Myhre A G, Halonen M, Eskelin P, Ekwall O, Hedstrand H, Rorsman F, Kämpe O, Husebye E S
Division of Endocrinology, Institute of Medicine, Haukeland University Hospital, Bergen, Norway.
Clin Endocrinol (Oxf). 2001 Feb;54(2):211-7. doi: 10.1046/j.1365-2265.2001.01201.x.
The aim of the present study was to investigate Norwegian patients with autoimmune polyendocrine syndrome type I (APS I), with respect to occurrence and clinical presentation, reactivity towards different autoantigenes and mutations in the autoimmune regulator (AIRE) gene.
Twenty Norwegian patients from 15 families with APS I (11 males, nine females; mean age 26 years, range 4--54) were included by contacting all major hospitals in Norway.
Clinical data was collected from both patients and their physicians by the use of questionnaires and patient records. Autoantibodies were analysed using radioimmunoassays based on antigen synthesized by in vitro transcription and translation. AIRE mutations were determined by DNA sequence analysis.
The prevalence of APS I in Norway was estimated to be about 1 : 80,000 individuals. We found about the same distribution of disease characteristics as has been reported in Finnish patients. The diagnosis was delayed in many individuals. In two thirds of the cases, the patients were admitted in Hospital with acute adrenal insufficiency or hypocalcaemic crisis. Forty percent of these patients already had one of the main disease manifestations. Four different mutations in the AIRE gene were found in the Norwegian cohort. A 13-bp deletion in exon 8 (1085--1097(del)) was the most frequent mutation, present in 22/40 (55%) of the alleles. Eighty-five percent of the patients had either autoantibodies against 21 hydroxylase or aromatic L-amino acid decarboxylase. Five of eight women (age > 13 years) had ovarian failure, and all of these had antibodies against side-chain cleavage enzyme (P = 0.0002).
Norwegian patients with APS I clinically resemble patients from Finland and other European countries. The diagnosis APS I must be considered in children and adolescents with chronic mucocutaneous candidiasis, autoimmune adrenocortical failure or hypoparathyroidism in order to avoid fatal complications. Analysis of autoantibodies and mutational analysis of the AIRE gene are valuable diagnostic tools, especially in the early stages of the disease.
本研究旨在调查挪威的自身免疫性多内分泌腺综合征I型（APS I）患者，包括其发病情况和临床表现、对不同自身抗原的反应性以及自身免疫调节因子（AIRE）基因的突变情况。
通过联系挪威所有主要医院，纳入了来自15个家庭的20例挪威APS I患者（11例男性，9例女性；平均年龄26岁，范围4 - 54岁）。
通过问卷调查和患者记录收集患者及其医生的临床数据。使用基于体外转录和翻译合成抗原的放射免疫分析法分析自身抗体。通过DNA序列分析确定AIRE基因突变。
据估计，挪威APS I的患病率约为1 : 80,000。我们发现疾病特征的分布与芬兰患者的报道大致相同。许多患者的诊断被延迟。在三分之二的病例中，患者因急性肾上腺功能不全或低钙血症危象入院。这些患者中有40%已经出现了主要疾病表现之一。在挪威队列中发现了AIRE基因的四种不同突变。外显子8中的13 bp缺失（1085 - 1097(del)）是最常见的突变，存在于40个等位基因中的22个（55%）。85%的患者有抗21羟化酶或芳香族L - 氨基酸脱羧酶的自身抗体。8名年龄大于13岁的女性中有5名出现卵巢功能衰竭，且所有这些女性都有抗侧链裂解酶抗体（P = 0.0002）。
挪威的APS I患者在临床上与芬兰及其他欧洲国家的患者相似。对于患有慢性黏膜皮肤念珠菌病、自身免疫性肾上腺皮质功能衰竭或甲状旁腺功能减退的儿童和青少年，必须考虑诊断APS I，以避免致命并发症。自身抗体分析和AIRE基因突变分析是有价值的诊断工具，尤其是在疾病早期。
