Brown-Vialetto-Van Laere and Fazio Londe syndromes: defects of riboflavin transport with biochemical similarities to multiple acyl-CoA dehydrogenation defects (MADD)

Excerpt

Riboflavin-responsive defects of electron transfer were first described in the 1980s as mild variant forms of MADD or glutaric acidemia type II (Gregersen et al 1982; Amendt and Rhead 1986). Some of these patients were shown to have defects in ETF and ETF dehydrogenase but a number of patients remained in whom the biochemical and molecular defects remained elusive (Roettger et al 1992). It was postulated that these patients may have defect(s) of riboflavin transport or abnormalities in downstream flavin metabolism to form the active FAD/FMN cofactors required for facilitating electron transfer. Treatment of some of these patients with high dose riboflavin tended to normalize the abnormal metabolite profiles. Treatment with high dose riboflavin was also subjectively claimed to improve the clinical phenotype, a difficult judgment given the mild and intermittent nature of the phenotype. The phenotype of most of the cases of riboflavin-responsive MADD was that of stress-induced myopathy (de Visser et al 1986; DiDonato et al 1989). …