Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency

Dev Med Child Neurol. 2016 Aug;58(8):848-54. doi: 10.1111/dmcn.13084. Epub 2016 Feb 25.


Aim: Mutations in the genes encoding the riboflavin transporters RFVT2 and RFVT3 have been identified in Brown-Vialetto-Van Laere syndrome, a neurodegenerative disorder characterized by hearing loss and pontobulbar palsy. Treatment with riboflavin has been shown to benefit individuals with the phenotype of RFVT2 deficiency. Understanding the characteristics of hearing loss in riboflavin transporter deficiency would enable early diagnosis and therapy.

Method: We performed hearing assessments in seven children (from four families) with RFVT2 deficiency and reviewed results from previous assessments. Assessments were repeated after 12 months and 24 months of riboflavin therapy and after cochlear implantation in one individual.

Results: Hearing loss in these individuals was due to auditory neuropathy spectrum disorder (ANSD). Hearing loss was identified between 3 years and 8 years of age and progressed rapidly. Hearing aids were not beneficial. Riboflavin therapy resulted in improvement of hearing thresholds during the first year of treatment in those with recent-onset hearing loss. Cochlear implantation resulted in a significant improvement in speech perception in one individual.

Interpretation: Riboflavin transporter deficiency should be considered in all children presenting with an auditory neuropathy. Speech perception in children with ANSD due to RFVT2 deficiency may be significantly improved by cochlear implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Age of Onset
  • Audiometry
  • Bulbar Palsy, Progressive / complications*
  • Bulbar Palsy, Progressive / etiology*
  • Bulbar Palsy, Progressive / genetics
  • Child
  • Child, Preschool
  • Cochlear Implantation / methods
  • Electroencephalography
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / genetics
  • Female
  • Follow-Up Studies
  • Hearing Loss, Central / complications*
  • Hearing Loss, Central / drug therapy
  • Hearing Loss, Central / surgery
  • Hearing Loss, Sensorineural / complications*
  • Hearing Loss, Sensorineural / etiology*
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Male
  • Membrane Transport Proteins / deficiency*
  • Membrane Transport Proteins / genetics
  • Mutation / genetics
  • Otoacoustic Emissions, Spontaneous / drug effects
  • Otoacoustic Emissions, Spontaneous / genetics
  • Riboflavin / therapeutic use
  • Riboflavin Deficiency / complications*
  • Riboflavin Deficiency / drug therapy
  • Speech Perception / drug effects
  • Speech Perception / genetics


  • Membrane Transport Proteins
  • SLC52A3 protein, human
  • Riboflavin

Supplementary concepts

  • Auditory neuropathy
  • Brown-Vialetto-Van Laere syndrome