Autoimmune polyglandular syndrome type 1 with compound heterozygous AIRE gene pathogenic variants and stage 1 type 1 diabetes mellitus: case report and literature review of Chinese population.

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disorder caused by pathogenic variants in the AIRE gene, characterized by impaired central immune tolerance and multi-organ autoimmune damage. While relatively common in genetically isolated populations, genetically confirmed APS-1 cases remain exceptionally rare in Chinese individuals. To date, population-specific genotypic and phenotypic features of APS-1 in China have not been systematically summarized.

CASE PRESENTATION: We report a 31-year-old female patient who presented with hypocalcemic convulsions as the initial symptom, accompanied by a 20-year history of vitiligo and mild anemia, newly developed chronic diarrhea and positive islet autoimmunity. Laboratory examinations confirmed hypoparathyroidism and stage 1 type 1 diabetes mellitus (T1DM) with significantly elevated islet autoantibodies but normal islet function. Genetic analysis identified novel compound heterozygous pathogenic variants in the AIRE gene: a missense variant c.977C>T (p.Pro326Leu) inherited from her mother and a 1.6 kb deletion spanning exons 2-4 with an untraceable origin due to the lack of paternal specimen, both classified as pathogenic according to ACMG guidelines.

CONCLUSION: We performed a systematic narrative review integrating 24 previously reported genetically confirmed Chinese APS-1 cases, forming a combined cohort of 25 cases for comprehensive analysis. This study identified the deletion of AIRE gene exons 2-4 as a recurrent pathogenic variant observed in Chinese APS-1 patients, and revealed distinct phenotypic patterns of Chinese patients including a male-to-female ratio of 2:1, a low incidence of the classic triad (44%) and a 16% prevalence of pancreatic autoimmunity. As the first genetically confirmed Chinese case of APS-1 complicated with stage 1 T1DM, this report fills the gap in early pancreatic autoimmunity phenotypic data for Chinese APS-1 patients and enriches the disease's clinical and genetic spectrum. Clinicians should suspect APS-1 and prioritize early AIRE gene testing in young patients with non-surgical hypoparathyroidism and concurrent autoimmune manifestations to prevent misdiagnosis or delayed diagnosis.