Correct!
5. All of the above
The constellation of weakness, fatty liver, hypoglycemia and hyperammonemia suggest a problem with fatty acid metabolism: either carnitine deficiency, deficiencies of carnitine palmitoyltransferase deficiency (which transport FA into the mitochondria), defects of acyl dehydrogenases that participate in beta-oxidation of fatty acids, or a defect of electron transport flavoprotein (which resides in the electron transport chain and is the entry point for FADH2 that delivers the high-energy chemical bonds from FA metabolism into the electron transport chain) (1).
Disorders of fatty acid metabolism can cause metabolic myopathy. They are sometimes misdiagnosed as muscular dystrophies, inflammatory myopathies or Reye’s syndrome when the serum ammonia is elevated. Classification is by the primary energy source affected-glycogen storage, purine metabolism, lipid storage or abnormalities of the electron transport chain.
Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETF-QO) are nuclear encoded proteins through which electrons from flavoprotein acyl CoA dehydrogenases, dimethylglycine dehydrogenase, and sarcosine dehydrogenase enter ubiquinone in the respiratory chain. Inherited defects of either protein cause glutaric acidemia type II. Glutaric acidemia type II is characterized clinically by hypoketotic hypoglycemia and metabolic acidosis; pathologically by fatty infiltration of the liver, heart, and kidneys; and biochemically by a diagnostic organic aciduria.
Primary defects of ETF-QO and those of either ETF subunit are inherited as autosomal recessive traits. Several pathogenic mutations have been identified in the genes for ETF-QO and the α-ETF subunit. No single ETF-QO mutation is common, but of six that have been identified in the α-ETF gene, αT266M may account for about 40 percent of mutant alleles.
Our patient had a markedly elevated urine glutaric acid consistent with electron transport flavoprotein defect. This was confirmed by genetic analysis.
Which of the following are recommended to treat electron transport flavoprotein defect? (Click on the correct answer to procced to the fourth and final page)