Details of Disease

General Information of Disease (ID: DISWJP8J)

• Disease Name: Autoimmune polyendocrine syndrome type 1
• Synonyms: polyglandular deficiency syndrome, Persian-Jewish type; PGA 1; hypoadrenocorticism with hypoparathyroidism and superficial Moniliasis; autoimmune polyendocrinopathy syndrome, type I, autosomal dominant; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED); APS 1; autoimmune polyglandular syndrome, type 1; autoimmune polyendocrinopathy type 1; polyglandular autoimmune syndrome, type 1; autoimmune polyendocrinopathy syndrome type 1; Whitaker syndrome; autoimmune polyendocrine syndrome, type I, with or without reversible metaphyseal dysplasia; autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia; APECED syndrome; MEDAC syndrome; autoimmune polyglandular syndrome type 1; autoimmune polyglandular syndrome I; polyglandular autoimmune syndrome type 1; hypoparathyroidism-Addison disease-mucocutaneous candidiasis syndrome; autoimmune polyendocrinopathy caused by mutation in aire; Autoimmune Polyglandular Syndrome Type 1; aire autoimmune polyendocrinopathy; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome; multiple endocrine deficiency-Addison disease-candidiasis syndrome; autoimmune polyendocrinopathy caused by mutation in AIRE; autoimmune polyendocrine syndrome type 1; APS type 1; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; autoimmune hypoparathyroidism-chronic candidiasis-Addison disease syndrome; APS1; AIRE autoimmune polyendocrinopathy; ham syndrome; Whitaker syndrom
• Definition: Autoimmune polyendocrinopathy type 1, or APECED syndrome, is a genetic disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.
• Disease Hierarchy:
  DIS7K8TV: Hereditary hypoparathyroidism
  DISOLDB2: Autoimmune polyendocrinopathy
  DISFS818: Adrenal gland disorder
  DISPBPEO: Autoimmune hypoparathyroidism
  DISWJP8J: Autoimmune polyendocrine syndrome type 1
• Disease Identifiers:
  MONDO ID: MONDO_0009411
  MESH ID: D016884
  UMLS CUI: C0085859
  OMIM ID: 240300
  MedGen ID: 39125
  Orphanet ID: 3453
  SNOMED CT ID: 11244009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Fluconazole	DMOWZ6B	Approved	Small molecular drug	[1]
Nystatin	DM63QS9	Approved	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TH	TTUHP71	Limited	Biomarker	[3]
CYP1A2	TTS1DTU	moderate	Biomarker	[4]
EGLN2	TTMHFRY	moderate	Biomarker	[5]
HDC	TTV9GOF	moderate	Biomarker	[6]
ADH1A	TT5AHZ0	Strong	Altered Expression	[7]
ECE2	TT5U914	Strong	Biomarker	[8]
GNA11	TTSRXJW	Strong	Biomarker	[9]
CBLB	TTHRAIJ	Definitive	Biomarker	[10]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BPIFB1	OTOZYJMO	Limited	Biomarker	[11]
CFAP410	OTJ94J99	moderate	Biomarker	[12]
NUDT11	OTFDXJA1	moderate	Biomarker	[13]
PTRH1	OTOAOS93	moderate	Genetic Variation	[14]
RO60	OTLGM5A8	moderate	Genetic Variation	[15]
TMPRSS3	OT0GTO1Z	moderate	Genetic Variation	[12]
CDR2	OTD3ZJST	Strong	Biomarker	[7]
DLAT	OT9LBJVN	Strong	Biomarker	[16]
NLRP5	OTLU1YML	Strong	Genetic Variation	[17]
NUDT10	OT61XMYC	Strong	Biomarker	[18]
TBCE	OTGBSTKS	Strong	Biomarker	[9]
TSGA10	OTIF1O1T	Strong	Biomarker	[19]
AIRE	OTA7G1Y1	Definitive	Autosomal recessive	[20]

References

• [1] Fluconazole FDA Label
• [2] Nystatin FDA Label
• [3] Reduction of Total Brain and Cerebellum Volumes Associated With Neuronal Autoantibodies in Patients With APECED.J Clin Endocrinol Metab. 2019 Jan 1;104(1):150-162. doi: 10.1210/jc.2018-01313.
• [4] Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1.Gastroenterology. 1998 Feb;114(2):324-8. doi: 10.1016/s0016-5085(98)70484-6.
• [5] Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.Immunity. 2015 Jun 16;42(6):1185-96. doi: 10.1016/j.immuni.2015.04.021.
• [6] Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells.J Clin Endocrinol Metab. 2003 Apr;88(4):1445-52. doi: 10.1210/jc.2002-021761.
• [7] ADH1 expression inversely correlates with CDR1 and CDR2 in Candida albicans from chronic oral candidosis in APECED (APS-I) patients.FEMS Yeast Res. 2011 Sep;11(6):494-8. doi: 10.1111/j.1567-1364.2011.00739.x. Epub 2011 Jun 16.
• [8] Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1.Autoimmunity. 2017 Jun;50(4):223-231. doi: 10.1080/08916934.2017.1332183. Epub 2017 May 30.
• [9] Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism.J Clin Endocrinol Metab. 2014 Mar;99(3):E469-73. doi: 10.1210/jc.2013-3136. Epub 2014 Jan 1.
• [10] T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency.Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14709-14. doi: 10.1073/pnas.1009209107. Epub 2010 Jul 28.
• [11] BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.Sci Transl Med. 2013 Oct 9;5(206):206ra139. doi: 10.1126/scitranslmed.3006998.
• [12] Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis.Genomics. 1998 Jan 1;47(1):64-70. doi: 10.1006/geno.1997.5066.
• [13] Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-.J Vis Exp. 2018 Jun 14;(136):57421. doi: 10.3791/57421.
• [14] Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.J Pediatr. 2018 Dec;203:391-399.e1. doi: 10.1016/j.jpeds.2018.08.010.
• [15] Profiling Autoantibodies against Salivary Proteins in Sicca Conditions.J Dent Res. 2019 Jul;98(7):772-778. doi: 10.1177/0022034519850564. Epub 2019 May 16.
• [16] Recent developments in autoimmune liver diseases.J Gastroenterol Hepatol. 1997 Oct;12(9-10):S256-71. doi: 10.1111/j.1440-1746.1997.tb00509.x.
• [17] Autoimmune oophoritis with multiple molecular targets mitigated by transgenic expression of mater.Endocrinology. 2011 Jun;152(6):2465-73. doi: 10.1210/en.2011-0022. Epub 2011 Mar 29.
• [18] The natural history of autoimmune Addison's disease from the detection of autoantibodies to development of the disease: a long-term follow-up study on 143 patients.Eur J Endocrinol. 2019 Mar;180(3):223-234. doi: 10.1530/EJE-18-0313.
• [19] TSGA10 - A target for autoantibodies in autoimmune polyendocrine syndrome type 1 and systemic lupus erythematosus.Scand J Immunol. 2011 Feb;73(2):147-53. doi: 10.1111/j.1365-3083.2010.02486.x.
• [20] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.