Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency.
A newborn female presented on the first day of life with clinical and biochemical findings consistent with multiple acyl-CoA dehydrogenase deficiency (MADD). Riboflavin supplementation corrected the biochemical abnormalities 24 h after commencing the vitamin. In vitro acylcarnitine profiling in intact fibroblasts both in normal and riboflavin depleted media showed normal oxidation of fatty acids excluding defects in electron transfer flavoprotein (ETF), or ETF ubiquinone oxidoreductase (ETF:QO), or a genetic abnormality in flavin metabolism. In addition, sequencing of the genes encoding ETF and ETF:QO in the proband did not reveal any pathogenic mutations. Determination of the maternal riboflavin status after delivery showed that the mother was riboflavin deficient. Repeat testing done two years after the infant's birth and while on a normal diet showed that the mother was persistently riboflavin deficient and showed a typical MADD profile on plasma acylcarnitine testing. A possible genetic defect in riboflavin transport of metabolism in the mother is postulated to be the cause of the transient MADD seen in the infant. Sequencing of the SLC16A12, RFK and FLAD1 genes encoding key enzymes in riboflavin transport of metabolism in the mother did not identify any pathogenic mutations. The underlying molecular basis of the mother's defect in riboflavin metabolism remains to be established.
Chiong
M A
MA
Western Sydney Genetics Program, Children's Hospital at Westmead, and Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia.
Sim
K G
KG
Carpenter
K
K
Rhead
W
W
Ho
G
G
Olsen
R K J
RK
Christodoulou
J
J
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D044927:Electron-Transferring Flavoproteins / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D044342:Malnutrition; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D009035:Mothers; D010084:Oxidation-Reduction; D012257:Riboflavin Deficiency / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000201:enzymology / Q000473:pathology; D027981:Symporters; D014815:Vitamins / Q000008:administration & dosage
D044927:Electron-Transferring Flavoproteins; D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014815:Vitamins; C116917:acylcarnitine; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine