The effects of supplementation of riboflavin have been reported in 13 patients
[3, 5–9]. Eleven patients were treated with oral riboflavin, in two patients intravenous riboflavin supplementation was reported. Most patients were treated with a dose of 10mg/kg/day. The mean age at the start of treatment was known for 11 patients and was 6.9 years (range: 3 months–17 years).
Eight of 13 treated patients demonstrated a strong clinical improvement. Seven of these patients were treated orally: one patient initially with a dose of 150 mg/day at age 10 (which will be less than 10 mg/kg/day) which was increased to 450 mg/day after 3 months, five with a dose of 10 mg/kg/day, and one patient with a dose of and 25 mg/kg/day. One patient was treated intravenously with 200 mg/day at age 9 (less than 10 mg/kg/day). The first signs of improvement were seen within days in some patients
[3, 5] with a more gradual improvement over many months in others
[3, 5, 6]. Improvement was seen in muscle strength, motor function, respiration, hearing, and vision with a full recovery in some. Five patients were on mechanical ventilation (4 tracheostomy and 1 noninvasive ventilation) at the start of treatment. In all 4 patients with a tracheostomy, ventilation could be decreased or stopped. In the patient on noninvasive ventilation an improvement in diaphragm function was reported
[3, 5, 6].
In 6 of 8 riboflavin responsive patients MADD-like abnormalities were found in the acylcarnitine profile before treatment
[3, 5, 8, 9] and in 4 of these patients deficient flavin levels were found as well. All acylcarnitine profiles and flavin levels normalised after riboflavin supplementation. Notably, 2 patients with normal acylcarnitine profiles, 3 patients with normal flavin levels, and one with unknown flavin levels before treatment was started, did demonstrate a strong clinical improvement after the start of treatment as well
In all 8 patients who improved on riboflavin supplementation mutations were found in riboflavin transporter genes: in 6 patients mutations were demonstrated in the SLC52A3 gene, whereas in 2 patients mutations were demonstrated in the SLC52A2 gene
In 5 patients no improvement was demonstrated with riboflavin supplementation. Two of these patients were treated for a very short period: 1 discontinued treatment because of intolerance to oral riboflavin
, and in one patient treatment was stopped already after 1 week due to lack of clinical improvement
. This last patient did demonstrate improvement in the following months but the relation between the improvement and the riboflavin supplementation has remained unclear. All three patients on prolonged riboflavin supplementation are reported to have a stable clinical situation but without improvement. The three stable patients and the patient who stopped treatment because of intolerance were all treated orally with 10 mg/kg/day. The patient who was considered unresponsive after one week of treatment was treated with 10 mg/kg/day intravenously. In four of the patients without improvement, acylcarnitine profiles and flavin levels had been studied and no abnormalities were found.
Mutations in the hRFT2 gene were found in two patients who did not improve on riboflavin: one of the patients with a stable clinical course and the patient in whom treatment was stopped after 1 week for lack of effect. The two patients with a stable condition but no clinical improvement after treatment, and the patient reported to be intolerant of riboflavin supplementation did not demonstrate mutations in SLC52A1, SLC52A2, or SLC52A3.