Riboflavin transport deficiency (RTD) is a genetic, neurodegenerative condition that affects the transport of riboflavin. Riboflavin, also known as vitamin B2, is a water-soluble vitamin. It is important for energy production and has antioxidant properties essential for the immune system, skin and hair health.¹ Riboflavin can only be obtained through diet and can be found in many types of food such as dairy products, meat, fish, grain and green vegetables.  

In the body, riboflavin is transported into cells through three types of riboflavin transporters that are found in different parts of the body.² Riboflavin is then converted into molecules called flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). They are important for the breakdown of carbohydrate, fat and protein to produce energy, and for the maintenance of nerve cells.^2,3

Riboflavin transport deficiency (RTD) is caused by genetic changes in the genes that produce these riboflavin transporters.³ In RTD, these riboflavin transporters do not work properly and there is not enough riboflavin in cells, leading to nerve damage, particularly affecting muscles, movement and the senses. 

There are three different types of RTD depending on the gene that is affected: 

• Riboflavin transport deficiency type 1/RTD type 1 – involves the SLC52A1 gene. In some cases, the affected SLC52A1 gene in the mother results in symptoms in the newborn (also known as maternal riboflavin deficiency). RTD type 1 has been reported in a small number of cases in medical literature.

• Riboflavin transport deficiency type 2/RTD type 2 – involves the SLC52A2 gene 

• Riboflavin transport deficiency type 3/RTD type 3 – involves the SLC52A3 gene 

Synonyms for RTD: Brown-Vialetto-van Laere syndrome, Fazio-Londe syndrome, riboflavin transporter deficiency neuronopathy, sensorineural hearing loss-pontobulbar palsy syndrome.^3,5,6

RTD was previously referred to as Brown-Vialetto-Van Laere syndrome or Fazio-Londe syndrome, depending on the symptoms. They have been since recognised to be caused by defects in riboflavin transporters and renamed as RTD.³

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:97229 Riboflavin transporter deficiency

• ORPHA:411712 Maternal riboflavin deficiency
• ORPHA:572543 RFVT2-related riboflavin transporter deficiency
• ORPHA:572550 RFVT3-related riboflavin transporter deficiency

ICD-11: LD2H.Y Other specified syndromic genetic deafness

Symptoms of RTD are caused by nerve damage and vary between individuals.³ Symptoms usually begin in babies or early childhood, but can sometimes present only during adulthood.⁴ In babies, breathing difficulties often appear first and may be life-threatening if left untreated.⁵

Other common signs and symptoms of RTD include:^4,7

• hearing loss which often worsen over time
• muscle weakness especially in the upper limbs, face, neck and trunk (central part of the body)
• breathing problems due to weakness of the diaphragm (main muscle for breathing)
• problem with coordination (ataxia), balance and movement due to loss of sensory feedback signals of the body’s position and movement
• vision loss and abnormal eye movements due to damage of optic nerves
• difficulty speaking and swallowing due to weakness of the tongue and throat muscles

RTD type 1 has been reported in a small number of individuals in medical literature, and their symptoms may differ than described above. In babies with RTD type 1, symptoms include high blood ammonia, metabolic acidosis (excess acidity in the bloodstream) or seizures – which resembles another condition known as multiple acyl-CoA dehydrogenase deficiency.^5,9

Please speak to your medical team to learn more about the symptoms and health implications of RTD.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

RTD is a genetic condition. It is caused by disease-causing genetic changes (variants) in certain genes that produce riboflavin transporters.³ The different types of RTD involve different genes:

• RTD type 1 – involves the SLC52A1 gene that produces riboflavin transporter 1/RFVT1. RFVT1 is mainly found in placenta (where it transports riboflavin from the mother to the baby), and in the baby’s developing gut.
• RTD type 2 – involves the SLC52A2 gene that produces riboflavin transporter 2/RFVT2. RFVT2 is found in many tissues of the body, with high levels in the brain and spinal cord.
• RTD type 3 – involves the SLC52A3 gene that produces riboflavin transporter 3/RFVT3. RFVT3 is found in the small intestine where it is involved in absorbing the riboflavin from food.⁸

RTD can be passed down from parents to children. Everyone has two copies of each gene, one from their mother and one from their father. RTD type 1 is an autosomal dominant condition, which means that having a genetic variant in just one of the SLC52A1 gene copies can result in the condition.^3,9 In some cases, newborns with RTD type 1 do not carry any genetic variant in their own SLC52A1 gene. However, their mother may have the variant, which results in inadequate riboflavin transport during pregnancy, and consequently causes the symptoms observed in affected babies.⁹

RTD type 2 and RTD type 3 are both autosomal recessive conditions, which means that genetic variants in both copies of SLC52A2 or SLC52A3 genes are necessary to cause the condition.

More information on the inheritance patterns can be found at:

• Centre for Genetics Education: Autosomal dominant inheritance
• Centre for Genetics Education: Autosomal recessive inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of RTD may be made based on:^3,4,7

• physical examination
• family history
• hearing tests
• neurological tests to check the activity and health of the nervous system
• electromyography (EMG) to check the health of muscles and nerves that control the muscles
• brain and spinal cord imaging (MRI scans)
• blood tests to measure riboflavin levels
• genetic testing to look for variants in the SLC52A1, SLC52A2 or SLC52A3 gene

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms, such as congenital or mitochondrial myopathy, rapid progressive neuropathies, Guillain-Barre syndrome, amyopathic lateral sclerosis, multiple acyl-CoA dehydrogenase deficiency, spinal muscular atrophy, achalasia-addisonianism-alacrimia syndrome and hereditary motor neuropathy.^4,6,7

Please speak to your medical team to learn more about the available diagnostic pathways for RTD.

There is currently no curative treatment for RTD. Treatment for most people with RTD involves oral supplementation of riboflavin.⁴ The dose of riboflavin supplementation varies depending on the severity of the condition and the response of the individual to the treatment. Early initiation of riboflavin supplements may prevent nerve damage, stabilise or improve symptoms in most individuals.^3,4,6

Other treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. This may include hearing aid such as cochlear implants, respiratory support to help breathing, mobility aids, physiotherapy, occupational therapy, orthotics, speech and language therapy, and vision aids.^3,6

Individuals may be monitored for their hearing, vision, respiratory function, scoliosis, and managed accordingly.⁷ More information about surveillance recommendation for RTD can be found at Long‐term outcomes in children with riboflavin transporter deficiency and surveillance recommendations.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of people living with RTD may include general practitioners (GP), paediatricians, audiologists, ENT specialists, neurologists, ophthalmologists, occupational therapists, physiotherapists, speech pathologists, genetic counsellors and others.^3,7 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. Palliative care is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. For more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

Healthcare professionals involved in the care of people living with RTD may include general practitioners (GP), paediatricians, audiologists, ENT specialists, neurologists, ophthalmologists, occupational therapists, physiotherapists, speech pathologists, genetic counsellors and others.^3,7 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any clinical care guidelines for RTD in Australia or internationally. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following resources include clinical management for health professionals:

Long‐term outcomes in children with riboflavin transporter deficiency and surveillance recommendations includes recommendations for tracking disease progression and response to riboflavin supplementation over time; based on long-term outcome data from a study performed at the Children’s Hospital at Westmead, NSW; published in 2024.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Australian Organisation:
We are not aware of any rare disease organisations for RTD in Australia. If you are aware of any relevant Australian organisations, please let us know via the Contribute page.

International Organisation:
Cure RTD Foundation (United States of America)
Website: https://curertd.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

RTD varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information relevant to RTD and riboflavin can be found at:

• healthdirect: Vitamin B and your health
• Better Health Channel: Vitamin B
• Eat for Health: Riboflavin Nutrient Reference Values for Australia and New Zealand
• Genetic and Rare Diseases (GARD) Information Center: Riboflavin transporter deficiency
• National Organization for Rare Disorders (NORD): Riboflavin Transporter Deficiency

GeneReviews®: Riboflavin Transporter Deficiency
Online Mendelian Inheritance in Man, OMIM^®:#614707 Brown-Vialetto-Van Laere Syndrome 2; BVVLS2
Online Mendelian Inheritance in Man, OMIM^®:#211599 Fazio-Londe disease
Online Mendelian Inheritance in Man, OMIM®:#615026 Riboflavin deficiency; RBFVD
Orphanet: Riboflavin transporter deficiency
Orphanet: Maternal riboflavin deficiency
Orphanet: Riboflavin transporter deficiency type 2
Orphanet: Riboflavin transporter deficiency type 3
Human Phenotype Ontology (HPO): Riboflavin transporter deficiency
Inborn Errors of Metabolism Knowledgebase (IEMbase): Riboflavin transporter 1 deficiency
Inborn Errors of Metabolism Knowledgebase (IEMbase): Riboflavin transporter 2 deficiency
Inborn Errors of Metabolism Knowledgebase (IEMbase): Riboflavin transporter 3 deficiency

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. 

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.