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
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
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
Bjugstad KB, Goodman SI, Freed CR: Age at symptom onset predicts severity
of motor impairment and clinical outcome of glutaric acidemia type 1. J Pediatr
Funk CB, Prasad AN, Frosk P, et al: Neuropathological, biochemical and molecular
findings in a glutaric acidemia type I cohort. Brain 128;711, 2005.