The evaluation of thiol-disulfide homeostasis in children with Triple-A syndrome.

Abstract

Triple-A syndrome occurs due to the dysfunction of the ALADIN protein as a result of a mutation in the AAAS gene. ALADIN is involved in redox homeostasis in human adrenal cells and steroidogenesis. It has also been shown to have important roles in DNA repair and the protection of cells against oxidative stress. We planned to investigate serum thiol/disulfide homeostasis, which is a part of redox hemostasis in patients with Triple-A syndrome. The study included patients with the Triple-A syndrome (26 patients) and healthy children (26 patients). Thiol and disulfide levels of patients and healthy groups were compared. In addition, patients with the Triple-A syndrome were divided into 2 subgroups according to the mutation type, and their thiol and disulfide levels were compared. Triple-A syndrome patients had increased native thiol (SH), total thiol (SH+SS) concentrations, and native thiol/total thiol (SH/SH+SS) ratios than healthy controls. However, Triple-A syndrome patients had lowered disulfide (SS), disulfide/native thiol (SS/SH), and disulfide/total thiol (SS/SH+SS) ratios than the controls. When the group with the p.R478* mutation and the group with other mutation were compared, disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio were statistically higher in the group with the p.R478* mutation, while native thiol/total thiol ratio was found to be lower. However, no statistical difference was found between native thiol and total thiol levels. This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with the Triple-A syndrome. Patients with Triple-A syndrome had an increased level of thiol compared with healthy controls. Comprehensive studies are needed to clarify these thiol levels, which are thought to be compensatory. Also, mutation type affects thiol-disulfide levels.