A non-classical presentation of APECED in a family with heterozygous R203X AIRE gene mutation

Biallelic loss-of-function mutations of AIRE cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome. However, single nucleotide mutations may cause a milder phenotype. In this paper, we describe an unusual and mild phenotype in a mother and her two children (son and daughter) who carry a rare heterozygous mutation of AIRE.

The son presented with alopecia and subclinical hypothyroidism due to Hashimoto's Thyroiditis (HT); the daughter had alopecia, vaginal mycosis, stomach pains and subclinical hypothyroidism due to HT; and the mother had alopecia, vaginal mycosis and stomach pains. Organ- and non-organ-specific autoantibodies were evaluated as well as antibodies against interleukin-17A, -17F, -22 (IL-Abs) and interferon -α and -ω (IFN-Abs). The organ- and non-organ-specific autoantibodies screening was negative in the son, while the daughter was positive for liver-kidney microsomal antibodies (LKMAbs) and the mother was positive for glutamic acid decarboxylase antibodies (GADAbs). Daughter and mother were also positive for IFN-Abs. Analysis of the AIRE gene identified a rare heterozygous R203X mutation in all three family members.

We describe for a first time a family with heterozygous R203X AIRE mutation causing an APECED-like condition, as confirmed by presence of IFN-Abs. The unusual mild phenotype should be reassuring for the patients and assist in their clinical management.