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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia.

BACKGROUND: Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities. METHODS AND RESULTS: We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%). CONCLUSIONS: Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

Cushing's syndrome caused by use of synthetic ocular steroid.

WHAT IS KNOWN AND OBJECTIVE: Cases of Cushing's syndrome (CS) following ocular steroid use have been reported in recent years, albeit rarely. CASE DESCRIPTION: We report a case of iatrogenic CS in a child induced by fluorometholone-containing eyedrops. Our patient was referred to our endocrinology clinic due to rapid weight gain. His history revealed that 1.5 months previously he had been started on fluorometholone eyedrops. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, no cases of CS have been reported following ocular fluorometholone use. Although eyedrops containing potent glucocorticoids may lead to CS, fluorometholone, a relatively less potent steroid, may also cause the syndrome, as in our case.