Autosomal dominant Brown-Vialetto-Van Laere syndrome: a new case and systematic review of a treatable neurometabolic disorder

Abstract 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 according to PRISMA guidelines Results 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, initially classified as 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 reclassification of the variant as pathogenic. A review of 31 additional AD BVVL cases revealed that disease onset is typically later than in AR forms, with no reported deaths and heterozygous family members often asymptomatic. Serum acylcarnitine profiles are normal, and cerebrospinal fluid may show elevated protein. Riboflavin supplementation always improved symptoms, including respiratory function, strength, and hearing. Conclusions AD BVVL is a treatable disorder with incomplete penetrance and broad phenotypic variability. It should be suspected in adolescents or young adults presenting with progressive sensorineural hearing loss and other cranial neuropathies, and acylcarnitine testing is not a useful diagnostic tool. Given the safety profile of riboflavin and the potential reversibility of symptoms, early empirical treatment should be initiated when when BVVL is strongly suspected clinically, while extensive genetic evaluations and family screening are pursued.