clinical Trials and Studies

Looking forward, laboratory models like patient-derived stem cells, three-dimensional nerve-muscle “organoids,” gene therapy and gene-editing tools such as CRISPR-Cas9, offer hope for more targeted treatments

The Cure RTD Foundation maintains a registry for riboflavin transporter deficiency. A registry is a special database that contains information about individuals with a specific disorder or group of conditions. The collection of data about rare disorders may enable researchers to increase the understanding of such disorders, expand the search for treatments, and accelerate clinical trials into specific treatment options. For more information, visit: https://curertd.org/research/rtdregistry/.

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

JOURNAL ARTICLES
Mei C, Magliocca V, Chen X, et al. Riboflavin transporter deficiency: AAV9-SLC52A2 gene therapy as a new therapeutic strategy. Front Cell Neurosci. 2025;19:1523773. Published 2025 Mar 11. doi:10.3389/fncel.2025.1523773

Jaeger B, Hoytema van Konijnenburg E, Groenveld MA, Langeveld M, Wolf NI, Bosch AM. Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study. Orphanet J Rare Dis. 2024;19(1):410. Published 2024 Nov 1. doi:10.1186/s13023-024-03428-y

Magliocca V, Lanciotti A, Ambrosini E, et al. Modeling riboflavin transporter deficiency type 2: from iPSC-derived motoneurons to iPSC-derived astrocytes. Front Cell Neurosci. 2024;18:1440555. Published 2024 Jul 24. doi:10.3389/fncel.2024.1440555

Fennessy JR, Cornett KMD, Burns J, Menezes MP. Benefit of high-dose oral riboflavin therapy in riboflavin transporter deficiency. J Peripher Nerv Syst. 2023;28(3):308-316. doi:10.1111/jns.12587

Colasuonno F, Marioli C, Tartaglia M, Bertini E, Compagnucci C, Moreno S. New Insights into the Neurodegeneration Mechanisms Underlying Riboflavin Transporter Deficiency (RTD): Involvement of Energy Dysmetabolism and Cytoskeletal Derangement. Biomedicines. 2022;10(6):1329. Published 2022 Jun 6. doi:10.3390/biomedicines10061329

Kang U, Yang DH, Nam SO, et al. Riboflavin Transporter 1 Deficiency Caused by a Homozygous Single Exonal Deletion of SLC52A1. Ann Child Neurol. 2020;28(4):160-163.

Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, Olsen RKJ. Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism. Int J Mol Sci. 2020;21(11):3847. Published 2020 May 28. doi:10.3390/ijms21113847

Anderson P, Schaefer S, Henderson L, Bruce IA. Cochlear implantation in children with auditory neuropathy: Lessons from Brown-Vialetto-Van Laere syndrome. Cochlear Implants Int. 2019;20(1):31-38. doi:10.1080/14670100.2018.1534035 https://www.ncbi.nlm.nih.gov/pubmed/30332915

Woodcock IR, Menezes MP, Coleman L, et al. Genetic, radiologic, and clinical variability in Brown-Vialetto-van Laere syndrome. Semin Pediatr Neurol. 2018;26:2-9. https://www.ncbi.nlm.nih.gov/pubmed/29961509

Allison T, Roncero I, Forsyth R, Coffman K, Pichon JL. Brown-Vialetto-Van Laere syndrome as a mimic of neuroimmune disorders: 3 cases from the clinic and review of the literature. J Child Neurol. 2017;32:528-532. https://www.ncbi.nlm.nih.gov/pubmed/28116953

Jaeger B, Bosch AM. Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience. J Inherit Metab Dis. 2016;39:559-564. a

Schiff M, Veauville-Merllie A, Su CH, et al. SLC25A32 mutations and riboflavin-responsive exercise intolerance. N Engl J Med. 2016;374:795-797. https://www.ncbi.nlm.nih.gov/pubmed/26933868

Menezes MP, O’Brien K, Hill M, et al. Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency. Dev Med Child Neurol. 2016;58:848-854. https://www.ncbi.nlm.nih.gov/pubmed/26918385

Menezes MP, Farrar MA, Webster R, et al. Pathophysiology of motor dysfunction in a childhood motor neuron disease caused by mutations in the riboflavin transporter. Clin Neurophysiol. 2016;127:911-918. https://www.ncbi.nlm.nih.gov/pubmed/26092362

Foley AR, Menezes MP, Pandraud A, et al. Treatable childhood neuropathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014;137:44-56. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891447/

Nalini A, Pandraud D, Mok K, Houlden H. Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome. J Neurol Sci. 2013 Nov 15;334(1-2):119-22. doi: 10.1016/j.jns.2013.08.003. Epub 2013 Aug 13. https://www.ncbi.nlm.nih.gov/pubmed/24139842

Bosch AM, Stroek K, Abeling NG, et al. The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives. Orphanet J Rare Dis. 2012;7:83. https://www.ncbi.nlm.nih.gov/pubmed/23107375

Haack TB, Makowski C, Yao Y, et al. Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome. J Inherit Metab Dis. 2012;35:943-948. https://www.ncbi.nlm.nih.gov/pubmed/22864630

Bosch AM, Abeling NG, Ijist L, et al. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. J Inherit Metab Dis. 2011;34:159-164. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026695/

Ho G, Yonezawa A, Masuda S, et al. Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B. Hum Mutat. 2011;32:E1976–84. https://www.ncbi.nlm.nih.gov/pubmed/21089064

Yao Y, Yonezawa A, Yoshimatsu H, et al. Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. J Nutr. 2010;140(7):1220–1226. doi: 10.3945/jn.110.122911. https://www.ncbi.nlm.nih.gov/pubmed/20463145

Van Laere J. Paralysie bulbo-pontine chronique progressive familiale avec surdité. Un cas de syndrome de Klippel-Trenaunay dans la même fratrie – problèmes diagnostiques et génétiques. Rev Neurol. 1966;115:289–295.

Vialetto E. Contributo alla forma ereditaria della paralisi bulbare progressive. Riv Sper Freniat. 1936;40:1–24.

Brown CH. Infantile amyotrophic lateral sclerosis of the family type. J Nerv Ment Dis. 1894;21:707–716.

INTERNET

Cali E, Dominik N, Manole A, et al. Riboflavin Transporter Deficiency. 2015 Jun 11 [Updated 2021 Apr 8]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK299312/ Accessed July 22, 2025.

Riboflavin transporter deficiency. Orphanet. February 2020. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=97229 Accessed July 22, 2025.

National Institutes of Health Office of Dietary Supplements. Riboflavin. Updated May 11, 2022. Available at: https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/ Accessed July 22, 2025.

Cure RTD Foundation. About Riboflavin Transporter Deficiency. Available at: https://curertd.org/what-is-rtd/aboutrtd/ Accessed July 22, 2025.

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Programs & Resources

• Assistance Programs
• Patient Organizations
• More Information

RareCare^® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Learn more about Patient Assistance Programs >

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