Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to deletion of p.ser495 in the FAD synthase

Activity: Talk or presentation typesLecture and oral contribution

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Signe Mosegaard - Invited speaker

Multiple acyl-CoA dehydrogation deficiency (MADD) is an autosomal inherited disease characterized by dysfunction of multiple mitochondrial flavoprotein dehydrogenases. Riboflavin responsive forms of MADD have been explained mainly by gene variations in the electron transfer flavoprotein dehydrogenase (ETFDH) and more recently by variations in the riboflavin transporter (RFT) genes, the latter once with mostly progressive neurological symptoms.
We present two siblings suffering from riboflavin responsive MADD, one present with cardiomyopathy at 2 months of age and the other in the neonatal period, but with no disease-causing variations in the ETFDH or RFT genes. Sequence analysis revealed that both siblings were homozygous for a deletion of c.1484_1486 in the FLAD1 gene, causing deletion of Serine-495 in the FAD synthase, which converts FMN into the obligate FAD cofactor for the dysfunctional flavoprotein dehydrogenases in MADD.
Western blot analysis showed decreased levels of FAD synthase in the patient’s fibroblast cells as compared to controls suggesting that deletion of Serine-495, which is located in the highly conserved PAPS reductase domain, gives rise to an unstable protein.
This is the first report of a disease-causing FLAD1 variation and it expands the number of disease genes and symptoms in a heterogeneous treatable disease.
3 Sep 2014

Event (Conference)

TitleSSIEM 2014
Abbreviated titleSSIEM
Date02/09/201405/09/2014
LocationCongress Innsbruck, Rennweg 3
CityInnsbruck
CountryAustria

ID: 87392869