The autoimmune polyglandular syndromes (APS) are characterized by variable combinations of autoimmune endocrine diseases, such as Addison disease, hypoparathyroidism, and type 1 diabetes (T1D). Three types of APS have been distinguished (Table 1). These include the rare type 1 (APS1, OMIM 240,300), the more common type 2 (Schmidt's complex, 269,200) and type 3 APS [
- Neufeld M.
- Maclaren N.
- Blizzard R.
Autoimmune polyglandular syndromes.
Pediatr Ann. 1980; 9: 154-162
2]. APS1 also is known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients who have APS1 usually present with at least two of these diseases: Addison disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. In patients who have APS1, Addison disease predominantly begins in childhood or early adulthood. It is associated frequently with chronic active hepatitis, malabsorption, juvenile-onset pernicious anemia, alopecia, and primary hypogonadism. T1D or autoimmune thyroid disease are infrequent. Patients who have APS2 present with Addison disease and autoimmune thyroid disease or T1D, but do not have hypoparathyroidism or candidiasis. APS2 is not confined to one age group or sex; it is predominant in middle-aged women. The autoimmune disorders that occur with APS1, such as chronic active hepatitis, are rare in APS2, except for a low frequency of gonadal failure. Addison disease probably has a different genetic basis in APS1 than in APS2. The third type of APS, APS3, is represented by patients who have autoimmune thyroid disease and one or more other autoimmune disorders but do not have Addison disease. This article focuses on the mutation analysis in patients who have APS1 and the functional analyses of the autoimmune regulator (AIRE) protein.
- Ahonen P.
- Myllarniemi S.
- Sipila I.
- Perheentupa J.
Clinical variation of autoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy (APECED) in a series of 68 patients.
N Engl J Med. 1990; 322: 1829-1836
Table 1Component diseases and their frequencies in autoimmune polyglandular syndromes
|Addison disease||70% (early)||100% (late)||0%|
|Insulin-dependent diabetes mellitus||2–5%||52%||∀|
|Pernicious anemia||15% (early)||1% (late)||++|
|Chronic active hepatitis||11%||0%||0%|
|Squamous cell carcinoma, septicemia||++||+||−|
|HLA association||None||DR, DQ||?|
The exact frequencies for some component diseases are unknown but are estimated based on our clinical observation: ++ very common, + common, ∀ occasional presence, − absence.
Abbreviations: DR, HLA-DR; DQ, HLA-DQ.
Data from Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann 1980;9(4):154–62 and Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990;322(26):1829–36.
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