Autosomal Dominant Brown-Vialetto-Van Laere Syndrome: A New Case and Systematic Review of a Treatable Neurometabolic Disorder

Background : Brown-Vialetto-Van Laere (BVVL) syndrome is a rare neurodegenerative disorder caused by mutations in SLC52A2 or SLC52A3 , impairing riboflavin transport. It typically presents with sensorineural hearing loss, progressive ponto-bulbar palsy, peripheral neuropathy, and occasional respiratory compromise. While most cases follow an autosomal recessive (AR) inheritance pattern, around 30 autosomal dominant (AD) cases have been reported. We describe a novel case of pediatric-onset BVVL caused by a heterozygous SLC52A3 variant and perform a literature review of AD BVVL cases. The 18-year-old patient initially presented at age 15 with bilateral hearing loss, followed by progressive cranial neuropathies and bulbar symptoms. Genetic analysis revealed a heterozygous SLC52A3 variant of uncertain significance, inherited from her asymptomatic mother. High-dose riboflavin therapy (up to 75 mg/kg/day) led to significant clinical improvement, supporting the pathogenicity of the variant. Results : A review of 31 additional AD BVVL cases revealed that disease onset is typically later than in AR forms, with no reported deaths and carrier family members often asymptomatic. Serum acylcarnitine profiles are normal, and cerebrospinal fluid may show elevated proteins. Riboflavin supplementation always improved symptoms, including respiratory function, strength, and hearing. Conclusions : Our findings suggest that AD BVVL has a milder course than AR cases, with later onset, no mortality, and broader inter and intra-familial phenotypic variability, indicating variable expressivity. Diagnosis is challenging due to normal acylcarnitine profiles and nonspecific cerebrospinal fluid findings. Early recognition and riboflavin supplementation are crucial, and a trial of riboflavin should be considered in all patients with a clinical suspicion, even with inconclusive genetic findings.