DeCure for Brown-Vialetto-van Laere syndrome 1

Brown-Vialetto-van Laere syndrome is a rare disorder characterised by progressive pontobulbar palsy and sensorineural deafness. More than 30 cases had been reported by 2000. A 1990 report described a female patient whose father, paternal uncle, and possibly a paternal first cousin had neurosensory deafness, and a paternal aunt had clinical symptoms indicative of the syndrome; the authors raised the possibility of autosomal dominant inheritance or X-linked inheritance, in addition to the more commonly assumed autosomal recessive pattern. A 1991 case described a Caucasian girl with slowly progressive sensory neural deafness and bulbar and spinal muscle weakness; as the condition progressed, major disabilities included dysphagia, respiratory muscle weakness, and postural hypotension, and treatment with gastrostomy feedings, oxygen, and fludrocortisone acetate produced worthwhile functional improvement.

In 2015, exome sequencing of a 20-month-old female with a rapidly progressing neurological disorder initially thought to be autoimmune led to a diagnosis of Brown-Vialetto-van Laere syndrome 2. The therapy plan changed from steroids and precautionary chemotherapy to high-dose riboflavin. Improvements were reported quickly, including in motor strength after one month. The authors stated that the correct diagnosis and appropriate treatment would have been unlikely without exome sequencing. Another 2015 report described two siblings with a novel homozygous mutation in SLC52A3. The first sibling required mechanical ventilation for respiratory insufficiency; after high-dose riboflavin, all clinical symptoms resolved. The second sibling, found to have the same mutation but symptom-free, was started on riboflavin empirically and on follow-up developed no neurologic or metabolic problems, with entirely normal growth and development. The authors suggested that with proper diagnosis and early high-dose riboflavin treatment, complete reversal of neurologic deficits is possible.

A 2018 report described a child with genetically proven Brown-Vialetto-van Laere syndrome where prompt treatment with riboflavin showed good results. The syndrome is now understood to be an autosomal-recessive inherited disease caused by mutations in intestinal riboflavin transporter genes, and it forms a continuous spectrum with Fazio-Londe syndrome. The evidence is limited to case reports and small case series; no controlled trials have been conducted. What is still missing is systematic prospective data collection, standardised outcome measures, and a formal trial design that can distinguish the natural history of different genotypes from the effect of riboflavin dose, timing, and duration. Patient stratification by mutation type and age at treatment initiation remains unexplored in any comparative study.