Glutathione synthetase deficiency is a rare autosomal recessive disorder characterized by excessive accumulation of 5-oxoproline. Oxoprolinuria can be due to deficiency of either glutathione synthetase (GSS) or 5 oxoprolinase enzymes. The two forms can be distinguished from each other by the absence of hemolytic anemia in the latter. The GSS deficient form of oxoprolinuria can range from mild to severe, and is characterized by metabolic acidosis, hemolytic anemia, psychomotor and mental retardation, seizures, ataxia, and spasticity. The milder form of GS deficiency is limited to erythrocytes, resulting in chronic hemolytic anemia and neonatal jaundice; while the more severe form is what leads to 5-oxoprolinuria and metabolic acidosis. Recurrent bacterial infections are also common.
A diagnosis of pyroglutamic aciduria is made based on the low activity of glutathione synthetase enzyme in cultured skin fibroblasts, low glutathione levels in RBCs, high urinary 5 oxoprolinuria level, as well as mutations in the GS gene. GC-MS is a useful technique for measuring the levels of the urinary metabolites. Prenatal diagnosis is also possible by way of amniotic fluid or chorionic villus sampling. Treatment aims at avoiding hemolytic crises and increasing the defense against reactive oxygen species. The prognosis differs significantly between patients.