Review of Riboflavin Transporter Deficiency Syndrome: Sameness in Genotype occurs with Variations in Phenotype.

Abstract

Riboflavin Transporter Deficiency Syndrome (RTD) is a rare childhood neurodegenerative disorder. RTD is acquired as an autosomal recessive pattern, which indicates that a child whose parents are carriers of RTD has a 25% chance of having the disease [homozygous for the RTD trait], a 50% chance of being a carrier [a heterozygous for the RTD trait], and a 25% chance of not having the disease [homozygous negative for the RTD trait]. RTD is a sensory motor neuron disease with symptoms such as auditory neuropathy, sensory ataxia, sensorineural deafness, and muscle weakness. These symptoms were first described in 1892 but diagnosis only became established in 2009 following the application of molecular biology investigation to discern the cause. Through exome sequencing and genetic testing, a mutation of the Solute Carrier 52A gene (SLC52A) was found to be implicated in RTD. There is no cure for RTD currently, but dietary Riboflavin supplementation has been shown to be a very effective treatment for most RTD patients. The current treatment is based on mg Riboflavin/kg of Body Weight/day. This approach fails to consider the role of other potential factors in the efficacy of the therapy, as well as in the variations and severity of the symptoms. This research uses case reports and meta‐analysis of available work reports to highlight the potential pathophysiological factors that may contribute to the variations, severity of signs and symptoms reported, and treatment responses in RTD affected patients. This report includes the molecular, cellular, and the phenotypic dynamics of RTD, and ends with a review of reported treatment responses. It is believed that such a hierarchical assessment will better equip the patients, their families, and the attending clinicians with the knowledge to assess and treat each RTD patient individually and with greater accuracy, success and outcomes than in the past.Support or Funding InformationThis research supported by Institutional Resources of the University of Science Arts and Technology, Montserrat, British West Indies and the Einstein Institute, USA.