Glutaric acidemia, type I (GA I), was first described in 1975. The disease is caused by a genetic deficiency of the enzyme, glutaryl-CoA dehydrogenase (GCD), which leads to the buildup of glutaric acid in the tissues and its excretion in the urine of affected patients. GCD is involved in the catabolism of the amino acids, lysine, hydroxylysine, and tryptophan.
Newborn screening using tandem mass spectrometry of the heel stick dried blood spot identifies patients with GA I by the presence of glutaric acid covalently bound to carnitine (C5-dicarboxylic acylcarnitine, C5-DC). Also the C5DC/C5-OH, C5DC/C8 and C5DC/C16 ratios have been found informative for GA I. This permits the earliest possible diagnosis and initiation of treatment for presymptomatic patients. In acutely ill patients, large amounts of glutaric acid can be detected in blood and urine by organic acid analysis. Analysis of the urine for abnormal organic acids in a suspected patient may reveal glutaric acid, 3-hydroxyglutaric acid (which is pathognomonic for GA I), and possibly glutaconic acid. These organic acids may be missing, however, in patients who are not acutely ill, in which case acylcarnitine analysis or enzymatic testing is preferred. GCD enzyme activity can be assayed in cultured fibroblasts, cultured amniocytes and chorionic villus (direct or cultured). Prenatal diagnosis has also been accomplished by finding elevated glutaric acid in amniotic fluid. DNA mutation analysis for prenatal diagnosis requires knowing the mutation(s) in the parents prior to testing. Free carnitine levels are often low and acylated carnitine levels are high at diagnosis. Plasma amino acids are usually normal and not helpful in diagnosis.
Early, aggressive treatment prior to onset of clinical symptoms may prevent development of neurological damage. At the onset of any sickness or metabolic decompensation, prompt, vigorous initiation of IV fluids, including glucose and carnitine, with monitored administration of insulin, is recommended. Restriction of protein, i.e. Lysine and Tryptophan restriction, has not produced clear clinical benefits.
This disorder most often follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder.