Abstract

1. 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.

   
   

2. 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. Complete enzyme defects, especially of ETF-QO, are often associated with multiple congenital anomalies, including renal cystic dysplasia, and death in infancy.

   
   

3. 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.

   
   

4. Prenatal diagnosis of glutaric acidemia type II is possible in some cases by demonstrating increased concentrations of glutaric acid in amniotic fluid, acylcarnitine esters in maternal urine, or impaired substrate oxidation by cultured amniocytes.

   
   

5. There is no effective treatment for glutaric acidemia type II patients who present in early infancy. Treatment with riboflavin, glycine, and L-carnitine and diets restricted in fat and protein may be effective in less severely affected patients.

   
   

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