Importance of Monitoring Glutathione Level as a Marker for Oxidative Stress in Urea Cycle Disorders

Ketki V Kudalkar, Anil B Jalan, Debjani Dasgupta

Abstract

Background: Oxidative stress (OS) is a major factor affecting pathogenicity in various inborn errors of metabolism. There is a possible role of free radical generation in the pathophysiology of neurodegenerative disorders, including some urea cycle disorders (UCDs).

Aim: To analyze the reduced level of blood glutathione (GSH) in neonates with UCDs as a parameter to monitor the effect of OS in them

Materials and Methods: The GSH level was analyzed in 24 neonates with UCDs: 1 neonate with carbamoyl phosphate synthetase deficiency (CPSD)/N-acetylglutamate synthetase deficiency (NAGSD), 4 with ornithine transcarbamylase deficiency (OTCD), 15 with argininosuccinate synthetase deficiency (ASSD), 3 with argininosuccinate lyase deficiency (ASLD), and 1 with arginase deficiency (ARGD).

Results and Discussion: This study demonstrated a lower level of GSH in neonates with UCDs (24.28 ± 14.97 nmol/mg Hb; n = 24) compared with normal controls (46.64 ± 17.51 nmol/mg Hb; n = 54). A considerably lower level of GSH was observed in neonates with CPSD/NAGSD (19.61 nmol/mg Hb; n = 1), OTCD (22.15 ± 6.59 nmol/mg Hb; n = 4), ASSD (24.42 ± 14.98 nmol/mg Hb; n = 15), and ASLD (24.11 ± 3.91 nmol/mg Hb; n = 3). The GSH level in a neonate with ARGD was comparable to that in the controls (33.91 nmol/mg Hb). Neonates who succumbed in the neonatal period had a lower level of GSH compared with others in the same group (16.24 ± 13.33 nmol/mg Hb; n = 11), indicating that antioxidant mechanisms could be severely impaired in critically ill patients. The GSH level was found to vary inversely with ammonia level in a neonate with ASSD (P < .01). There was a significant improvement in GSH level upon controlling the ammonia level.

Conclusion: Patients with UCDs have a considerably reduced level of GSH, indicating increased OS. Thus, estimation of the reduced GSH level in these patients may serve as a useful indicator of their OS.

UCDs are associated with increased OS, and it may be associated with the neurologic outcomes; hence, OS should be monitored, and thermapies that improve the redox imbalance may help in improving the outcome of these patients.

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