Systemic carnitine deficiency due to lack of electron transfer flavoprotein:ubiquinone oxidoreductase.
A child with myopathy and systemic carnitine deficiency died at age 8 years in an acute metabolic attack. He had glutaric aciduria type II, and his cultured fibroblasts contained normal activity of four different acyl CoA dehydrogenases, but there was deficiency of electron transfer flavoprotein:ubiquinone oxidoreductase (ETF-QO). This enzyme is thought to reduce coenzyme Q in the respiratory chain, funneling reducing equivalents from seven flavoproteins in the beta-oxidation of acyl CoAs. There was massive urinary excretion of the short-chain acylcarnitines that accumulated in mitochondria as a result of the ETF-QO defect. Carnitine therefore acts as a buffer for excessive accumulation of intramitochondrial acyl CoAs, and defective beta-oxidation can cause carnitine insufficiency.
S
S
Di Donato
F E
FE
Frerman
M
M
Rimoldi
P
P
Rinaldo
F
F
Taroni
U N
UN
Wiesmann
D000108:Acetylcarnitine / Q000032:analysis; D000328:Adult; D000818:Animals; D002331:Carnitine / Q000172:deficiency*; D002417:Cattle; D002648:Child; D044927:Electron-Transferring Flavoproteins; D044943:Fatty Acid Desaturases / Q000172:deficiency* / Q000378:metabolism / Q000652:urine; D005347:Fibroblasts / Q000378:metabolism; D005977:Glutarates / Q000652:urine; D006801:Humans; D007506:Iron-Sulfur Proteins; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors; D013552:Swine
D044927:Electron-Transferring Flavoproteins; D005977:Glutarates; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D000108:Acetylcarnitine; D044943:Fatty Acid Desaturases; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C035736:glutaric acid; D002331:Carnitine