21 investigation of coenzyme NADPH deficiency in congenital adrenal hyperplasia (KAH) due to hydroxylase deficiency

Deficiency of 21-hydroxylase enzyme expressed by the CYP21A2 gene is seen in 95% of cases of congenital adrenal hyperplasia. Since the pathophysiology of CAD is related to the degree of 21-hydroxylase enzyme deficiency, it results in clinical pictures ranging from insufficiency of aldosterone synthesis to insufficiency in the synthesis of sex steroids. The cytochrome P450 oxidoreductase enzyme (POR, CPR; EC 1.6.2.4) provides electrons to metabolic reactions catalyzed by cytochrome P450s in the endoplasmic reticulum. Since POR is an electron donor for the enzyme CYP21A2, steroid synthesis is irregular in POR deficiency. 21-hydroxylase activity expressed by CYP21A2 gene is decreased in POR mutant individuals. In our study, we aimed to investigate whether there is a relationship between POR enzyme and 21 hydroxylase enzyme activity in children diagnosed with CAD. There has not been any study examining the effect of POR enzyme on CYP21A2 enzyme activity in our country, it is important in terms of creating a database in genetic studies. A total of 54 individuals, aged between 0-18 years and 37 patients aged 0-18 years, who were diagnosed with congenital 21α-hydroxylase enzyme deficiency due to CYP21A2 gene mutation after genetic and biochemical tests, who applied to Gaziantep University Faculty of Medicine, Pediatric Endocrine and Metabolism Polyclinic, were included in our study. NADPH reductase enzyme activity in patient and healthy serum samples was measured with ELISA (Enzyme-linked immunosorbent assay) kit. The enzyme concentrations of the patient and control groups showed statistically significant differences (p<0.05). The enzyme concentration level of the patients is lower than the control group. While determining the cut-off point for the enzyme concentration, ROC analysis was used and the cut-off point was determined as 0.41 (p<0.05; AUC=0.679; Sensitivity= 51.35% (95% CI 34.4-68.1); Specificity=93 .75% (95% CI 69.8-99.8). Mutations in the cytochrome P450 reductase enzyme will also have an effect on the CYP21A2 gene mutation, as they will cause disorders in steroid synthesis. POR mutation should also be evaluated in CAH patients with CYP21A2 gene mutation. Studies to be conducted by increasing the number of patients may show the clinical importance of this association.