Late-onset form of beta-electron transfer flavoprotein deficiency.
Multiple acyl-CoA-dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) are a group of metabolic disorders due to deficiency of either electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO). We report the clinical features and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H]palmitate and [9,10-3H]myristate in fibroblasts, suggesting MAD deficiency. In agreement with these findings, mutational analysis of the ETF/ETFDH genes demonstrated an ETFB missense mutation 124T>C in exon 2 leading to replacement of cysteine-42 with arginine (C42R), and a 604_606AAG deletion in exon 6 in the ETFB gene resulting in the deletion of lysine-202 (K202del). The present report delineates further the phenotype of mild beta-ETF deficiency and illustrates that the differential diagnosis of GAII is readily achieved by mutational analysis.
Curcoy
A
A
Department of Paediatrics, Hospital Sant Joan de Déu, Barcelona, Spain. campistol@hsjdbcn.org
Olsen
R K J
RK
Ribes
A
A
Trenchs
V
V
Vilaseca
M A
MA
Campistol
J
J
Osorio
J H
JH
Andresen
B S
BS
Gregersen
N
N
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D001120:Arginine / Q000737:chemistry; D002331:Carnitine / Q000097:blood; D003545:Cysteine / Q000737:chemistry; D004252:DNA Mutational Analysis; D044927:Electron-Transferring Flavoproteins / Q000172:deficiency* / Q000235:genetics*; D004583:Electrons; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D017353:Gene Deletion; D005977:Glutarates / Q000652:urine; D006801:Humans; D007231:Infant, Newborn; D007506:Iron-Sulfur Proteins / Q000172:deficiency* / Q000235:genetics*; D008239:Lysine / Q000737:chemistry; D020125:Mutation, Missense; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency* / Q000235:genetics*; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype
D044927:Electron-Transferring Flavoproteins; D005977:Glutarates; D007506:Iron-Sulfur Proteins; D001120:Arginine; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C035736:glutaric acid; D008239:Lysine; D003545:Cysteine; D002331:Carnitine; D010100:Oxygen