Acknowledgement of Brown-Vialetto-Van Laere Syndrome has not been added yet.

BVVLS is extremely rare, with fewer than 100 cases reported in the medical literature. The exact prevalence is unknown. It affects both males and females and has been reported in various ethnic groups worldwide.

 

Name	Abbreviation
Riboflavin Transporter Deficiency	RTD
Fazio-Londe Syndrome

BVVLS is caused by mutations in either the SLC52A2 or the SLC52A3 genes, which encode riboflavin transporters (RFVT2 and RFVT3, respectively). These transporters are crucial for the uptake and utilization of riboflavin (vitamin B2), an essential nutrient for cellular energy production and metabolism. Riboflavin and flavin are important building blocks for other biological materials within the cell, which carry out a variety of functions that keep the cell healthy and running. Mutations in these genes result in reduced or absent function of the riboflavin transporters, leading to riboflavin deficiency at the cellular level. This deficiency impairs mitochondrial function and affects the nervous system, particularly the cranial nerves, causing them to be broken down. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the syndrome (see RareShare Guide on Genetic Inheritance).

 

The symptoms of BVVLS are primarily neurological and vary in severity:

• Hearing Loss: Progressive sensorineural hearing loss is one of the earliest and most common symptoms, often leading to deafness.

• Cranial Nerve Palsies: Multiple cranial nerve palsies result in facial weakness, difficulty swallowing (dysphagia), hoarseness, and vision problems such as double vision or ptosis (drooping eyelids).

• Bulbar Palsy: Bulbar palsy, involving the muscles responsible for speech, swallowing, and other functions, leads to slurred speech, difficulty eating, and aspiration risk.

• Respiratory Issues: Respiratory muscle weakness may develop, leading to breathing difficulties and the potential need for ventilatory support.

• Motor Weakness: Progressive weakness in the limbs and ataxia (loss of coordination) may occur, particularly as the disease progresses.

Diagnosis of BVVLS is based on the clinical presentation of symptoms, particularly the combination of hearing loss and cranial nerve palsies, and is confirmed by genetic testing. The rarity of the condition and its overlapping symptoms with other neurological disorders can make diagnosis challenging.

 

• Genetic Testing: Sequencing of the SLC52A2 and SLC52A3 genes is the definitive test to confirm BVVLS by identifying mutations.

• Electromyography (EMG) and Nerve Conduction Studies: These tests can assess the function of the cranial nerves and the extent of nerve damage.

• MRI and Other Imaging: Imaging studies may be used to rule out other causes of neurological symptoms and to assess the structure of the brain and cranial nerves.

• Audiometric Tests: Hearing tests are performed to evaluate the extent of sensorineural hearing loss.

Treatment for BVVLS focuses on managing symptoms and, most importantly, supplementing riboflavin to address the underlying deficiency:

• Riboflavin Supplementation: High-dose riboflavin (vitamin B2) supplementation is the mainstay of treatment. Early and continuous supplementation can stabilize or even improve symptoms, particularly if started before significant neurological damage occurs.

• Supportive Therapies: Physical therapy, speech therapy, and occupational therapy can help manage motor symptoms, speech difficulties, and improve quality of life.

• Hearing Aids and Cochlear Implants: For hearing loss, hearing aids or cochlear implants may be considered to improve hearing function.

• Respiratory Support: In cases of respiratory muscle weakness, non-invasive ventilation or other respiratory support may be necessary.

The prognosis for individuals with BVVLS varies widely depending on the timing of diagnosis and the initiation of riboflavin supplementation. Early diagnosis and treatment can significantly improve outcomes, potentially stabilizing symptoms and preventing further neurological damage. However, if untreated or diagnosed late, BVVLS can lead to severe disability and life-threatening complications, particularly from respiratory involvement. With appropriate management, some individuals may experience a significant reduction in symptom progression and an improved quality of life.

 

Tips or Suggestions of Brown-Vialetto-Van Laere Syndrome has not been added yet.

1. Bosch, A. M., Stroek, K., Abeling, N. G., et al. (2011). "The Brown-Vialetto-Van Laere and Fazio-Londe syndrome revisited: Natural history, treatment, and guidelines for diagnosis and management." Orphanet Journal of Rare Diseases, 6, 83.

2. Green, P., Wiseman, M., Crow, Y. J., et al. (2010). "Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54." The American Journal of Human Genetics, 86(3), 485-489.

3. Yamashita, S., Matsushima, K., Ohkubo, S., et al. (2017). "Riboflavin transporter deficiency and treatment." Journal of Human Genetics, 62(8), 757-762.

4. O'Callaghan, B., Bosch, A. M., & Houlden, H. (2019). "Riboflavin transporter deficiency: A review of the clinical presentation, diagnosis, and treatment of Brown-Vialetto-Van Laere syndrome, Fazio-Londe disease, and hereditary motor neuropathy type VI." Journal of Neurology, Neurosurgery & Psychiatry, 90(1), 4-11.

5. Johnson, J. O., Gibbs, J. R., Megarbane, A., et al. (2012). "Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease." Brain, 135(Pt 9), 2875-2882.