Does riboflavin depletion cause auditory neuropathy spectrum disorder in at risk neonates?

We present a new hypothesis for the pathogenesis of auditory neuropathy spectrum disorder (ANSD) in at risk neonates involving depletion of riboflavin. The association between neonatal hyperbilirubinemia and ANSD is well recognized, yet causation has not been proven. The risk of ANSD does not correlate clearly with severity of hyperbilirubinemia and ASND only occurs in a small proportion of hyperbilirubinemic neonates. Additional, perhaps co-dependent, factors are therefore likely to be involved in pathogenesis. The metabolism of bilirubin consumes riboflavin and levels of riboflavin are depleted further by phototherapy. The neonate may also be deficient in riboflavin secondary to maternal deficiency, and reduced intake or impaired absorption. We propose that riboflavin depletion may be a significant contributor to development of ANSD in at risk neonates. The basis of this hypothesis is the recent recognition that impairment of riboflavin metabolism caused by genetic mutations (SLC52A2 or AIMF1) also causes ANSD.