Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy: Insights into Genotype-Phenotype Correlation

Table 1

Main clinical features of APECED, specific related autoantibodies (when clearly associated with clinical manifestation) and usual period of life at onset of disease.

Clinical manifestation	Autoantibody specificities	Usual age at onset
Classic triad
(i) Candidiasis	IL-17F, IL-22 [9]	Childhood
(ii) Hypoparathyroidism	NALP5, CaSR [13–15]	Childhood
(iii) Adrenal failure	P450c17, P450c21, P450scc [4, 37, 42, 83]	Childhood and adolescence
Other endocrine disorders
(i) Ovarian failure	P450scc and P450c17 [4]	Adolescence to adulthood
(ii) Testicular failure	TSGA10 [84]	Adolescence to adulthood
(iii) Diabetes mellitus	IA-2, GAD65 [4, 42, 43]	Adulthood
(iv) Hypothyroidism	TG, TPO [38, 43]	Childhood to adulthood
(v) Hypopituitarism	TDRD6 [41]	Adolescence to adulthood
Ectodermal features
(i) Alopecia	TH, hair follicles [4, 85]	Childhood to adulthood
(ii) Vitiligo	Melanocyte, SOX9, SOX10, AADC [39]	Childhood to adulthood
(iii) Keratopathy	Unknown	Childhood and adolescence
(iv) Enamel dysplasia	Unknown	Childhood
(v) Rash with fever	Unknown	Childhood
Gastrointestinal disorders
(i) Gastritis/pernicious anemia	H^+/K^+ ATPase, IF [26, 43]	Childhood to adulthood
(ii) Severe obstipation	TPH, HDC [4, 23, 40]	Childhood to adulthood
(iii) Chronic diarrhea	TPH, HDC [4, 23, 40]	Childhood to adulthood
(iv) Immune Hepatitis	CYP1A2, CYP2AC, AADC, TPH, HDC [3, 4, 19–21]	Childhood
Lung manifestations	KCNRG [27]	Childhood to adulthood
Tubulointerstitial nephritis	Unknown	Childhood
Asplenia	Unknown	Childhood to adulthood

IL-17F: interleukin 17F, IL-22: interleukin 22, NALP5: NACHT leucine-rich-repeat protein 5, CaSR: calcium-sensing receptor, P450c17: Steroid 17-α-hydroxylase, P450c21: steroid 21-hydroxylase, P450scc: side-chain cleavage enzyme, TSGA10: testis-specific gene 10 protein, IA-2: islet antigen-2, GAD65: glutamic acid decarboxylase-65, Tg: thyroglobulin, TPO: thyroid peroxidase, TDRD6: tudor domain-containing protein 6, TH: tyrosine hydroxylase, AADC: aromatic l-amino acid decarboxylase, IF: intrinsic factor, TPH: tryptophan hydroxylase, HDC: histidine decarboxylase, CYP1A2: cytochrome P450 1A2, CYP2AC: cytochrome P450 2AC, KCNRG: potassium channel-regulating protein.