Abstract
Rationale:
Brown-Vialetto-Van Laere syndrome, currently recognized within the spectrum of riboflavin transporter deficiency type 3 (RTD3), is a rare inherited neurometabolic disorder associated with pathogenic variants in
SLC52A3
. It typically presents with progressive sensorineural hearing loss, pontobulbar dysfunction, peripheral neuropathy, and respiratory involvement. Diagnosis may be delayed because routine metabolic and neuromuscular investigations can be unrevealing despite a characteristic clinical phenotype.
Patient concerns:
A young Asian man presented with several years of progressive bilateral hearing loss followed by worsening dysphagia to solids and liquids, symmetrical limb weakness, muscle wasting, and acute-on-chronic dyspnea. Two siblings had previously died at a young age after developing a similar sequence of hearing impairment, dysphagia, limb weakness, and unexplained respiratory failure.
Diagnoses:
Neurological examination showed tongue atrophy with fasciculations, thenar wasting, bifacial weakness, mild ptosis, diminished gag reflex, and symmetrical limb weakness. Audiometry confirmed profound bilateral sensorineural hearing loss. Nerve conduction studies demonstrated predominantly motor axonal neuropathy, while electromyography showed chronic and active denervation. Repetitive nerve stimulation, cerebrospinal fluid analysis, magnetic resonance imaging, creatine kinase levels, and metabolic investigations were unrevealing. Targeted genetic testing detected pathogenic SLC52A3 variants, confirming RTD3/ Brown-Vialetto-Van Laere syndrome.
Interventions:
High-dose oral riboflavin was initiated empirically at 40 mg/kg/day in 3 divided doses before genetic confirmation because of progressive respiratory compromise and strong clinical suspicion. Supportive management included nutritional support and nocturnal noninvasive ventilation with bilevel positive airway pressure.
Outcomes:
The patient showed marked improvement after riboflavin initiation. Respiratory effort improved within several days, and forced vital capacity increased from 35% to 50% of predicted within 1 week. Limb strength improved, and by 8 weeks the patient had gained 3 kg with stabilization of dysphagia and improved oral intake. At 6 months, neurological status remained stable without further electrophysiological progression. Riboflavin was well tolerated.
Lessons:
RTD3 should be considered in young patients with progressive sensorineural hearing loss associated with bulbar dysfunction, motor neuropathy, or respiratory weakness, particularly when family history is suggestive. Recognition of the characteristic phenotype, targeted genetic testing, and prompt initiation of high-dose riboflavin may substantially alter the clinical course of this potentially treatable disorder.