SLC52A1 – Ariboflavinosis

Ariboflavinosis is a spectrum of riboflavin (vitamin B2) deficiency disorders characterized by impaired energy metabolism and neurological dysfunction. The SLC52A1 gene encodes the riboflavin transporter RFVT1, which mediates intestinal and placental uptake of riboflavin and its cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Disruption of RFVT1 reduces systemic flavin availability, leading to biochemical signatures akin to multiple acyl-CoA dehydrogenase deficiency and variable clinical presentations (PMID:22231380).

Genetic evidence for SLC52A1 involvement in ariboflavinosis stems from autosomal dominant inheritance of heterozygous pathogenic variants in seven affected individuals from five families. Two novel variants were described: c.68C>A (p.Ser23Tyr) and c.3G>A (p.Met1Ile) in SLC52A1 detected in adults and infants with multiple acyl-CoA dehydrogenase deficiency–like biochemistry (PMID:37510312). No formal segregation beyond proband identification has been reported to date.

Functional studies using Rfvt1 knockout mouse models demonstrate embryonic lethality or severe neurological impairment concordant with critical roles in flavin transport. Tissue-specific expression analyses confirm high RFVT1 levels in intestine and placenta, and riboflavin supplementation rescues phenotypes in related transporter deficiencies, supporting haploinsufficiency as the mechanism (PMID:40603088).

No reports currently dispute the association of SLC52A1 variants with riboflavin deficiency syndromes. The available genetic and experimental data, although limited by small case numbers, show concordant findings across human and animal models.

Together, these findings establish a limited but consistent role for heterozygous SLC52A1 variants in autosomal dominant ariboflavinosis. Early genetic diagnosis enables timely riboflavin supplementation, which can ameliorate metabolic derangements and improve clinical outcomes.

Key Take-home: SLC52A1 haploinsufficiency underlies a dominantly inherited riboflavin deficiency syndrome responsive to high-dose vitamin B2 therapy.

References

• Journal of inherited metabolic disease • 2012 • Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10) PMID:22231380
• Genes • 2023 • Riboflavin 1 Transporter Deficiency: Novel SLC52A1 Variants and Expansion of the Phenotypic Spectrum PMID:37510312
• Biological & pharmaceutical bulletin • 2025 • Identification and Physiological Analysis of Novel Riboflavin Transporter RFVT PMID:40603088

Evidence Based Scoring (AI generated)