Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease

作者：Magitta Ng'weina F; Pura Mikulas; Wolff Anette S Boe; Vanuga Peter; Meager Anthony; Knappskog Per M; Husebye Eystein S^*

来源：European Journal of Endocrinology, 2008, 158(5): 705-709.

DOI：10.1530/EJE-07-0843

Background: Autoimmune polyendocrine syndrome type 1 (APS I) is a monogenic disease affecting endocrine glands and other organs due to mutations of the autoimmune regulator (AIRE) gene. There is a wide variability in clinical phenotypes in patients with APS I, which makes the diagnosis a challenge.
Objective: To screen for APS I among Slovakian patients with sporadic Addison's disease and clinical features that raised the suspicion of APS I.
Methods: All 14 exons and exon-intron boundaries of the AIRE gene were sequenced. In addition, autoantibodies specific for Addison's disease and polyendocrine syndromes were assayed.
Results: Using clinical criteria we identified four patients with APS I in three families. Two patients had a novel missense mutation in exon 2 (c.274C>T, p.R92W) and either the Finnish major mutation (c.769C>T) or the common.1.3 bp deletion (c.967-979del13bp). APS I was diagnosed in a brother of the latter after his death due to an adrenal crisis. A fourth patient had primary adrenal failure and hypoparathyroidisrn without AIRE mutations or APS-I specific autoantibodies.
Conclusions: Four patients with APS I were found in a Slovakian cohort of Addison patients, although the lack of detectable AIRE mutations and APS I-specific autoantibodies raises uncertainty regarding the pathogenesis in one of the patients. This study demonstrates the merits of screening patients with phenotypic features or autoantibody findings that could indicate APS I. even in adult patients. It is necessary to identify APS I patients in order to provide appropriate treatment and follow-up of the various components of APS I.

• 出版日期2008-5
• 单位河北医科大学