Glutathione Synethtase Deficiency​ - 5-oxoprolinemia

Glutathione synthetase deficiency also known as 5-oxoprolinuria, is an extremely rare disorder characterized by a deficiency of the enzyme glutathione synthetase. This enzyme is part of the chemical process by which the body creates glutathione, a protein molecule that plays a role in many cell processes. Glutathione synthetase deficiency is often classified as mild, moderate or severe. Consequently, the specific symptoms and severity can vary greatly from one person to another.

What else is it called?

  • 5-oxoprolinemia
  • 5-oxoprolinuria
  • Deficiency of glutathione synthase
  • Deficiency of glutathione synthetase
  • Pyroglutamic acidemia
  • Pyroglutamic aciduria

What causes it?

Glutathione synthetase deficiency was first described in the 1970’s as a rare autosomal recessive disorder in which the body cannot produce the molecule glutathione. Glutathione is an important molecule which neutralises unstable molecules that are produced through energy production, building DNA, essential proteins and other fundamental properties for the body.

Mutations in the inherited GGS gene causes this condition, this gene provides instructions for making the enzyme glutathione synthetase which can break down glutathione. With this disorder the body is unable to break down glutathione or may only be able to break it down in small quantities.

Glutathione synthetase deficiency falls into 3 subtypes; mild, moderate and severe. Mild glutathione synthetase deficiency usually leads to the destruction of red blood cells [haemolytic anaemia]. Individuals with the moderate version of this condition may experience symptoms. With the severe form of this condition, individuals may experience neurological dysfunctions.

How common is it?

This condition has been found in no more than 70 people worldwide, with no preference over males or females.

What are the signs and symtoms?

The signs and symptoms of this Disorder are dependent upon the subtype one may be diagnosed with. Some of the more common symptoms one may experience are:

  • Seizures
  • Anaemia
  • Intellectual disability
  • Failure to thrive
  • Fatigue
  • Pale skin color due to anaemia
  • Loss of coordination

How is it diagnosed?

A diagnosis for this condition may be considered when your child experiences metabolic acidosis. This is suggestive of a metabolic condition. A doctor may order a blood test which involves a sharp needle being placed into your arm to get a sample of blood to test for levels of glutathione or a urine test to test your urine for levels of this metabolite.

Can it be treated?

Unfortunately, there is no treatment for this condition, treatment generally relies upon the management of the symptoms experience for the specific subgroups of the condition. Treatment may therefore include doses of sodium bicarbonate to counteract the low levels of glutathione and supplementation of vitamins to interact with free radical damage within the body.

People diagnosed with this condition also require a lot of follow up appointments at their local doctors, pediatrician or hospital.

Do my family need to be tested?

Autosomal recessive disorder.

Glutathione synthetase deficiency 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 counselor. They can explain how you may have inherited Glutathione synthetase deficiency. 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.

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