Progressive inherited neurologic disorder caused by a genetically transmitted inborn error of metabolism leading to break down completely the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products, ie, glutaric acid, glutaryl-CoA, 3-hydroxyglutaric acid, and glutaconic acid can accumulate and cause damage to the brain. The basal ganglias are most often affected which may cause neurological irregular movement. Mental retardation may occur.
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 is 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. GA1 causes secondary carnitine deficiency, as glutaric acid, like other organic acids, is detoxified by carnitine. 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 and 18 months of age, causing striatal damage with severe neuronal loss. Spongiform changes restricted to brain stem 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.
Precautions before anesthesia
Maintain adequate hydration. Check acid-base status, including glucose and lactate blood levels. 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. Strategies for anesthetic management should include prevention of pulmonary aspiration, dehydration, hyperthermia and catabolic state, adequate analgesia to minimize surgical stress, and avoidance of ...