Flavin adenine dinucleotide status and the effects of high-dose riboflavin treatment in short-chain acyl-CoA dehydrogenase deficiency.
Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inborn error, biochemically characterized by increased plasma butyrylcarnitine (C4-C) concentration and increased ethylmalonic acid (EMA) excretion and caused by rare mutations and/or common gene variants in the SCAD encoding gene. Although its clinical relevance is not clear, SCADD is included in most US newborn screening programs. Riboflavin, the precursor of flavin adenine dinucleotide (FAD, cofactor), might be effective for treating SCADD. We assessed the FAD status and evaluated the effects of riboflavin treatment in a prospective open-label cohort study involving 16 patients with SCADD, subdivided into mutation/mutation (mut/mut), mutation/variant (mut/var), and variant/variant (var/var) genotype groups. Blood FAD levels were normal in all patients before therapy, but significantly lower in the mut/var and var/var groups compared with the mut/mut group. Riboflavin treatment resulted in a decrease in EMA excretion in the mut/var group and in a subjective clinical improvement in four patients from this group. However, this improvement persisted after stopping treatment. These results indicate that high-dose riboflavin treatment may improve the biochemical features of SCADD, at least in patients with a mut/var genotype and low FAD levels. As our study could not demonstrate a clinically relevant effect of riboflavin, general use of riboflavin cannot be recommended.
van Maldegem
Bianca T
BT
Department of Pediatrics, University of Amsterdam, Amsterdam, the Netherlands. B.van.Maldegem@gelre.nl
Duran
Marinus
M
Wanders
Ronald J A
RJ
Waterham
Hans R
HR
Wijburg
Frits A
FA
D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000097:blood* / Q000652:urine; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000652:urine; D008297:Male; D008314:Malonates / Q000652:urine; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D012256:Riboflavin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage*
D015415:Biomarkers; D008314:Malonates; D014803:Vitamin B Complex; D005182:Flavin-Adenine Dinucleotide; C427065:butyrylcarnitine; C038080:ethylmalonic acid; D044926:Butyryl-CoA Dehydrogenase; D002331:Carnitine; D012256:Riboflavin