Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED): single-centre experience

Background: APECED is a rare autosomal recessive disease, caused by mutations in the AIRE-gene resulting in a failure of T-cell tolerance, clinically characterized by multiple autoimmunopathies. The objective of the study was to determine the clinical and genetic features and consequences of APECED in a single-centre Ukrainian cohort of patients. Material and methods: Out of five families, eight patients with APECED were included in the study. Family history and clinical information of each patient was collected; laboratory studies aimed at identifying endocrine disorders, other autoimmunity, and infections was done. Genetic testing by NGS was performed in four out of five families. Patients were included in the study after the written informed consent had been signed by their parents/legal guardians. Results: In most patients, the onset of the disease was noted in childhood with manifestations of hypoparathyroidism and/or candidiasis. Adrenal insufficiency was associated later. Diabetes mellitus, hypothyroidism and hypogonadism were observed as other endocrinopathies. Five of eight patients (62.5%) developed autoimmune hepatitis, two patients suffered from autoimmune lung lesions, and two developed enteropathy. Two patients were diagnosed with brain damage: psychosis and autoimmune encephalitis. All the patients that we examined were homozygous carriers of the Finn major mutation R257X (c.769C> T) of the AIRE gene. Conclusions: One or two endocrinopathies in combination with recurrent candidiasis are the key to a diagnosis of APECED. Most patients also develop organ autoimmunopathy. The mutation R257X (c.769C> T) of the AIRE-gene is predominant in the population of western Ukraine.