Autoimmune polyglandular syndrome type 1 in siblings: assembling the jigsaw puzzle

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive, monogenic disease, that could be presented as a group of various symptoms, but clinical diagnosis requires existence of minimum two of three leading disorders: chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenocortical insufficiency. Case Presentation We report the clinical cases of two siblings with APS-1, one 28-year-old male and one 25-year-old female. He is presenting at the age of 3.5 years with Addison’s disease, as well as with hypoparathyroidism at the age of 4 years. Meanwhile, at the age of 4 years, onychomycosis, enamel dysplasia and diffuse alopecia were presented in the female, along with hypoparathyroidism. Furthermore, at the age
of 11 years, the diagnosis of Addison’s disease was made in the female, and at the age of 13.5 years Hashimoto’s thyroiditis was diagnosed. The onset of menarche was at the 14 years, but she further developed hypogonadism as a manifestation of the autoimmune oophoritis. Hormonal replacement therapy was initiated for both siblings, including hydrocortisone and fludrocortisone, as well as levothyroxine and levonorgestrel-ethynyl estradiol to the female. Because of hypoparathyroidism, alfacalcidol with calcium supplement were established for both siblings. Since hypercalciuria was confirmed with recurrences of deep hypocalcemia
episodes in the female, hydrochlorothiazide was also introduced into the therapy. Moreover, gastrointestinal endoscopy showed chronic atrophic pangastritis with active Helicobacter pylori (H. pylori) infection and chronic duodenitis, enteritis and colitis. H. pylori first-line eradication therapy was initiated. Values of fecal calprotectin, anti-transglutaminase antibodies IgA, fecal PMN-elastase and bile acids were unremarkable. Genetic testing detected a homozygous c.769COT (R257X (p.Arg257X)) AIRE mutation in both siblings. Conclusions
Although this is a rare disease, clinicians should be aware of it, especially in people under 30 years of age with more than one endocrine disorder, because timely diagnosis avoids its life-threatening conditions.