Rapid Communication

Journal of Inherited Metabolic Disease

, Volume 34, Issue 1, pp 159-164

Open Access This content is freely available online to anyone, anywhere at any time.

Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

  • Annet M. BoschAffiliated withDepartment of Pediatrics, Academic Medical Center, University of AmsterdamDepartment of Pediatrics, Academic Medical Center (H7 270), University Hospital of Amsterdam Email author 
  • , Nico G. G. M. AbelingAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam
  • , Lodewijk IJlstAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam
  • , Hennie KnoesterAffiliated withDepartment of Pediatrics, Academic Medical Center, University of Amsterdam
  • , W. Ludo van der PolAffiliated withRudolf Magnus Institute of Neuroscience, Department of Neurology and Pediatric Neuromuscular Center ‘Spieren Voor Spieren’, University Medical Center Utrecht
  • , Alida E. M. StroomerAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam
  • , Ronald J. WandersAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam
  • , Gepke VisserAffiliated withDepartment of Metabolic Diseases, Wilhelmina Children’s Hospital
  • , Frits A. WijburgAffiliated withDepartment of Pediatrics, Academic Medical Center, University of Amsterdam
    • , Marinus DuranAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam
    • , Hans R. WaterhamAffiliated withLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam

Abstract

We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafness.