Autoimmune polyendocrine syndrome type 1

Autoimmune polyendocrine syndrome type 1
Classification and external resources
ICD-10	E 31.0
ICD-9	258.1
OMIM	240300
DiseasesDB	29212
eMedicine	med/1867
MeSH	D016884

Autoimmune polyendocrine syndrome type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), or Whitaker syndrome,^[1] is a form of autoimmune polyendocrine syndrome.

Autoimmune polyendocrine syndrome, type 1 is also known as candidiasis-hypoparathyroidism-Addison's disease-syndrome, Autoimmune Polyglandular Syndrome I,^[2] APECED, or APS-I. Its main features include:

A mild immune deficiency, leading to persistent mucosal and cutaneous infections with candida yeasts. There is also decreased function of the spleen (asplenism).
Autoimmune dysfunction of the parathyroid gland (leading to hypocalcaemia) and the adrenal gland (Addison's disease: hypoglycemia, hypotension and severe reactions in disease).
Other disease associations are:
- hypothyroidism
- hypogonadism and infertility
- vitiligo (depigmentation of the skin)
- alopecia (baldness)
- malabsorption
- pernicious anemia
- chronic active (autoimmune) hepatitis

As opposed to type 2, this syndrome inherits in an autosomal recessive fashion and is due to a defect in the autoimmune regulator (AIRE)^[3] a gene located on the 21st chromosome. The normal function of AIRE, a transcription factor, is to confer immune tolerance for antigens from endocrine organs by upregulating expression of those antigens in the medulla of the thymus, and promoting apoptosis of autoreacting T cells.

References

^ "Polyglandular Autoimmune Syndrome, Type I - eMedicine Endocrinology". Medscape. http://emedicine.medscape.com/article/124183-overview. Retrieved 2009-04-17.
^ Greenspan, Francis S.; Gardner, David C. (2004). Basic clinical endocrinology. New York: McGraw-Hill. pp. 103. ISBN 0-07-140297-7.
^ Bensing S, Fetissov SO, Mulder J, et al (January 2007). "Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1". Proc. Natl. Acad. Sci. U.S.A. 104 (3): 949–54. doi:10.1073/pnas.0610070104. PMC 1783420. PMID 17215373. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1783420. Retrieved 2008-07-25.

External links

EurAPS, a EU-funded consortium doing translational research on this condition

Endocrine pathology: endocrine diseases (E00–E35, 240–259)

Pancreas/
glucose
metabolism

Hypofunction	Diabetes mellitus types: (type 1, type 2, MODY 1 2 3 4 5 6) · complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy) insulin receptor (Rabson–Mendenhall syndrome) · Insulin resistance

Hyperfunction	Hypoglycemia · beta cell (Hyperinsulinism) · G cell (Zollinger–Ellison syndrome)

Hypothalamic/
pituitary axes

Hypothalamus

gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) · CRH (Tertiary adrenal insufficiency) · vasopressin (Neurogenic diabetes insipidus) · general (Hypothalamic hamartoma)

Pituitary

Hyperpituitarism	anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) · posterior (SIADH) · general (Nelson's syndrome)

Hypopituitarism	anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency) · posterior (Neurogenic diabetes insipidus) · general (Empty sella syndrome, Pituitary apoplexy, Sheehan's syndrome, Lymphocytic hypophysitis)

Thyroid

Hypothyroidism	Iodine deficiency · Cretinism (Congenital hypothyroidism) · Myxedema · Euthyroid sick syndrome

Hyperthyroidism	Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) · Hashitoxicosis · Thyrotoxicosis factitia · Graves' disease

Thyroiditis	Acute infectious · Subacute (De Quervain's, Subacute lymphocytic) · Autoimmune/chronic (Hashimoto's, Postpartum, Riedel's)

Goitre	Endemic goitre · Toxic nodular goitre · Toxic multinodular goiter Thyroid nodule

Parathyroid

Hypoparathyroidism	Pseudohypoparathyroidism

Hyperparathyroidism	Primary · Secondary · Tertiary · Osteitis fibrosa cystica

Adrenal

Hyperfunction	aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) · AME · Liddle's syndrome · 17α CAH cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome) sex hormones: 21α CAH · 11β CAH

Hypofunction/ Adrenal insufficiency (Addison's, WF)	aldosterone: Hypoaldosteronism (21α CAH, 11β CAH) cortisol: CAH (Lipoid, 3β, 11β, 17α, 21α) sex hormones: 17α CAH

Gonads

ovarian: Polycystic ovary syndrome · Premature ovarian failure

testicular: enzymatic (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) · Androgen receptor (Androgen insensitivity syndrome)

general: Hypogonadism (Delayed puberty) · Hypergonadism (Precocious puberty)

Height

Gigantism · Dwarfism/Short stature (Laron syndrome, Psychosocial)

Multiple

Autoimmune polyendocrine syndrome (APS1, APS2) · Carcinoid syndrome · Multiple endocrine neoplasia (1, 2A, 2B) · Progeria (Werner syndrome, Acrogeria, Metageria) · Woodhouse-Sakati syndrome

M: END

anat/phys/devp/horm

noco(d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

Immune disorders: hypersensitivity and autoimmune diseases (279.5–6)

Type I/allergy/atopy
(IgE)

Foreign	Atopic dermatitis · Allergic urticaria · Hay fever · Allergic asthma · Anaphylaxis · Food allergy (Milk, Egg, Peanut, Tree nut, Seafood, Soy, Wheat), Penicillin allergy

Autoimmune	none

Type II/ADCC
(IgM, IgG)

Foreign

Pernicious anemia · Hemolytic disease of the newborn

Autoimmune

Cytotoxic	Autoimmune hemolytic anemia · Idiopathic thrombocytopenic purpura · Bullous pemphigoid · Pemphigus vulgaris · Rheumatic fever · Goodpasture's syndrome

"Type 5"/receptor	Graves' disease · Myasthenia gravis

Type III
(Immune complex)

Foreign	Henoch–Schönlein purpura · Hypersensitivity vasculitis · Reactive arthritis · Farmer's lung · Post-streptococcal glomerulonephritis · Serum sickness · Arthus reaction

Autoimmune	Systemic lupus erythematosus · Subacute bacterial endocarditis · Rheumatoid arthritis

Type IV/cell-mediated
(T-cells)

Foreign	Allergic contact dermatitis · Mantoux test

Autoimmune	Diabetes mellitus type 1 · Hashimoto's thyroiditis · Guillain–Barré syndrome · Multiple sclerosis · Coeliac disease · Giant-cell arteritis

GVHD	Transfusion-associated graft versus host disease

Unknown/
multiple

Foreign	Hypersensitivity pneumonitis (Allergic bronchopulmonary aspergillosis) · Transplant rejection · Latex allergy (I+IV)

Autoimmune	Sjögren's syndrome · Autoimmune hepatitis · Autoimmune polyendocrine syndrome (APS1, APS2) · Autoimmune adrenalitis · Systemic autoimmune disease

M: LMC

cell/phys/auag/auab/comp, igrc

imdf/ipig/hyps/tumr

proc, drug(L3/4)

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains	1.2: Feingold syndrome · Saethre-Chotzen syndrome 1.3: Tietz syndrome

(2) Zinc finger DNA-binding domains	2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis 2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome 2.3: Greig cephalopolysyndactyly syndrome/Pallister-Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 2 2.5: Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains	3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat-Wilson syndrome) 3.2: PAX2 (Papillorenal syndrome) · PAX3 (Waardenburg syndrome 1&3) · PAX4 (MODY 9) · PAX6 (Gillespie syndrome, Coloboma of optic nerve) · PAX8 (Congenital hypothyroidism 2) · PAX9 (STHAG3) 3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX) 3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome)

(4) β-Scaffold factors with minor groove contacts	4.2: Hyperimmunoglobulin E syndrome 4.3: Holt-Oram syndrome · Li-Fraumeni syndrome · Ulnar–mammary syndrome 4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7) · SOX10 (Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome) 4.11: Cleidocranial dysostosis

(0) Other transcription factors	0.6: Kabuki syndrome

Ungrouped	TCF4 (Pitt-Hopkins syndrome) · ZFP57 (TNDM1) · TP63 (Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8)

Transcription coregulators	coactivator: CREBBP (Rubinstein–Taybi syndrome) corepressor: HR (Atrichia with papular lesions)

see also transcription factors B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk