Glutaric Acidemia Type I (GA-I)

Progressive neurologic disorder caused by a genetically transmitted inborn error of metabolism of glutaric acid.

Glutaric Aciduria; Glutaryl-CoA Dehydrogenase Deficiency.

May be more prevalent in Sweden and in Amish Pennsylvania. Affects males and females equally.

Autosomal recessive. Defective gene coding for glutaryl-CoA dehydrogenase located on chromosome 19. Forty-five mutations have been identified.

Deficiency of glutaryl-CoA dehydrogenase, a mitochondrial flavin adenine dinucleotide (FAD)-dependent enzyme of the liver and kidney. This enzyme normally catalyzes the conversion of glutaryl-CoA to glutaconyl-CoA, which is an intermediate in the catabolism of lysine, hydroxylysine, and tryptophan. Deficiency of glutaryl-CoA dehydrogenase results in accumulation of glutaric acid in the body, which leads to progressive neurologic damage (degeneration of the basal ganglia of the brain) with acute episodes often triggered by stress such as infections or surgery.

During acute episodes, high concentrations of glutaric acid are found in blood and urine. Enzyme activity may be assayed in leukocytes or fibroblasts. Prenatal diagnosis is available (deficiency of glutaryl-CoA dehydrogenase activity in cultured chorionic villi/amniocytes; inconstantly, elevated glutaric acid levels in the amniotic fluid).

Early development may be normal. The pediatric patient develops progressive dystonia and choreoathetosis. Acute encephalopathy often develops between 6 to 18 months of age, causing striatal damage with severe neuronal loss. Spongiform changes restricted to brainstem white matter and mild lymphocytic infiltrates have been described. Acute exacerbation may occur after a minor infection, presenting with vomiting, ketosis, seizures, and coma. Death commonly occurs during one of these episodes. A low-protein diet and high doses of riboflavin may result in clinical improvement in some patients.

Maintain adequate hydration. Check acid-base status. Assess neurologic status.

Periods of stress, such as surgery, may precipitate acute deterioration. Adequate hydration should be ensured perioperatively and acid-base status monitored during major surgery. Severity of neurologic abnormalities may dictate changes in anesthetic technique, for example, children with bulbar involvement may be at risk for pulmonary aspiration.

No agents specifically contraindicated. Neurologic status may warrant avoidance of drugs that can precipitate seizures, such as enflurane and meperidine.

Glutaric Acidemia Type II (GA-II): Progressive neurologic disorder caused by a genetically transmitted inborn error of metabolism in which the body cannot oxidize fatty acids. Typical clinical features include respiratory distress, muscular hypotonia, sweaty odorous feet, and death often occuring in the neonatal period.