Riboflavin transporter deficiency associated with a homozygous nonsense slc52a3 variant: first genotypeÓ?phenotype correlation and literature review

Objective: The objective of the study was to describe a rare case of riboflavin (RF) transporter deficiency (RTD) caused by a homozygous nonsense variant in SLC52A3 not previously associated with a detailed clinical phenotype, and to review the clinical features, genetic findings, and therapeutic response reported in the literature.Methods: We report the clinical, neurophysiological, and genetic findings of an infant diagnosed with RTD.Molecular analysis was performed using next-generation sequencing, with variant confirmation by Sanger sequencing.Variant interpretation followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.In addition, a narrative review of the literature was conducted, focusing on previously reported cases of SLC52A2 and SLC52A3 mutations.Results: The patient presented with progressive neuromuscular involvement, including hypotonia, dysphagia, and respiratory failure requiring ventilatory support.Genetic testing identified a homozygous nonsense variant in SLC52A3, predicted to result in loss of protein function.This variant has been previously deposited in ClinVar by the testing laboratory but has not been reported in published clinical cases to date.Despite early initiation of high-dose RF supplementation, no significant clinical improvement was observed.Review of the literature suggests that missense variants are more frequently associated with partial therapeutic response, whereas severe loss-of-function variants, such as nonsense mutations, are associated with poorer outcomes.Conclusions: RTD should be considered in infants with progressive neuromuscular symptoms and respiratory compromise.Although early RF supplementation remains essential, this case highlights that therapeutic response may be limited in patients harboring severe loss-of-function variants, underscoring the importance of genotype-phenotype correlations for prognosis and clinical counseling.