Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis.

Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%-93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.

Age and Gender-Specific Reference Intervals for Uric Acid Level in Children Aged 5-14 Years in Southeast Zhejiang Province of China: Hyperuricemia in Children May Need Redefinition.

Context: Hyperuricemia is defined when the plasma uric acid concentration is above 416 µmol/L (7 mg/dl) in male adults, or 357 µmol/L (6 mg/dl) in female adults. However, there are no explicit criteria yet for children. Objective: It is necessary to set up reference intervals for the uric acid level in different age groups among children. Materials and Methods: A total of 5,439 individuals (3,258 males, 2,181 females) were included in the final statistical analysis. Reference values of all age groups were determined by statistical descriptions. Multiple linear regression analysis was applied to determine the relationship between uric acid level, BMI, and age. Results: The level of uric acid increased with age. Gender differences in uric acid level occurred after the onset of puberty. Additionally, linear regression revealed a positive correlation between the uric acid level and BMI. Discussion and Conclusion: The reference range of the uric acid level in children is inconsistent with the previous viewpoint. Body mass index plays an important role in uric acid metabolism.