ESPE Abstracts (2019) 92 P1-248

A Novel AIRE Gene Mutation in Two Siblings Revealing Different Phenotypes of Autoimmune Polyendocrine Syndrome Type 1

Melek Yildiz1, Banu Aydin1, Alper Gezdirici2, Hasan Onal1


1Division of Pediatric Endocrinology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey. 2Division of Genetics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey


Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autoimmune disease characterized by chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Minor components of the disease are diverse among patients, even within the same family. APS-1 is autosomal recessively inherited and caused by biallelic mutations in the autoimmune regulator (AIRE) gene.

Objective and Hypotheses: To define different clinical and laboratory characteristics of two affected siblings diagnosed as APS-1 with the same genetic cause.

Method and Results: Case 1: A 3.7-year-old girl of consanguineous parentswas referred due to tetany. She was born with a birth weight of 3300 grams after an uneventful term pregnancy. Physical examination revealed a weight of 13.7 kg (SD score -0.98), height 95.2 cm (SD score -1.23) with normal systemic examination and prepubertal development. She was diagnosed with hypoparathyroidism due to hypocalcemia, hyperphosphatemia and low parathyroid hormone levels. During follow-up, she revealed dental enamel hypoplasia, fragile nails, malabsorptive symptoms and growth retardation. At the age of 12, she was diagnosed with growth hormone deficiency with normal MRI of hypophysis and normal 46,XX karyotype.

Case 2: A 4.2-year-old brother of the index patient presented with hypoparathyroidism. He was born with a birth weight of 3750 grams after an uneventful term pregnancy. Physical examination revealed a weight of 18 kg (SD score +0.35), height 104 cm (SD score -0.32) with normal vital signs and normal prepubertal development. During follow-up he revealed ectodermal dystrophy of the nails and total alopecia areata. Adrenal functions of the both patients were normal. Genetic analysis of AIRE gene in these two siblings revealed a novel homozygous mutation NM_000383.4:c.464-3C>G. The familial segregation was consistent with an autosomal recessive trait.

Conclusion: This is the first report of the mutation NM_000383.4:c.464-3C>G in AIRE gene, which resulted in different phenotypes of APS-1 in two siblings. Here we also report isolated growth hormone deficiency as an unusual finding of APS-1.

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