National Organization for Rare Disorders, Inc.

Skip to the navigation


It is possible that the main title of the report 5-Oxoprolinuria is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Pyroglutamic Aciduria
  • Pyroglutamicaciduria

Disorder Subdivisions

  • None

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.

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:




Larsson A, Anderson ME. Glutathione synthetase deficiency and other diseases of the glutamyl cycle. In: Scriver RS, AL Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001: 2205-2216.

Shi ZZ, Habib GM, Lieberman MW. Glutathione synthetase deficiency (5-oxoprolinuria). In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. In Press


Ristoff E, Mayatepek E, Larsson A. Long-term clinical outcome in patient with glutathione synthetase deficiency. J Pediatr. 2001;139:79-84.

Corrons JL, Alvarez R, Pujades A, et al. Hereditary non-spherocytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain. Clinical and molecular studies. Br J Haematol. 2001;112:475-82.

Al-Jishi E, Meyer BF, Rashed MS, et al. Clinical, biochemical, and molecular characterization of patients with glutathione synthetase deficiency. Clin Genet. 1999;55:444-49.

Mayatepek E. 5-Oxoprolinuria in patients with and without defects in the gamma-glutamyl cycle. Eur J Pediatr. 1999;158:221-25.

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.


CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk

The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org

NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.