What else is it called?

  • Glutathione synthetase deficiency
  • GSD
  • Pyroglutamic aciduria
  • 5-Oxoprolinuria

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What causes it?

Oxoprolinuria is a rare autosomal recessive condition caused by mutations to the GSS gene. The GSS gene contains instructions for making the enzyme glutathione synthetase. This enzyme is required for the body to create the small protein molecule glutathione. This is called a co-enzyme which is essential to many cellular functions including serving a key role in cellular protection from toxic substances. An alteration in the GSS gene leads to deficiency of glutathione synthetase, which, in turn, leads to a lack of glutathione.

5-oxoproline, a by-product of glutathione deficiency can accumulate in blood, urine and cerebrospinal fluid with harmful health consequences.  However, it is worth noting that 5-oxoprolinuria can occur as part of several different disorders or due to several environmental factors so diagnosis may rely upon further testing.

How common is it?

Oxoprolinuria affects males and females in equal numbers. More than 70 individuals from 50 families have been described in the medical literature. The exact incidence and prevalence are unknown. Because individuals may be misdiagnosed or go undiagnosed, determining the true frequency in the general population is difficult.

What are the signs and symptoms?

Clinically, there are two forms of Oxoprolinuria. The most severe form, generalized GSD, is expressed in multiple tissues, while the other, usually milder form, erythrocyte GSD, is expressed only in erythrocytes [red blood cells]. 

Generalized GSD

This results in reduced glutathione levels in erythrocytes, leukocytes, fibroblasts and other tissues. Symptoms, including:

  • metabolic acidosis
  •  hemolytic anemia,
  • Jaundice
  • Urinary excretion of large amounts of 5-oxoproline

These symptoms may be present within the first few days of life. Diagnosis is possible during the neonatal period. Infants with GSD are susceptible to severe metabolic decompensation shortly after birth and later in life during intercurrent illnesses. Without treatment, progressive neurological symptoms such as ataxia, spasticity and/or seizures may result from chronic metabolic acidosis. 

Erythrocyte GSD 

This results in reduced glutathione levels in erythrocytes, but not in other tissues. This reduction of glutathione levels may cause a mild form of hemolytic anemia and, occasionally, splenomegaly. Erythrocyte GSD does not usually result in urinary excretion of 5-oxoproline or metabolic and neurological complications.

Chronic and progressive disorders of vision known as retinal dystrophies have been reported in adults with glutathione synthetase deficiency.

How is it diagnosed?

In some countries, this condition is tested via newborn screening, it is worth checking if this is the case if you suspect or have previous family history of this condition.

This may also be determined by urine and blood analysis or by lumbar puncture for high levels of 5-oxoprolinuria. However, as previously stated this can be caused by other environmental factors so further testing along with expressing signs and symptoms of this condition would be required for accurate diagnosis.

Can it be treated?

Early diagnosis and prompt treatment are essential for an improved prognosis.  Individuals with GSD require prompt correction of any metabolic acidosis and/or hyperbilirubinemia [waste product of haemoglobin] to help prevent brain damage. Oral maintenance doses of sodium bicarbonate or citrate may help to correct chronic acidosis. Anemia may require blood transfusions and any electrolyte imbalances should be corrected.

Your infant/child should be admitted for medical care, including administration of intravenous therapies to prevent/treat metabolic acidosis and/or electrolyte imbalances.

Do my family need to be tested?

Oxoprolinuria can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inheritedOxoprolinuria. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

If you have previously had a child with Oxoprolinuria and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.

Relevant Organisations


References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002].

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