Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience.

Bregje Jaeger,Annet M Bosch

doi:10.1007/s10545-016-9924-2

Abstract

IntroductionRiboflavin (vitamin B2) is absorbed in the small intestine by the human riboflavin transporters RFVT1 and RFVT3. A third riboflavin transporter (RFVT2) is expressed in the brain. In 2010 it was demonstrated that mutations in the riboflavin transporter genes SLC52A2 (coding for RFVT2) and SLC52A3 (coding for RFVT3) cause a neurodegenerative disorder formerly known as Brown-Vialetto-Van Laere (BVVL) syndrome, now renamed to riboflavin transporter deficiency. Five years after the diagnosis of the first patient we performed a review of the literature to study the presentation, treatment and outcome of patients with a molecularly confirmed diagnosis of a riboflavin transporter deficiency.MethodA search was performed in Medline, Pubmed using the search terms ‘Brown-Vialetto-Van Laere syndrome’ and ‘riboflavin transporter’ and articles were screened for case reports of patients with a molecular diagnosis of a riboflavin transporter deficiency.ResultsReports on a total of 70 patients with a molecular diagnosis of a RFVT2 or RTVT3 deficiency were retrieved. The riboflavin transporter deficiencies present with weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a sensorimotor axonal neuropathy and cranial neuropathy. Biochemical abnormalities may be absent and the diagnosis can only be made or rejected by molecular analysis of all genes. Treatment with oral supplementation of riboflavin is lifesaving. Therefore, if a riboflavin transporter deficiency is suspected, treatment must be started immediately without first awaiting the results of molecular diagnostics.

Highlights

Riboflavin is absorbed in the small intestine by the human riboflavin transporters RFVT1 and RFVT3
The riboflavin transporter deficiencies present with weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a sensorimotor axonal neuropathy and cranial neuropathy
Riboflavin (7,8-dimethyl-10-ribityl-isoalloxazine, vitamin B2) is a water soluble vitamin which is the precursor of the active coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), important cofactors for carbohydrate, amino acid and lipid metabolism (Lienhart et al 2013)

Summary

Introduction

Riboflavin (vitamin B2) is absorbed in the small intestine by the human riboflavin transporters RFVT1 and RFVT3. In 2010 it was demonstrated that mutations in the riboflavin transporter genes SLC52A2 (coding for RFVT2) and SLC52A3 (coding for RFVT3) cause a neurodegenerative disorder formerly known as Brown-Vialetto-Van Laere (BVVL) syndrome, renamed to riboflavin transporter deficiency. Method A search was performed in Medline, Pubmed using the search terms ‘Brown-Vialetto-Van Laere syndrome’ and ‘riboflavin transporter’ and articles were screened for case reports of patients with a molecular diagnosis of a riboflavin transporter deficiency. Riboflavin is a well-known chaperone effective in the treatment of inborn errors of metabolism such as MADD and mitochondrial disorders (Cornelius et al 2012; Carrozzo et al 2014). Three riboflavin transporters have been characterized: RFVT1 mostly expressed in small intestine, RFVT 2 mostly expressed in the brain and RFVT 3 mostly expressed in the small intestine (Fig. 1, adapted from Yonazawa 2013) (Yonezawa et al 2008; Yamamoto et al 2009; Yao et al 2010)

Results

Discussion

Conclusion