Deficiency in glutathion-synthetase

[MIM 231 900 ; 266 130]

(pyroglutamic aciduria )

Very rare. Mutation of the GSS gene is located on 20q11.2. Glutathione is synthesized in the cycle of the γ-glutamyles from glutamate, cysteine and glycine. The total absence of glutathione is lethal; multiple clinical presentations have been described:

-         generalized form with neurological damage (severe deficit): hemolytic anemia with metabolic acidosis  and 5-oxo-prolinuria, mental retardation, ataxia, spasticity and seizures.

-         generalized form without neurological impairment (moderate deficit): hemolytic anemia with 5-oxo-prolinuria and metabolic acidosis.

-         erythrocytic form (moderate impairment): chronic hemolytic anemia.


Currently, the term 'mild form' is used when the mutation causes an instability of the enzyme, and the term 'moderate and severe form' when the catalytic activity of the enzyme is impaired and diminished.


Symptomatic treatment: NaHCO3 (10 mmol/kg/day), vitamin E (10 mg/kg/day) and vitamin C (100 mg/kg/day). Avoid N-acetyl-cysteine because these patients already have high levels of cysteine.


Anesthetic implications: 

continue the regular symptomatic treatment (vitamins, NaHCO3); check hemoglobin levels; avoid drugs that produce hemolysis in case of  deficiency in glucose-6-phosphate dehydrogenase (see this term); be cautious with paracetamol.


References : 


Updated: September 2019