Riboflavin Transporter 1 Deficiency Caused by a Homozygous Single Exonal Deletion of SLC52A1

Abstract

Riboflavin (vitamin B2) is the solitary precursor for the biologically active cofactors known as the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) molecules [1]. These cofactors are required in oxidation-reduction (redox) reactions and act as cofactors for the electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH) [2]. The ETF and ETF-DH form electron transport pathways for at least 12 mitochondrial flavoprotein dehydrogenases involved in amino acid, fatty acid, and choline metabolism [3]. Variations of the ETF or ETF-DH cause multiple acyl-CoA dehydrogenation deficiencies (MADDs), and riboflavin metabolism or transport genetic defects can also cause MADD or varying degrees of progressive neurodegenerative diseases such as riboflavin transporter deficiency (RTD) [3]. There are three human riboflavin transporter (RFVT) homologs: RFVT 1 to 3, encoded by genes SLC52A1 to SLC52A3, respectively [4]. RFVTs are widely distributed in the body and SLC52A1 is highly expressed in the placenta and intestine [3]. SLC52A2 is rather ubiquitously expressed, mainly in the brain, and, although SLC52A3 is most highly expressed in the testes, which also expressed in the intestine and prostate [3]. There are three types of RTDs and these

Riboflavin 1 Transporter Deficiency: Novel SLC52A1 Variants and Expansion of the Phenotypic Spectrum

“…In contrast, patient 2 had a normal acylcarnitine profile. It is difficult to assess whether the clinical symptoms of our patients can really be attributed to RFVT1 deficiency, but the clinical presentation of patient 2 resembles the clinical phenotype of the patient reported by Kang et al [10]. However, the genetic variant identified in patient 2 is classified as a variant of unknown significance.…”

“…While RVFT2 and RVFT3 deficiencies are clinically well-characterized disorders, only five cases of RFVT1 deficiency from three families have been reported so far [2,[8][9][10]. An overview of the genetic findings as well as clinical symptoms of all known cases is shown in Table 1.…”

“…Kang et al [10] reported a previously healthy 4-month-old girl that presented with recurrent seizures. There were no prenatal or perinatal problems, and she showed normal growth and development.…”

“…Testing of her parents revealed heterozygous deletions in exons 1-5 of SLC52A1 in her father and a 25% decrease in DNA concentration in the mother, indicating a 25% allele frequency for the exon 3 deletion allele (mosaic heterozygous exon 3 deletion) in the child. Her father was healthy and had no symptoms related to this mutation; however, no biochemical analyses are reported [10].…”

“…RFVT1 deficiency is caused by autosomal dominant, heterozygous SLC52A1 pathogenic variants. To our knowledge, only five cases of RFVT1 deficiency from three families have been reported so far [2,[8][9][10]. While newborns and infants with SLC52A1 variants mainly showed MADDlike symptoms, individuals identified in adulthood were usually asymptomatic apart from a typical biochemical profile.…”