Clinical and immunological characteristics of five patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in China-expanding the atypical phenotypes.

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulatory system caused by forkhead box P3 (FOXP3) mutations. Abnormal numbers or functions of regulatory T (Treg) cells account for the various autoimmune symptoms. We aimed to explore the molecular genetics and phenotypic spectra of patients with atypical IPEX syndrome in China. Methods: We analyzed the molecular, clinical and immune phenotype characteristics of five Chinese patients with FOXP3 mutations. Results: We summarized the molecular and phenotypic features of five patients with FOXP3 mutations, including two novel mutations. Four of the five patients displayed atypical phenotypes, and one developed immune-related peripheral neuropathy. Three of the five patients showed normal frequencies of Treg cells, but the proportions of subsets of Treg cells, CD4+ T cells and B cells were out of balance. Conclusions: Our report broadens the understanding of the clinical features of atypical IPEX syndrome. Our detailed analyses of the immunological characteristics of these patients enhance the understanding of the possible mechanisms underlying the clinical manifestations.

Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessively inherited disorder characterized by variable combinations of endocrine and nonendocrine symptoms. In this report, we describe two 20- and 17-year-old Turkish siblings presenting with typical symptoms of APECED, including Addison disease, alopecia, vitiligo, and hypopituitarism, in whom electrocardiographic examinations demonstrated an abnormal prolongation of the QT interval. In both cases, excessive hypocalcemia due to primary hypoparathyroidism was identified as the underlying cause of the long QT syndrome. Sequencing the gene coding for the autoimmune regulator revealed a homozygous missense mutation in exon 14 with a C-to-T transition that resulted in the substitution of proline 539 for leucine in the carboxy-terminal protein molecule. Our data show that a single point mutation in the transcriptional active autoimmune regulator protein is associated with inherited alterations in calcium metabolism resulting from autoimmune reactions against the parathyroid glands. This finding defines a congenital autoimmune disease as a hereditary long QT syndrome.