The
Brown-Vialetto-Van Laere syndrome is a rare
neurological disorder which may present at all ages with sensorineural
deafness,
bulbar palsy and respiratory compromise.
Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2)
riboflavin transporter. In these patients
riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of
riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human
riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were
bulbar palsy,
hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with
riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable
clinical course and treatment was stopped early in two patients. Abnormalities in plasma
flavin levels and/or plasma
acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma
flavin levels and
acylcarnitine profiles demonstrated a striking clinical improvement on
riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months.