[Pubmed] Biomarker-Guided Diagnosis of Riboflavin Transporter Deficiency Presenting as Seronegative Myasthenia Gravis: A

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Genet Test Mol Biomarkers. 2026 Sep 26:19450265261493084. doi: 10.1177/19450265261493084. Online ahead of print.

ABSTRACT

BACKGROUND: Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare, treatable neurodegenerative disorder caused by riboflavin transporter gene variants (SLC52A2, SLC52A3). Early symptoms can mimic neuromuscular junction disorders, causing diagnostic delays.

CASE PRESENTATION: A 3.5-year-old girl from consanguineous parents presented at 2.5 years with isolated bilateral ptosis, later developing dysphagia, dysphonia, facial diplegia, stridor, and respiratory compromise. Examination revealed tongue atrophy with fasciculations and bulbar weakness but normal limb strength. Diagnosed with seronegative myasthenia gravis, she failed to respond to corticosteroids, pyridostigmine, salbutamol, and intravenous immunoglobulin. Absence of fatigability, lower motor neuron signs, and a sibling history of hearing loss and bulbar palsy prompted genetic testing revealed a homozygous missense variant in SLC52A3 (c.670T > C; p.Phe224Leu). High-dose riboflavin (up to 50 mg/kg/day) led to gradual improvement in bulbar function, resolution of stridor, and respiratory stabilization, though ptosis and tongue fasciculations persisted.

CONCLUSION: This report is novel in using clinical response to riboflavin as a functional biomarker for riboflavin transporter deficiency (RTD) in a patient with a variant of uncertain significance, unlike prior cases with definitive genetics. Empiric riboflavin challenge offers a practical framework when genetic results are ambiguous. RTD should be suspected in children with treatment-resistant, non-fluctuating ptosis and bulbar weakness, particularly with consanguinity or family history of hearing loss and bulbar palsy. Early high-dose riboflavin prevents decline, while immunosuppression is ineffective and potentially harmful.

PMID:42799589 | DOI:10.1177/19450265261493084


Source: https://pubmed.ncbi.nlm.nih.gov/4279958 ... 5&v=2.20.1