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Synonyms of 5-Oxoprolinuria

Disorder Subdivisions

General Discussion

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
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.

Affected Populations

The conditions are present at birth. They are extremely rare disorders.

Related Disorders

Symptoms of the following disorders may be similar to those of 5-Oxoprolinuria. Comparisons may be useful for a differential diagnosis:

5-Oxoprolinase Deficiency is another congenital disorder due to enzyme deficiency: in this case, a deficiency of the enzyme 5-oxoprolinase. A moderate amount of 5-oxoproline is excreted in the urine and blood levels of this substance are higher than normal. This disorder is benign and those afflicted usually exhibit no other symptoms.

Glutathionuria (Gamma-Glutamyl Transpeptidase Deficiency) is another, even more, rare enzyme-deficiency disorder. Concentrations of glutathione in blood and urine are excessive. Patients with this disorder may be mildly mentally retarded and/or suffer from behavioral problems.

Standard Therapies

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.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

5-Oxoprolinuria Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Polekhina G, Board PG, Gali RR, et al. Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. EMBO J. 1999;18:3204-3213.

Dahl N, Pigg M, Ristoff E, et al. Missense mutations in the human glutathione synthetase gene result in severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and neurological misfunction. Hum Mol Genet. 1997;6:1147-1152.

Shi ZZ, Habib GM, Rhead WJ, Gahl WA, He X, Sazer S, Lieberman MW. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat Genet. 1996; 13:361-365.

Jain A, et al. Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glatathione synthetase deficiency. J Pediatr.1994;124:229-33.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 266130; Last Update: 10/4/2001. Entry No: 601002; Last Update: 4/17/2002. Entry No: 231900; Last Update: 10/4/2001. Entry No: 260005; Last Update: 4/172002.

Report last updated: 2008/05/23 00:00:00 GMT+0