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Disease Profile

Riboflavin transporter deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

G12.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pontobulbar palsy and neurosensory deafness; BVVLS; Pontobulbar palsy with deafness;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Nervous System Diseases

Summary

Riboflavin transporter deficiency is a progressive neurodegenerative disease characterized by paralysis of the cranial nerves, sensorineural deafness, and signs of damage to other nerves. Symptoms may begin from infancy to early adulthood and worsen over time.[1][2] When the condition begins in infancy, the first symptom often is breathing problems, which can be life-threatening. When it begins in childhood or early adulthood, sensorineural deafness is usually the first symptom.[3] Other signs and symptoms may include vocal cord paralysis, droopy eyelids, facial weakness, slurred speech, difficulty swallowing, visual problems, autonomic dysfunction, breathing difficulties, and weakness of the neck, shoulder, and limbs.[1][2]

Riboflavin transporter deficiency may be caused by mutations in the SLC52A2 or SLC52A3 genes. Inheritance is autosomal recessive.[3] Treatment with riboflavin therapy has been used since 2010 and appears to be effective and possibly life-saving. Without treatment, affected infants typically survive less than one year.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Bulbar palsy
0001283
Progressive hearing impairment
0001730
30%-79% of people have these symptoms
Abnormality of eye movement
Abnormal eye movement
Abnormal eye movements
Eye movement abnormalities
Eye movement issue

[ more ]

0000496
Dysarthria
Difficulty articulating speech
0001260
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Facial palsy
Bell's palsy
0010628
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Limb muscle weakness
Limb weakness
0003690
Muscular hypotonia
Low or weak muscle tone
0001252
Myoclonus
0001336
Ptosis
Drooping upper eyelid
0000508
Respiratory insufficiency
Respiratory impairment
0002093
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
5%-29% of people have these symptoms
Abnormal autonomic nervous system physiology
0012332
Abnormality of macular pigmentation
0008002
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Ataxia
0001251
Cachexia
Wasting syndrome
0004326
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Color vision defect
Abnormal color vision
Abnormality of color vision

[ more ]

0000551
Diabetes insipidus
0000873
Gynecomastia
Enlarged male breast
0000771
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hypertension
0000822
Hypogonadism
Decreased activity of gonads
0000135
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Iris hypopigmentation
Light eye color
0007730
Optic disc pallor
0000543
Seizure
0001250
Sleep apnea
Pauses in breathing while sleeping
0010535
Tremor
0001337
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Percent of people who have these symptoms is not available through HPO
Abnormal cerebellum morphology
Abnormality of the cerebellum
Cerebellar abnormalities
Cerebellar abnormality
Cerebellar anomaly

[ more ]

0001317
Ankle clonus
Abnormal rhythmic movements of ankle
0011448
Autosomal recessive inheritance
0000007
Clumsiness
0002312
Cranial nerve motor loss
0007097
Diaphragmatic weakness
Weak diaphragm
0009113
External ophthalmoplegia
Paralysis or weakness of muscles within or surrounding outer part of eye
0000544
Hand muscle atrophy
Hand muscle degeneration
0009130
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Knee clonus
0011449
Kyphosis
Hunched back
Round back

[ more ]

0002808
Myopathic facies
0002058
Neck muscle weakness
Floppy neck
0000467
Nocturnal hypoventilation
0002877
Peripheral neuropathy
0009830
Progressive
Worsens with time
0003676
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Scoliosis
0002650
Sensorineural hearing impairment
0000407
Stridor
0010307
Tongue atrophy
Wasting of the tongue
0012473
Tongue fasciculations
Tongue twitching
Twitching of the tongue

[ more ]

0001308
Vocal cord paralysis
Inability to move vocal cords
0001605
Weak voice
Soft voice
0001621

Cause

Riboflavin transporter deficiency is caused by mutations in the SLC52A2 gene or the SLC52A3 gene. Some authors have proposed a classification system of types of riboflavin transporter deficiency depending on the underlying genetic cause, with those having a mutation in the SLC52A2 gene classified as type 2 and those having a mutation in the SLC52A3 gene classified as type 3.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment with riboflavin therapy (high-dose supplementation of riboflavin) has been used since 2010 and appears to be effective and possibly life-saving. Therefore, treatment should begin as soon as a riboflavin transporter deficiency is suspected, and should continue unless the diagnosis is ruled out with genetic testing.[1] Improvement of symptoms may occur within days to months after starting treatment, and starting treatment early appears to be associated with better and more rapid improvement.[4]

    More detailed information about this treatment and supportive care is available here on the GeneReviews website.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Riboflavin transporter deficiency. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Riboflavin transporter deficiency. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

          • The Orphanet Journal of Rare Diseases has published an article with information on this condition. This journal is affiliated with the Orphanet reference portal for information on rare diseases and orphan drugs.

            References

            1. Manole A and H Houlden. Riboflavin Transporter Deficiency Neuronopathy. GeneReviews. 06/11/2015; https://www.ncbi.nlm.nih.gov/books/NBK299312/.
            2. About BVVL. BVVL International. 2016; https://www.bvvlinternational.org/about-bvvl.html.
            3. Riboflavin transporter deficiency neuronopathy. Genetics Home Reference. January, 2016; https://ghr.nlm.nih.gov/condition/riboflavin-transporter-deficiency-neuronopathy.
            4. Jaeger B, Bosch AM. Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience. J Inherit Metab Dis. July, 2016; 39(4):559-564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920840/.
            5. Deficiencia del transportador de riboflavina. Orphanet. May 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=ES&Expert=97229.

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