5-Oxoprolinuria is a biochemical finding that can arise from two underlying metabolic disorders. It is characterized by excretion of massive amounts of the chemical 5-oxoproline.
5-Oxoprolinuria is characterized by excretion of massive amounts of 5-oxoproline (pyroglutamic acid) in the urine, and abnormally high levels of this acid in the blood and cerebrospinal fluid. Without treatment, mental retardation, impaired muscle coordination (cerebellar ataxia), and seizures may occur.
This finding can result from generalized glutathionine synthetase deficiency or 5-oxoprolinase deficiency. It has also been reported where there is no enzyme defect in the gamma-glutamyl cycle in patients with severe burns or Stevens-Johnson syndrome.
Glutathionine Synthetase Deficiency
Glutathionine synthetase deficiency is a metabolic disorder characterized by excretion of the chemical 5-oxoproline in the urine, metabolic acidosis and increased rate of red cell hemolysis (premature breakdown of red blood cells). Some affected individuals also have central nervous system problems such as learning disability, seizures, poor balance and weakness of the limbs.
5-oxoprolinase deficiency also causes excretion of the chemical 5-oxoproline in the urine. There is no accompanying metabolic acidosis or hemolysis. Since there are only a few known cases the full clinical picture is as yet unknown.
5-Oxoprolinuria is inherited as an autosomal recessive trait. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Glutathionine synthetase deficiency is treated with sodium bicarbonate to correct the metabolic acidosis. Vitamins E and C may also be given. Drugs that precipitate hemolysis should be avoided. There are no standard therapies for 5-oxoprolinase deficiency.
Glutathionine synthetase and 5-oxoprolinase deficiencies are inherited as autosomal recessive traits.
Genetic counseling should be offered to families in whom an inborn error of the gamma-glutamyl cycle is found.
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