A Novel Homozygous Mutation Of SLC52A3 Gene Associated With Brown-Vialetto-Van Laere Syndrome (BVVL) (S42.001)

Objective: To describe a case of a child with typical clinical features and molecular confirmation of BVVL with impressive clinical response to enteral riboflavin. Background: BVVL is a rare neurological disorder described by Brown, Vialetto, and Van Laere as progressive pontobulbar palsy and sensorineural deafness with rapid deterioration and death secondary to respiratory failure. Age at presentation varies from infancy to the 5th decade, affecting females more than males (3:1). BVVL is caused by mutations in the SLC52A3, SLC52A2 and SLC52A1 genes (riboflavin transporter genes) with symptomatic improvement reported with administration of riboflavin. Design/Methods: A 32-month-old Hispanic female presented with sensorineural hearing loss and speech regression that began six months prior to admission, with two months of ptosis and wide-based gait and one week of choking when eating and sleeping. Family history was significant for a brother who died at 4 ½ years of age with similar presentation excluding hearing loss. Exam showed a non-verbal girl with bilateral ptosis, facial diplegia, weak gag reflex, and ataxia. She was diagnosed clinically with probable BVVL. Metabolic testing including CSF and brain MRI were normal. Laryngoscopy revealed bilateral vocal cord paralysis and ultrasonography revealed unilateral diaphragm weakness. Results: Molecular testing demonstrated a novel homozygous missense mutation in exon 4 of the SLC52A3 gene (p.Cys386Arg), one of three genes known to cause BVVL. The patient was started on high dose riboflavin, initially orally and later through gastrostomy tube (secondary to dysphagia). Gait, facial diplegia, and ptosis improved significantly over four months, with gradual recovery of hearing detected by audiogram. Conclusions: We report a girl with progressive pontobulbar palsy and sensorineural hearing loss with a confirmed novel homozygous SLC52A3 mutation who experienced dramatic improvement with high dose riboflavin as per the protocol pioneered by Bosch et al. Because of this condition’s potentially rapid progression and poor prognosis, prompt clinical recognition of BVVL and institution of high dose riboflavin could be life saving. Disclosure: Dr. Naik has nothing to disclose. Dr. Chopra has nothing to disclose. Dr. Pletcher has nothing to disclose. Dr. Gordhan has nothing to disclose. Dr. Ming has nothing to disclose.