Benefit of high‐dose oral riboflavin therapy in riboflavin transporter deficiency

Abstract

Background and AimsRiboflavin Transporter Deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation has been shown to be beneficial in short‐term reports but the quantum of benefit in various clinical domains is not well understood.MethodsA PubMed search was conducted which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow‐up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed.ResultsSeventy‐six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%), and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy‐dependent.InterpretationRiboflavin supplementation is a life‐saving intervention for patients with RTD and results in profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease modifying therapies.This article is protected by copyright. All rights reserved.

A riboflavin transporter deficiency presenting as pure red cell aplasia: a pediatric case report

“…RTDs have a low incidence rate and significant clinical heterogeneity. Patients often present with neurological symptoms or deafness, and approximately 70% of individuals have an abnormal acylcarnitine profile before riboflavin supplementation ( 10 ). Due to impaired iron absorption resulting from riboflavin deficiency, some patients may experience mild-to-moderate decreases in RBC counts and/or Hb levels.…”

Phenotypic Variability Related to Mutations in Riboflavin Transporter in Brazilian Children: Pediatric Case Series

“…It serves as an integral component of flavoenzymes, namely flavin mononucleotide and flavin adenine dinucleotide molecules, and functions as a coenzyme essential for the metabolism of amino acids, carbohydrates, and lipids, particularly in neurons. 1 6 7 8 RFVTs are transmembrane proteins that mediate cellular uptake of riboflavin and are crucial for delivering dietary riboflavin to target tissues. 9 10 11 The RFVT3 transporter, encoded by SLC52A3 , plays a primary role in the small intestine, while the RFVT2 transporter, encoded by SLC52A2 , is predominant in the brain and spinal cord.…”

“…9 10 11 The RFVT3 transporter, encoded by SLC52A3 , plays a primary role in the small intestine, while the RFVT2 transporter, encoded by SLC52A2 , is predominant in the brain and spinal cord. 7 8 12 13 Mutations in SLC52A2 and SLC52A3 reduce RFVT protein expression, thereby diminishing riboflavin uptake. 8 While uncertain, it is hypothesized that cellular energy dysmetabolism, with redox imbalance, involving mitochondrial and peroxisomal dysfunction, and cytoskeletal derangement in neurons contribute to a specific pattern of neuronal dysfunction in BVVL.…”

“…7 8 12 13 Mutations in SLC52A2 and SLC52A3 reduce RFVT protein expression, thereby diminishing riboflavin uptake. 8 While uncertain, it is hypothesized that cellular energy dysmetabolism, with redox imbalance, involving mitochondrial and peroxisomal dysfunction, and cytoskeletal derangement in neurons contribute to a specific pattern of neuronal dysfunction in BVVL. 8 14…”