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.
The Centre for Arab Genomic Studies Work Group (2006) conducted a retrospective study for metabolic disorders described at AlWasl Hospital in Dubai between 1995 and 2004. Among 64 patients diagnosed, only one case of pyroglutamic aciduria occurred in a 13-day-old female from Egypt.
Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among the 82 patients, only one was diagnosed with pyroglutamic aciduria [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000].
[See: Egypt > CAGS Work Group, 2006].